👪

Inheritance

1

Autosomal recessive HP:0000007

Disease requires biallelic DNAH10 variants: homozygous frameshift, homozygous missense and compound heterozygous missense genotypes in Chinese and Pakistani men.

Autosomal recessive inheritance

Show evidence (2 references)

PMID:39996363 SUPPORT Human Clinical

"Sanger sequencing revealed that these variants follow an autosomal recessive mode of inheritance."

Recessive segregation in two Pakistani families.

CGGV:assertion_0128b225-6f43-4ed2-b111-a50dde1b25e5-2026-05-07T190000.000Z SUPPORT Other

"DNAH10, Spermatogenic Failure 56 (MONDO:0030430), autosomal recessive"

ClinGen curates the relationship as autosomal recessive.

◈

Mechanistic Hypotheses

1

DNAH10 loss is usually limited to the sperm flagellum but can also cause primary ciliary dyskinesia

dnah10_sperm_vs_motile_cilia_spectrum EMERGING

Evidence balance 1 support 3 refute

Most men with SPGF56 have no reported respiratory or laterality symptoms, yet one homozygous DNAH10 missense patient had full primary ciliary dyskinesia with asthenoteratozoospermia, and Dnah10 knockout and knock-in mice develop respiratory infection and hydrocephalus. Whether allele type, residual function or incomplete ciliary assessment explains the difference is unresolved; none of the SPGF56 cohorts reports systematic ciliary testing.

Show evidence (4 references)

PMID:39996363 SUPPORT Human Clinical

"causing asthenoteratozoospermia with MMAF without PCD symptoms in patients from two unrelated Pakistani families"

Sperm-restricted disease in two families.

PMID:37314648 REFUTE Human Clinical

"The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia."

A DNAH10 patient with both sperm and motile cilia disease contradicts a strictly sperm-restricted requirement.

PMID:37314648 REFUTE Model Organism

"Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus"

The knockout mice have ciliary disease as well as infertility.

+ 1 more reference

⚙

Pathophysiology

5

Loss of the DNAH10 Inner-Arm Dynein Heavy Chain

Biallelic frameshift and missense variants abolish or sharply reduce DNAH10 along the sperm flagellum. DNAH10 is one of the three heavy chains of the double-headed inner dynein arm f (IDA f / I1), with DNAH2 and DNAH12.

DNAH10 hgnc:2941

minus-end-directed microtubule motor activity GO:0008569 ↓ DECREASED

Inner dynein arm GO:0036156

Downstream

Co-Depletion of Inner-Arm Dynein Heavy Chains from the Sperm Flagellum Without DNAH10, its inner-arm partners are lost from the flagellum.

Impaired Intramanchette Transport During Spermiogenesis Shown in a mouse study; DNAH10 is proposed to bridge UCHL3 and PACRG in the manchette, but how this relates to its axonemal role is unclear.

Show evidence (3 references)

PMID:34237282 SUPPORT Human Clinical

"spermatozoa from the men harboring bi-allelic DNAH10 variants exhibited an absence or markedly reduced staining intensity of DNAH10 and other IDA components, including DNAH2 and DNAH6"

Loss of DNAH10 protein from patient sperm.

PMID:39996363 SUPPORT Human Clinical

"immunofluorescence staining revealed loss of DNAH10 protein signals along sperm flagella"

Independent confirmation in Pakistani patients carrying missense variants.

PMID:40898283 SUPPORT Computational

"The IDAf complex comprises intermediate chains (DNAI3, DNAI4, DNAI7), light chains (DYNLRB1, DYNRB2, DYNLL1), and heavy chains (DNAH2, DNAH10, DNAH12)."

Analysis of published cryo-EM axoneme structures places DNAH10 as a heavy chain of IDA f.

Co-Depletion of Inner-Arm Dynein Heavy Chains from the Sperm Flagellum

Patient sperm lose the inner-arm heavy chains DNAH2 and DNAH6 (and in a second cohort DNAH1) along with DNAH10, indicating that DNAH10 is needed for these inner-arm dyneins to assemble in or remain in the axoneme.

Inner dynein arm assembly GO:0036159 ↓ DECREASED

Downstream

Inner Dynein Arm Loss in the Sperm Axoneme

Show evidence (3 references)

PMID:34237282 SUPPORT Human Clinical

"spermatozoa from the men harboring bi-allelic DNAH10 variants exhibited an absence or markedly reduced staining intensity of DNAH10 and other IDA components, including DNAH2 and DNAH6"

Co-loss of DNAH2 and DNAH6 in patient sperm.

PMID:34657236 SUPPORT Human Clinical

"Using immunofluorescence assays, we found a significant reduction in IDA-related proteins including DNAH10 and DNAH1."

Co-loss of DNAH1 in a second cohort.

PMID:40592014 SUPPORT Human Clinical

"indicated a possible interaction between DNAH2 and DNAH10"

Immunofluorescence in a pooled cohort suggests DNAH2 and DNAH10 depend on each other.

Inner Dynein Arm Loss in the Sperm Axoneme

Electron microscopy of patient sperm shows absent or markedly deficient inner dynein arms and a disorganized flagellum.

Sperm CL:0000019

Axoneme GO:0005930 Sperm flagellum GO:0036126

Downstream

Multiple Morphological Abnormalities of the Sperm Flagella

Show evidence (2 references)

PMID:34237282 SUPPORT Human Clinical

"Morphological and ultrastructural analyses of the spermatozoa obtained from men harboring bi-allelic DNAH10 variants revealed striking flagellar defects with the absence of inner dynein arms (IDAs)."

Ultrastructural loss of inner dynein arms in patient sperm.

PMID:34657236 SUPPORT Human Clinical

"ultrastructural analysis by transmission electron microscopy showed significant inner dynein arm (IDA) deficiency in sperm flagella"

Independent confirmation of inner-arm deficiency.

Impaired Intramanchette Transport During Spermiogenesis

In DNAH10-deficient spermatids the manchette functions abnormally and axonemal proteins are mislocalized. DNAH10 enhances binding between the deubiquitinase UCHL3 and PACRG, which UCHL3 stabilizes. The study is indexed with Mice and Humans in MeSH; the abstract does not say which observations come from which species, and this route has not been shown in patient tissue.

Spermatid CL:0000018

Intramanchette transport GO:1990953 ↓ DECREASED

Manchette GO:0002177

Downstream

Abnormal sperm head morphology The manchette shapes the spermatid nucleus, so manchette dysfunction gives misshapen sperm heads.

Multiple Morphological Abnormalities of the Sperm Flagella Mislocalized axonemal proteins may add to the flagellar defect.

Show evidence (2 references)

PMID:41058558 SUPPORT Model Organism

"Additionally, DNAH10 dysfunction leads to impaired manchette function and aberrant localisation of axonemal proteins."

Manchette dysfunction in DNAH10 deficiency (MeSH-indexed mouse study).

PMID:41058558 SUPPORT In Vitro

"In this process, DNAH10 exerts a bridging effect, enhancing the interaction between the UCHL3-PACRG complex to facilitate their involvement in manchette function."

Proposed molecular basis of the manchette role.

Multiple Morphological Abnormalities of the Sperm Flagella

The defining semen phenotype: absent, short, coiled, bent and irregular-caliber flagella in the same ejaculate, frequently with abnormal heads.

Sperm CL:0000019

Sperm axoneme assembly GO:0007288 ↓ DECREASED

Animal models

Dnah10 knockout and knock-in mice Mouse recapitulates The mutant mice reproduce the human sperm phenotype.

Downstream

Reduced sperm motility

Male infertility Malformed, poorly motile sperm cannot reach or fertilize the oocyte in vivo.

Absent sperm flagella

Short sperm flagella

Coiled sperm flagella

Irregularly shaped sperm tail

Show evidence (2 references)

PMID:34237282 SUPPORT Human Clinical

"Bi-allelic DNAH10 variants were identified in five individuals with MMAF from four unrelated families."

MMAF in DNAH10 patients.

PMID:39996363 SUPPORT Human Clinical

"These patients’ spermatozoa exhibited a high percentage of flagellar defects, and more than half had abnormal head morphology (>50%)."

Flagellar and head defects in Pakistani patients.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

7

Male infertility Reproductive HP:0003251

Show evidence (1 reference)

PMID:34237282 SUPPORT Human Clinical

"deleterious bi-allelic DNAH10 variants can cause male infertility with MMAF"

Male infertility in DNAH10 patients.

Reduced sperm motility Reproductive HP:0012207

Show evidence (2 references)

PMID:39996363 SUPPORT Human Clinical

"However, more than 80% of their sperm were immotile"

Most sperm immotile.

PMID:39996363 SUPPORT BACKGROUND Human Clinical

"the sperm was completely immotile, whereas about 10% of sperm from the other patients were motile"

The authors' summary of earlier reports, which found complete immotility in two homozygous patients.

Absent sperm flagella Reproductive HP:0032558

Show evidence (1 reference)

CGGV:assertion_0128b225-6f43-4ed2-b111-a50dde1b25e5-2026-05-07T190000.000Z SUPPORT REVIEW SYNTHESIS Other

"Some of the most common patient phenotypes are: Male infertility, Immotile sperm, Abnormal sperm morphology, Short sperm flagella, Absent sperm flagella, Coiled sperm flagella, Irregularly shaped sperm tail"

ClinGen's summary of the phenotypes of curated probands.

Short sperm flagella Reproductive HP:0032559

Show evidence (1 reference)

PMID:39996363 SUPPORT Human Clinical

"also exhibited a significant increase in the number of short sperm flagella, compared to the fertile control group"

Excess short flagella in two patients.

Coiled sperm flagella Reproductive HP:0032560

Show evidence (1 reference)

PMID:39996363 SUPPORT Human Clinical

"the three patients showed significantly higher percentages of coiled (>30%)"

Coiled flagella in all three patients.

Irregularly shaped sperm tail Reproductive HP:0033393

Show evidence (1 reference)

CGGV:assertion_0128b225-6f43-4ed2-b111-a50dde1b25e5-2026-05-07T190000.000Z SUPPORT REVIEW SYNTHESIS Other

"Some of the most common patient phenotypes are: Male infertility, Immotile sperm, Abnormal sperm morphology, Short sperm flagella, Absent sperm flagella, Coiled sperm flagella, Irregularly shaped sperm tail"

ClinGen's summary of the phenotypes of curated probands.

Abnormal sperm head morphology Reproductive HP:0012865

Show evidence (1 reference)

PMID:39996363 SUPPORT Human Clinical

"the sperm heads were abnormal, mainly pyriform and tapered"

Head defects in patient sperm.

🧬

Genetic Associations

1

DNAH10 (Causal)

Gene: DNAH10 hgnc:2941 gene page

Show evidence (3 references)

PMID:34237282 SUPPORT Human Clinical

"Bi-allelic DNAH10 variants were identified in five individuals with MMAF from four unrelated families."

Primary gene-disease report from a 643-man MMAF cohort.

PMID:34657236 SUPPORT Human Clinical

"We found one homozygous frameshift DNAH10 variant (NM_207437: c.2514delG:p.L839*) and one compound heterozygous DNAH10 variant"

Independent replication.

PMID:39996363 SUPPORT Human Clinical

"we identified two novel compound heterozygous variants in the gene, dynein axonemal heavy chain 10 ( DNAH10 ), in three patients from two unrelated Pakistani families"

Replication in a different ancestry.

💊

Medical Actions

1

Intracytoplasmic Sperm Injection

Action: Intracytoplasmic Sperm Injection NCIT:C185482

Platform: Other

ICSI bypasses the motility and form defect and restores fertilization in DNAH10 deficiency. A pooled DNAH2/DNAH6/DNAH10 cohort reported live births in five of six couples. Numbers are small.

Mechanism Target:

Multiple Morphological Abnormalities of the Sperm Flagella — Direct injection makes flagellar propulsion and form irrelevant to fertilization.

Show evidence (1 reference)

PMID:42522280 SUPPORT Human Clinical

"ICSI restored fertilization in DNAH10/DNAH12 deficiency"

Human case series showing ICSI success in DNAH10 deficiency.

Show evidence (1 reference)

PMID:40592014 SUPPORT Human Clinical

"Moreover, five out of six affected couples achieved a live birth via intracytoplasmic sperm injection (ICSI)."

Live births in a cohort pooling DNAH2, DNAH6 and DNAH10 patients.

🐁

Animal Models

1

Dnah10 knockout and knock-in mice

Mice lacking Dnah10 or carrying a patient-derived missense variant reproduce male infertility with MMAF. A later study of knockout and knock-in mice reported primary ciliary dyskinesia features as well.

Species

Mouse

Genotype

Dnah10 knockout, or knock-in of a patient missense variant, homozygous

Publication

PMID:34237282

Pathograph links

Multiple Morphological Abnormalities of the Sperm Flagella recapitulates fidelity: high The mutant mice reproduce the human sperm phenotype.

Limitations: The mice also develop chronic respiratory infection and hydrocephalus, whereas most men with SPGF56 have no reported ciliary symptoms, so the model has a broader phenotype than most patients.

Show evidence (2 references)

PMID:34237282 SUPPORT Model Organism

"the phenotypes were recapitulated in mouse models lacking Dnah10 or expressing a disease-associated variant, confirming the involvement of DNAH10 in human MMAF"

Authors' statement that the mice recapitulate MMAF.

+ 1 more reference

{ }

Source YAML

click to show

name: Spermatogenic Failure 56
creation_date: "2026-10-14T00:00:00Z"
category: Mendelian
synonyms:
- SPGF56
- spermatogenic failure 56
- DNAH10-related asthenoteratozoospermia
- DNAH10-related multiple morphological abnormalities of the sperm flagella
description: >-
  Spermatogenic failure 56 (SPGF56) is autosomal recessive male infertility
  caused by biallelic variants in DNAH10, which encodes an axonemal inner
  dynein arm heavy chain expressed mainly in the testis. Structural studies
  place DNAH10 in the double-headed inner dynein arm f (IDA f, also called
  I1) together with the heavy chains DNAH2 and DNAH12. Affected men have
  asthenoteratozoospermia with multiple morphological abnormalities of the
  sperm flagella (MMAF): absent, short, coiled and irregular flagella, often
  with misshapen (pyriform or tapered) heads. Patient sperm lack inner dynein
  arms and lose DNAH10 together with other inner-arm heavy chains (DNAH1,
  DNAH2, DNAH6).

  Dnah10 knockout and knock-in mice reproduce male infertility and MMAF, and
  in mice DNAH10 also bridges the UCHL3-PACRG complex during
  intramanchette transport, which may explain the head defects. Most
  reported men have no respiratory symptoms, but biallelic DNAH10 variants
  have also been reported with primary ciliary dyskinesia, and the knockout
  mice show ciliary disease, so SPGF56 lies on a spectrum with DNAH10-related
  primary ciliary dyskinesia. ICSI restores fertilization and has given live
  births.
disease_term:
  preferred_term: spermatogenic failure 56
  term:
    id: MONDO:0030430
    label: spermatogenic failure 56
parents:
- Spermatogenic Failure
- Genetic Disease
notes: >-
  MONDO cross-references this disease as OMIM 619515. ClinGen splits
  DNAH10-related disease into two curations, spermatogenic failure 56
  (Moderate) and primary ciliary dyskinesia (Limited); the SPGF56 curation
  counts the PCD proband of PMID:37314648 among its eight probands, so the
  two entities overlap in the source data. PMID:40592014 reports DNAH2,
  DNAH6 and DNAH10 patients together, and its abstract does not separate
  their ICSI results by gene. A single oligoasthenoteratozoospermia patient
  carrying homozygous missense variants in both SUN5 and DNAH10
  (PMID:40373254) is not used, because the SUN5 variant is the likelier
  explanation for its head-tail coupling defect. Abstract-only caches:
  PMID:34237282, PMID:34657236, PMID:37314648, PMID:41058558 and
  PMID:40592014.
inheritance:
- name: Autosomal recessive
  description: >-
    Disease requires biallelic DNAH10 variants: homozygous frameshift,
    homozygous missense and compound heterozygous missense genotypes in
    Chinese and Pakistani men.
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: PMID:39996363
    reference_title: "Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sanger sequencing revealed that these variants follow an autosomal recessive mode of inheritance."
    explanation: Recessive segregation in two Pakistani families.
  - reference: CGGV:assertion_0128b225-6f43-4ed2-b111-a50dde1b25e5-2026-05-07T190000.000Z
    reference_title: "DNAH10 / spermatogenic failure 56 (Moderate)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "DNAH10, Spermatogenic Failure 56 (MONDO:0030430), autosomal recessive"
    explanation: ClinGen curates the relationship as autosomal recessive.
pathophysiology:
- name: Loss of the DNAH10 Inner-Arm Dynein Heavy Chain
  description: >-
    Biallelic frameshift and missense variants abolish or sharply reduce
    DNAH10 along the sperm flagellum. DNAH10 is one of the three heavy chains
    of the double-headed inner dynein arm f (IDA f / I1), with DNAH2 and
    DNAH12.
  biological_scale: MOLECULAR
  genes:
  - preferred_term: DNAH10
    term:
      id: hgnc:2941
      label: DNAH10
  molecular_functions:
  - preferred_term: minus-end-directed microtubule motor activity
    modifier: DECREASED
    term:
      id: GO:0008569
      label: minus-end-directed microtubule motor activity
  cellular_components:
  - preferred_term: Inner dynein arm
    term:
      id: GO:0036156
      label: inner dynein arm
  downstream:
  - target: Co-Depletion of Inner-Arm Dynein Heavy Chains from the Sperm Flagellum
    causal_link_type: DIRECT
    description: Without DNAH10, its inner-arm partners are lost from the flagellum.
  - target: Impaired Intramanchette Transport During Spermiogenesis
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Shown in a mouse study; DNAH10 is proposed to bridge UCHL3 and PACRG
      in the manchette, but how this relates to its axonemal role is unclear.
  evidence:
  - reference: PMID:34237282
    reference_title: "Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "spermatozoa from the men harboring bi-allelic DNAH10 variants exhibited an absence or markedly reduced staining intensity of DNAH10 and other IDA components, including DNAH2 and DNAH6"
    explanation: Loss of DNAH10 protein from patient sperm.
  - reference: PMID:39996363
    reference_title: "Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "immunofluorescence staining revealed loss of DNAH10 protein signals along sperm flagella"
    explanation: Independent confirmation in Pakistani patients carrying missense variants.
  - reference: PMID:40898283
    reference_title: "DNAH10 mutation cause primary ciliary dyskinesia with defects of IDAf complex assembly and lung fibrosis manifestation."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "The IDAf complex comprises intermediate chains (DNAI3, DNAI4, DNAI7), light chains (DYNLRB1, DYNRB2, DYNLL1), and heavy chains (DNAH2, DNAH10, DNAH12)."
    explanation: Analysis of published cryo-EM axoneme structures places DNAH10 as a heavy chain of IDA f.
- name: Co-Depletion of Inner-Arm Dynein Heavy Chains from the Sperm Flagellum
  description: >-
    Patient sperm lose the inner-arm heavy chains DNAH2 and DNAH6 (and in a
    second cohort DNAH1) along with DNAH10, indicating that DNAH10 is needed
    for these inner-arm dyneins to assemble in or remain in the axoneme.
  biological_scale: MOLECULAR
  biological_processes:
  - preferred_term: Inner dynein arm assembly
    term:
      id: GO:0036159
      label: inner dynein arm assembly
    modifier: DECREASED
  downstream:
  - target: Inner Dynein Arm Loss in the Sperm Axoneme
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:34237282
    reference_title: "Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "spermatozoa from the men harboring bi-allelic DNAH10 variants exhibited an absence or markedly reduced staining intensity of DNAH10 and other IDA components, including DNAH2 and DNAH6"
    explanation: Co-loss of DNAH2 and DNAH6 in patient sperm.
  - reference: PMID:34657236
    reference_title: "Bi-allelic variants in DNAH10 cause asthenoteratozoospermia and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Using immunofluorescence assays, we found a significant reduction in IDA-related proteins including DNAH10 and DNAH1."
    explanation: Co-loss of DNAH1 in a second cohort.
  - reference: PMID:40592014
    reference_title: "Patients with mutations in DNAH2, DNAH6 and DNAH10 causing multiple morphological abnormalities of human sperm flagella achieve good ICSI outcomes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "indicated a possible interaction between DNAH2 and DNAH10"
    explanation: Immunofluorescence in a pooled cohort suggests DNAH2 and DNAH10 depend on each other.
- name: Inner Dynein Arm Loss in the Sperm Axoneme
  description: >-
    Electron microscopy of patient sperm shows absent or markedly deficient
    inner dynein arms and a disorganized flagellum.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: Sperm
    term:
      id: CL:0000019
      label: sperm
  cellular_components:
  - preferred_term: Axoneme
    term:
      id: GO:0005930
      label: axoneme
  - preferred_term: Sperm flagellum
    term:
      id: GO:0036126
      label: sperm flagellum
  downstream:
  - target: Multiple Morphological Abnormalities of the Sperm Flagella
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:34237282
    reference_title: "Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Morphological and ultrastructural analyses of the spermatozoa obtained from men harboring bi-allelic DNAH10 variants revealed striking flagellar defects with the absence of inner dynein arms (IDAs)."
    explanation: Ultrastructural loss of inner dynein arms in patient sperm.
  - reference: PMID:34657236
    reference_title: "Bi-allelic variants in DNAH10 cause asthenoteratozoospermia and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "ultrastructural analysis by transmission electron microscopy showed significant inner dynein arm (IDA) deficiency in sperm flagella"
    explanation: Independent confirmation of inner-arm deficiency.
- name: Impaired Intramanchette Transport During Spermiogenesis
  description: >-
    In DNAH10-deficient spermatids the manchette functions abnormally and
    axonemal proteins are mislocalized. DNAH10 enhances binding between
    the deubiquitinase UCHL3 and PACRG, which UCHL3 stabilizes. The study is
    indexed with Mice and Humans in MeSH; the abstract does not say which
    observations come from which species, and this route has not been shown
    in patient tissue.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: Spermatid
    term:
      id: CL:0000018
      label: spermatid
  cellular_components:
  - preferred_term: Manchette
    term:
      id: GO:0002177
      label: manchette
  biological_processes:
  - preferred_term: Intramanchette transport
    term:
      id: GO:1990953
      label: intramanchette transport
    modifier: DECREASED
  downstream:
  - target: Abnormal sperm head morphology
    causal_link_type: DIRECT
    description: The manchette shapes the spermatid nucleus, so manchette dysfunction gives misshapen sperm heads.
    evidence:
    - reference: PMID:41058558
      reference_title: "DNAH10 interacts with UCHL3-PACRG complex to coordinate sperm head and flagella development during spermiogenesis."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "we demonstrated that DNAH10 deficiency leads to abnormal morphology of the sperm head and flagella"
      explanation: Links DNAH10 deficiency to head as well as flagellar defects.
  - target: Multiple Morphological Abnormalities of the Sperm Flagella
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Mislocalized axonemal proteins may add to the flagellar defect.
  evidence:
  - reference: PMID:41058558
    reference_title: "DNAH10 interacts with UCHL3-PACRG complex to coordinate sperm head and flagella development during spermiogenesis."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Additionally, DNAH10 dysfunction leads to impaired manchette function and aberrant localisation of axonemal proteins."
    explanation: Manchette dysfunction in DNAH10 deficiency (MeSH-indexed mouse study).
  - reference: PMID:41058558
    reference_title: "DNAH10 interacts with UCHL3-PACRG complex to coordinate sperm head and flagella development during spermiogenesis."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "In this process, DNAH10 exerts a bridging effect, enhancing the interaction between the UCHL3-PACRG complex to facilitate their involvement in manchette function."
    explanation: Proposed molecular basis of the manchette role.
- name: Multiple Morphological Abnormalities of the Sperm Flagella
  description: >-
    The defining semen phenotype: absent, short, coiled, bent and
    irregular-caliber flagella in the same ejaculate, frequently with
    abnormal heads.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: Sperm
    term:
      id: CL:0000019
      label: sperm
  biological_processes:
  - preferred_term: Sperm axoneme assembly
    term:
      id: GO:0007288
      label: sperm axoneme assembly
    modifier: DECREASED
  downstream:
  - target: Reduced sperm motility
    causal_link_type: DIRECT
  - target: Male infertility
    causal_link_type: DIRECT
    description: Malformed, poorly motile sperm cannot reach or fertilize the oocyte in vivo.
  - target: Absent sperm flagella
    causal_link_type: DIRECT
  - target: Short sperm flagella
    causal_link_type: DIRECT
  - target: Coiled sperm flagella
    causal_link_type: DIRECT
  - target: Irregularly shaped sperm tail
    causal_link_type: DIRECT
  evidence:
  - reference: PMID:34237282
    reference_title: "Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Bi-allelic DNAH10 variants were identified in five individuals with MMAF from four unrelated families."
    explanation: MMAF in DNAH10 patients.
  - reference: PMID:39996363
    reference_title: "Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "These patients’ spermatozoa exhibited a high percentage of flagellar defects, and more than half had abnormal head morphology (>50%)."
    explanation: Flagellar and head defects in Pakistani patients.
mechanistic_hypotheses:
- hypothesis_group_id: dnah10_sperm_vs_motile_cilia_spectrum
  hypothesis_label: DNAH10 loss is usually limited to the sperm flagellum but can also cause primary ciliary dyskinesia
  status: EMERGING
  description: >-
    Most men with SPGF56 have no reported respiratory or laterality
    symptoms, yet one homozygous DNAH10 missense patient had full primary
    ciliary dyskinesia with asthenoteratozoospermia, and Dnah10 knockout and
    knock-in mice develop respiratory infection and hydrocephalus. Whether
    allele type, residual function or incomplete ciliary assessment explains
    the difference is unresolved; none of the SPGF56 cohorts reports
    systematic ciliary testing.
  evidence:
  - reference: PMID:39996363
    reference_title: "Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "causing asthenoteratozoospermia with MMAF without PCD symptoms in patients from two unrelated Pakistani families"
    explanation: Sperm-restricted disease in two families.
  - reference: PMID:37314648
    reference_title: "Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice."
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia."
    explanation: A DNAH10 patient with both sperm and motile cilia disease contradicts a strictly sperm-restricted requirement.
  - reference: PMID:37314648
    reference_title: "Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice."
    supports: REFUTE
    evidence_source: MODEL_ORGANISM
    snippet: "Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus"
    explanation: The knockout mice have ciliary disease as well as infertility.
  - reference: PMID:40898283
    reference_title: "DNAH10 mutation cause primary ciliary dyskinesia with defects of IDAf complex assembly and lung fibrosis manifestation."
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: "we demonstrated the presence of loss-of-function mutations in the DNAH10 gene among two families affected by primary ciliary dyskinesia"
    explanation: A second report of DNAH10 loss of function in families with respiratory PCD, against a sperm-restricted requirement.
phenotypes:
- category: Reproductive
  name: Male infertility
  description: Primary male infertility is the presenting complaint.
  phenotype_term:
    preferred_term: Male infertility
    term:
      id: HP:0003251
      label: Male infertility
  evidence:
  - reference: PMID:34237282
    reference_title: "Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "deleterious bi-allelic DNAH10 variants can cause male infertility with MMAF"
    explanation: Male infertility in DNAH10 patients.
- category: Reproductive
  name: Reduced sperm motility
  description: >-
    Severe asthenozoospermia. Sperm from the two homozygous patients of the
    first reports were completely immotile; about 10-20% of sperm were
    motile in compound heterozygous patients.
  phenotype_term:
    preferred_term: Severe asthenozoospermia
    term:
      id: HP:0012207
      label: Reduced sperm motility
  evidence:
  - reference: PMID:39996363
    reference_title: "Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "However, more than 80% of their sperm were immotile"
    explanation: Most sperm immotile.
  - reference: PMID:39996363
    reference_title: "Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: "the sperm was completely immotile, whereas about 10% of sperm from the other patients were motile"
    explanation: The authors' summary of earlier reports, which found complete immotility in two homozygous patients.
- category: Reproductive
  name: Absent sperm flagella
  description: Flagellum-less sperm are part of the MMAF mosaic.
  phenotype_term:
    preferred_term: Absent sperm flagella
    term:
      id: HP:0032558
      label: Absent sperm flagella
  evidence:
  - reference: CGGV:assertion_0128b225-6f43-4ed2-b111-a50dde1b25e5-2026-05-07T190000.000Z
    reference_title: "DNAH10 / spermatogenic failure 56 (Moderate)"
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "Some of the most common patient phenotypes are: Male infertility, Immotile sperm, Abnormal sperm morphology, Short sperm flagella, Absent sperm flagella, Coiled sperm flagella, Irregularly shaped sperm tail"
    explanation: ClinGen's summary of the phenotypes of curated probands.
- category: Reproductive
  name: Short sperm flagella
  description: Short flagella are part of the MMAF mosaic.
  phenotype_term:
    preferred_term: Short sperm flagella
    term:
      id: HP:0032559
      label: Short sperm flagella
  evidence:
  - reference: PMID:39996363
    reference_title: "Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "also exhibited a significant increase in the number of short sperm flagella, compared to the fertile control group"
    explanation: Excess short flagella in two patients.
- category: Reproductive
  name: Coiled sperm flagella
  description: Coiled flagella exceed 30% of sperm in the Pakistani patients.
  phenotype_term:
    preferred_term: Coiled sperm flagella
    term:
      id: HP:0032560
      label: Coiled sperm flagella
  evidence:
  - reference: PMID:39996363
    reference_title: "Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the three patients showed significantly higher percentages of coiled (>30%)"
    explanation: Coiled flagella in all three patients.
- category: Reproductive
  name: Irregularly shaped sperm tail
  description: Irregular-caliber flagella are part of the MMAF mosaic.
  phenotype_term:
    preferred_term: Irregular-caliber sperm flagella
    term:
      id: HP:0033393
      label: Irregularly shaped sperm tail
  evidence:
  - reference: CGGV:assertion_0128b225-6f43-4ed2-b111-a50dde1b25e5-2026-05-07T190000.000Z
    reference_title: "DNAH10 / spermatogenic failure 56 (Moderate)"
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: "Some of the most common patient phenotypes are: Male infertility, Immotile sperm, Abnormal sperm morphology, Short sperm flagella, Absent sperm flagella, Coiled sperm flagella, Irregularly shaped sperm tail"
    explanation: ClinGen's summary of the phenotypes of curated probands.
- category: Reproductive
  name: Abnormal sperm head morphology
  description: >-
    More than half of sperm had abnormal, mainly pyriform or tapered, heads
    in the Pakistani patients. In mouse studies the head defect follows
    manchette dysfunction.
  phenotype_term:
    preferred_term: Abnormal sperm head morphology
    term:
      id: HP:0012865
      label: Abnormal sperm head morphology
  evidence:
  - reference: PMID:39996363
    reference_title: "Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the sperm heads were abnormal, mainly pyriform and tapered"
    explanation: Head defects in patient sperm.
genetic:
- name: DNAH10
  association: Causal
  gene_term:
    preferred_term: DNAH10
    term:
      id: hgnc:2941
      label: DNAH10
  gene_disease_validity:
  - validity_classification: MODERATE
    classified_by: CLINGEN
    external_id: CGGV:assertion_0128b225-6f43-4ed2-b111-a50dde1b25e5-2026-05-07T190000.000Z
    evidence:
    - reference: CGGV:assertion_0128b225-6f43-4ed2-b111-a50dde1b25e5-2026-05-07T190000.000Z
      reference_title: "DNAH10 / spermatogenic failure 56 (Moderate)"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "DNAH10 | HGNC:2941 | spermatogenic failure 56 | MONDO:0030430 | AR | Moderate"
      explanation: ClinGen Motile Ciliopathy GCEP classifies DNAH10-SPGF56 as Moderate, autosomal recessive.
  notes: >-
    Reported alleles include homozygous frameshift p.L839Ter (NM_207437
    c.2514delG), compound heterozygous missense p.M3607T/p.T4231I
    (PMID:34657236), and compound heterozygous missense p.P3137T/p.D4316H and
    p.G2950D/p.R3687W in Pakistani families (PMID:39996363). ClinGen
    separately classifies DNAH10 and primary ciliary dyskinesia as Limited.
  evidence:
  - reference: PMID:34237282
    reference_title: "Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Bi-allelic DNAH10 variants were identified in five individuals with MMAF from four unrelated families."
    explanation: Primary gene-disease report from a 643-man MMAF cohort.
  - reference: PMID:34657236
    reference_title: "Bi-allelic variants in DNAH10 cause asthenoteratozoospermia and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We found one homozygous frameshift DNAH10 variant (NM_207437: c.2514delG:p.L839*) and one compound heterozygous DNAH10 variant"
    explanation: Independent replication.
  - reference: PMID:39996363
    reference_title: "Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "we identified two novel compound heterozygous variants in the gene, dynein axonemal heavy chain 10 ( DNAH10 ), in three patients from two unrelated Pakistani families"
    explanation: Replication in a different ancestry.
animal_models:
- name: Dnah10 knockout and knock-in mice
  species: Mouse
  genotype: Dnah10 knockout, or knock-in of a patient missense variant, homozygous
  publication: PMID:34237282
  description: >-
    Mice lacking Dnah10 or carrying a patient-derived missense variant
    reproduce male infertility with MMAF. A later study of knockout and
    knock-in mice reported primary ciliary dyskinesia features as well.
  modeled_mechanisms:
  - target: Multiple Morphological Abnormalities of the Sperm Flagella
    relationship: RECAPITULATES
    fidelity: HIGH
    description: The mutant mice reproduce the human sperm phenotype.
    limitations: >-
      The mice also develop chronic respiratory infection and hydrocephalus,
      whereas most men with SPGF56 have no reported ciliary symptoms, so the
      model has a broader phenotype than most patients.
    evidence:
    - reference: PMID:34237282
      reference_title: "Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "the phenotypes were recapitulated in mouse models lacking Dnah10 or expressing a disease-associated variant, confirming the involvement of DNAH10 in human MMAF"
      explanation: Authors' statement that the mice recapitulate MMAF.
    - reference: PMID:37314648
      reference_title: "Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus"
      explanation: Records the ciliary phenotype behind the limitation.
treatments:
- name: Intracytoplasmic Sperm Injection
  description: >-
    ICSI bypasses the motility and form defect and restores fertilization in
    DNAH10 deficiency. A pooled DNAH2/DNAH6/DNAH10 cohort reported live
    births in five of six couples. Numbers are small.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Intracytoplasmic Sperm Injection
    term:
      id: NCIT:C185482
      label: Intracytoplasmic Sperm Injection
  target_mechanisms:
  - target: Multiple Morphological Abnormalities of the Sperm Flagella
    description: Direct injection makes flagellar propulsion and form irrelevant to fertilization.
    evidence:
    - reference: PMID:42522280
      reference_title: "Genotype-based management of fertilization and cleavage failure: case-series evidence from DNAH10, DNAH12, CFAP47 , and PLCZ1."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "ICSI restored fertilization in DNAH10/DNAH12 deficiency"
      explanation: Human case series showing ICSI success in DNAH10 deficiency.
  evidence:
  - reference: PMID:40592014
    reference_title: "Patients with mutations in DNAH2, DNAH6 and DNAH10 causing multiple morphological abnormalities of human sperm flagella achieve good ICSI outcomes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Moreover, five out of six affected couples achieved a live birth via intracytoplasmic sperm injection (ICSI)."
    explanation: Live births in a cohort pooling DNAH2, DNAH6 and DNAH10 patients.

📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Spermatogenic_Failure_56 · 2026-10-14T20:20:47Z · View source

New entry for MONDO:0030430 (DNAH10-related SPGF56, OMIM 619515), curated from the open stub, which is deleted. Falcon research runs failed with a 503 Edison authentication error (also with dr_fallback='--fallback'), so the report used is research/Spermatogenic_Failure_56-deep-research-claude_code.md from just research-disorder claude_code; preflight-dr returned PASS (DNAH10 mentioned 14 times). Curation rests on PubMed-found papers fetched with just fetch-reference: PMID:34237282, PMID:34657236, PMID:37314648, PMID:41058558 and PMID:40592014 (abstracts), PMID:39996363 and PMID:40898283 (full text), plus the already cached PMID:42522280. The ClinGen record CGGV:assertion_0128b225-6f43-4ed2-b111-a50dde1b25e5-2026-05-07T190000.000Z (Moderate, AR) was generated with just fetch-reference and copied into gene_disease_validity; relationship_type is left unset because CAUSATIVE implies Definitive or Strong. Causal chain: DNAH10 protein loss, co-depletion of DNAH1, DNAH2 and DNAH6, inner dynein arm loss, MMAF, phenotypes; a manchette/intramanchette-transport node (PMID:41058558, MeSH-indexed mouse study) explains the head defect. An EMERGING hypothesis records the conflict between sperm-restricted SPGF56 and DNAH10-related primary ciliary dyskinesia (PMID:37314648 patient and mice). PMID:40373254 (SUN5 plus DNAH10 double homozygote) was read and deliberately not used. Validated with just validate (all snippets verified), count-verified-snippets, validate-terms, check-entity-refs, check-causal-targets, check-duplicate-keys, check-enum-values, check-gene-validity (no conflict) and check-genereviews (NO_CHAPTER).

Claude Code ▸

Research report: Spermatogenic Failure 56 (SPGF56)

claude-haiku-5-5, claude-sonnet-5-5 6 citations 2026-10-14T20:11:00.694293

Research report: Spermatogenic Failure 56 (SPGF56)

Scope and verification. This report rests on a limited set of sources that I read directly. Those are the Tu et al. 2021 full text on PMC (the first ~100,000 of ~114,000 characters; the supplements were not available), the GenCC and LOVD records, and search-result summaries for the other pages. I did not open OMIM, Orphanet, ClinGen, ClinVar, gnomAD or MONDO. Items I could not verify are marked [unverified], and the many sections with no disease-specific data say so. Every CURIE below is a lead and must be looked up before it is bound, per the repository's term contract.

1. Disease information

Overview. SPGF56 is an autosomal recessive male infertility disorder caused by bi-allelic variants in DNAH10 (12q24.31). It presents as asthenoteratozoospermia with multiple morphological abnormalities of the sperm flagella (MMAF) and severely reduced sperm motility (MalaCards; LOVD).
Identifiers.
OMIM:619515 (LOVD).
MedGen C5561978.
MONDO:0030430, as given in the search-result summary. [unverified] My direct search for this ID returned nothing, so confirm it in OLS.
Orphanet, ICD-10/11 and MeSH identifiers were not retrieved.
Synonyms. SPERMATOGENIC FAILURE 56; SPGF56; "DNAH10-related MMAF"; "asthenoteratozoospermia" in the paper title.
Source type. The aggregate disease record (OMIM) is built from patient-level exome data in one report (Tu et al. 2021). No EHR-derived information was found.
Gene-disease validity. GenCC lists a "Moderate" classification (submission SGC-106953.2, evaluated February 2025) (GenCC). A DrugMap/DisGeNET-linked page lists "Limited". Different sources disagree, so copy the tier from the specific source with its own classified_by, and never assign one.
Check ClinGen directly (just check-gene-validity), because I did not read a ClinGen record.

2. Etiology

Cause. Bi-allelic (homozygous or compound heterozygous) DNAH10 variants. No environmental or infectious cause is established.
Genetic risk factors. Tu et al. found five affected men from four unrelated families among 643 Chinese MMAF men, a yield of about 0.78%. Because of the small numbers, no population-level risk estimate exists (PMC8387467).
Modifier genes, protective factors, gene-environment interactions. None reported.

3. Phenotypes

Source: Tu et al. 2021 (PMID:34237282), human clinical. The cohort is five men from four families, so frequencies are qualitative and no per-phenotype percentages exist.

Phenotype	HPO lead (verify)	Notes
Male infertility	HP:0003251	Primary infertility
Asthenozoospermia	HP:0012206	Motility and progressive motility "severely reduced"
Teratozoospermia / MMAF	HP:0012864 (MMAF); HP:0034834 (Abnormal sperm flagellum morphology)	Absent, coiled, short, bent and irregular flagella
Variable sperm concentration	HP:0000798 (Oligospermia), where present	Concentration "varied widely"

Other features. The paper reports no other primary ciliary dyskinesia (PCD) symptoms in these men. Hormone profile and karyotype were not available to me.
Onset and course. Presenting complaint is adult infertility. No progression data exist.
Quality of life. No data.

A separate 2023 report in Frontiers of Medicine describes "DNAH10 deficiency causes primary ciliary dyskinesia in humans and mice" (link). I could not retrieve it. That title is a lead for a respiratory-cilia phenotype, and its authors, PMID and findings are [unverified]. Check it before deciding whether SPGF56 is purely male-limited.

4. Genetic and molecular information

Gene. DNAH10 (dynein axonemal heavy chain 10, encoding an inner dynein arm (IDA) heavy chain). Look up the HGNC ID from cache/hgnc/terms.csv or with runoak, in lowercase hgnc: form.
Variants (Tu et al. 2021, NM_207437.3, from the full text):

Family	Genotype	Origin
T012	Homozygous c.12838G>A (p.Gly4280Arg)	Consanguineous
T089	Homozygous c.7601C>T (p.Thr2534Met)	Consanguineous; parental segregation not checked
H049	Compound heterozygous c.5663G>A (p.Arg1888Gln) and c.11887C>T (p.Arg3963Cys)	Non-consanguineous
NK067 (two brothers)	Compound heterozygous frameshifts c.7260dup (p.Glu2421Argfs26) and c.12235del (p.Ser4079Alafs5)	Non-consanguineous

Classification and frequency. The missense variants were absent from 1000 Genomes and East Asian gnomAD, or very rare overall. SIFT, PolyPhen-2 and MutationTaster predicted them damaging. ClinVar and ACMG classifications were not retrieved. All variants are germline.
Consequence. Loss of function (truncating variants) or presumed hypomorphic function (missense). Patient sperm show absent or markedly reduced DNAH10.
Epigenetic or chromosomal findings. None reported.

5. Environmental information

None reported. There are no environmental, lifestyle or infectious factors, and no ECTO or NCBITaxon terms apply.

6. Mechanism / pathophysiology

Causal chain (steps 1–3 and 5 are shown in the human and mouse data, and step 4 is partly inferred):

Bi-allelic germline DNAH10 variants lead to loss or marked reduction of DNAH10 protein in sperm (shown by immunostaining in patients).
Loss of DNAH10 results in loss of inner dynein arms. TEM showed absent IDAs in about 80% of axonemal cross-sections, with central-pair and doublet disorganization.
IDA loss leads to depletion of the co-assembled IDA components DNAH2 and DNAH6 (almost absent in patient sperm). AKAP4 is mislocalized. DNAH8, DNAH17, DNAI1 and SPAG6 were comparable to controls.
The axoneme then fails to assemble or stay stable during spermiogenesis in elongating spermatids. The authors also speculate about intraflagellar or intramanchette transport roles from STRING predictions, which is not experimentally shown.
Flagellar assembly fails, giving the MMAF morphology: disorganized mitochondrial sheath and outer dense fibers, and absent, short or coiled tails.
The result is severely reduced motility (asthenozoospermia) and male infertility.

Quote supporting the central claim (abstract, PMID:34237282): "DNAH10 encodes an axonemal IDA heavy chain component that is predominantly expressed in the testes" and "DNAH10 is essential for sperm flagellar assembly".

Cell types and processes. Elongated spermatid (CL:0000399 [verify]) and spermatozoon (CL:0000019 [verify]). GO leads include sperm flagellum assembly (GO:0120316 [verify]), axoneme assembly (GO:0035082 [verify]) and inner dynein arm / axonemal dynein complex (GO:0005858 [verify]).
Not available. Metabolic, immune, transcriptomic, proteomic, single-cell, multi-omic and functional-screen data for SPGF56. Expression: abundant in human testis (Human Protein Atlas), and in mouse predominantly testicular, rising from postnatal day 21 and localized to the cytoplasm of elongated spermatids. Mouse trachea and fallopian tube also express it.

7. Anatomical structures affected

Primary. Testis (UBERON:0000473 [verify]), specifically seminiferous tubule germ cells at spermiogenesis, and the sperm flagellum.
Subcellular. Axoneme, with inner dynein arms as the primary lesion, plus the mitochondrial sheath and outer dense fibers disturbed secondarily.
Secondary organs and lateralization. None reported for the human male phenotype, and the condition is bilateral. Whether motile cilia elsewhere are affected is unresolved (see the 2023 report above).

8. Temporal development

Onset. Adult, presenting as infertility (spermatogenesis begins at puberty).
Course. No natural-history, remission or progression data.

9. Inheritance and population

Inheritance. Autosomal recessive (HP:0000007 [verify]).
Consanguinity. Two of the four families were consanguineous (homozygous variants).
Prevalence and incidence. Not available. The only figure is 5/643 (0.78%) of Chinese MMAF men in one cohort, which is a case fraction, not a population frequency.
Population effects. The cohort is Chinese. No founder effect, carrier frequency or sex-ratio data exist (the disease is male-limited by phenotype).
Penetrance, expressivity, anticipation, germline mosaicism. No data.

10. Diagnostics

Semen analysis. Asthenoteratozoospermia with MMAF morphology.
Sperm ultrastructure. H&E and SEM show flagellar defects. TEM shows absent IDAs. Immunofluorescence shows absent or reduced DNAH10, DNAH2 and DNAH6.
Genetic testing. Exome sequencing identified all cases. Include DNAH10 in MMAF or male-infertility gene panels. No dedicated testing guideline was found.
Differential diagnosis. Other MMAF genes (e.g. DNAH1, CFAP family genes). Other genes in the same inner-dynein-arm family can produce overlapping sperm phenotypes.

11. Outcome / prognosis

There are no survival or quality-of-life data. The condition is not life-limiting and is primarily a fertility disorder.
Fertility prognosis. Natural conception is not expected (a knockout mouse is completely infertile). Assisted reproduction can work (see section 12).

12. Treatment

Assisted reproduction (ICSI). In Tu et al., three of five men underwent ICSI and two had good outcomes (Table S7). One partner (H049 II-2) had a poor result: six low-quality oocytes yielded three poor-quality embryos.
NCIT lead: Intracytoplasmic Sperm Injection. Look up the CURIE; I did not retrieve it.
Evidence is anecdotal (n=3), and the pregnancy and live-birth details are not available to me.
No drug, gene therapy or clinical trial is known for SPGF56, and I searched no trial registries.

13. Prevention

No primary prevention exists. Genetic counseling for consanguineous couples, and for the partner's carrier status, is the relevant counseling. Preimplantation or prenatal testing is possible in principle once variants are known, but there is no source for it here.

14. Other species / natural disease

No naturally occurring disease in other species was found (OMIA not searched). The mouse ortholog is Dnah10.

15. Model organisms

Source: Tu et al. 2021 (model organism, in vivo).

Model	Design	Phenotype
Dnah10 knockout mouse	CRISPR-Cas9, exons 2–5 deleted	Males completely infertile. Testis size and weight unchanged. Sperm count reduced, with 100% immotility. Absent, coiled, short or irregular flagella. TEM shows disorganized mitochondrial sheath, outer dense fibers and microtubules. Round spermatids present but no elongated tails at stages VII–VIII.
Dnah10 M/M knock-in	c.13198G>A, equivalent to the patient variant c.12838G>A	Infertile, reduced sperm count, complete immotility, abnormal flagella. TEM shows disorganized axoneme and sheaths, with absent microtubules in the midpiece.

Fidelity. The knockout recapitulates MMAF and infertility. The authors describe it as more severe than the patients' phenotype, which is a limitation. The knock-in models a specific human missense allele.
The 2023 Frontiers of Medicine knock-in and knockout study reported male infertility plus PCD features with flagellar ultrastructure and motility defects (as summarized by search results). I could not read it, so cite it only after verifying.
Resources. MGI/IMPC were not searched, and a Cyagen mouse atlas entry exists for the gene.

Gaps for curation

The OMIM clinical synopsis, ClinGen record, Orphanet entry and ClinVar classifications were not read.
Verify the MONDO ID and all HPO, GO, CL and UBERON leads before binding.
Resolve the "Moderate" (GenCC) versus "Limited" (DrugMap) validity discrepancy against the primary source.
Identify and verify the 2023 PCD-related paper, and check whether any non-sperm phenotype belongs in the entry.

Sources

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Outcome	Count
References checked	2
Resolved	2
Unresolved (possible confabulation)	0
Unverifiable	0
References weighed for topical relevance	2
On topic	2
Off topic	0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome	Count
Terms checked	14
Resolved	12
Unresolved (possible confabulation)	0
Obsolete	1
Unverifiable	1
Terms whose name was checked	3
Terms named correctly	1
Terms named as a different term	1
Terms whose name is worth a second look	1

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

HP:0012206 (1 mention) - the report calls it "Asthenozoospermia"; HP calls it Abnormal sperm motility

Obsolete terms

These terms are real but deprecated. Citing one is not a fabrication; it does mean the report is naming something the ontology has retired:

CL:0000399 (obsolete phloem element) (1 mention)

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

HP:0000798 (1 mention) - the report calls it "Oligospermia"; HP calls it Oligozoospermia, and lists "Oligospermia" among its other names

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: OMIM.

Spermatogenic Failure 56

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Research report: Spermatogenic Failure 56 (SPGF56)

1. Disease information

2. Etiology

3. Phenotypes

4. Genetic and molecular information

5. Environmental information

6. Mechanism / pathophysiology

7. Anatomical structures affected

8. Temporal development

9. Inheritance and population

10. Diagnostics

11. Outcome / prognosis

12. Treatment

13. Prevention

14. Other species / natural disease

15. Model organisms

Gaps for curation

Sources

Reference Validation

Term Validation

Terms the report names something else

Obsolete terms

Terms whose name is worth a second look

Prefixes with no resolver