Fetching the two key CFAP58 papers into the reference cache so I can quote their abstracts exactly.

Research Report: Spermatogenic Failure 49 (SPGF49; MONDO:0030868)

Limits of this report. I could not read the full text of any primary paper. PMC and PubMed returned CAPTCHA and cookie pages. A just fetch-reference call also needed approval that was not granted, so nothing was added to references_cache/.

• Bibliographic details and findings below come from search snippets and Europe PMC record summaries. They are not exact abstract quotes.
• Paraphrases need replacing with verified snippets (just fetch-reference PMID:…, then just count-verified-snippets) before they go into any evidence block.
• No ontology CURIEs other than the MONDO ID are given. The repo rules forbid writing CURIEs from memory, so each suggested term below is a name to look up.
• kb/disorders/Spermatogenic_Failure_49.yaml already exists as an 8-line skeleton: name, category and disease_term only. stubs/Spermatogenic_Failure_49.yaml is still present and should be deleted by the curation PR.

1. Disease information

SPGF49 is an autosomal recessive form of male infertility. It is caused by biallelic loss-of-function variants in CFAP58, and sperm show multiple morphological abnormalities of the flagella (MMAF), a severe asthenoteratozoospermia.

• Identifiers: MONDO:0030868 (from the stub); OMIM #619144 (LOVD disease record).
• Synonyms: SPGF49. SPGF98 appears as a synonym in Disease Ontology (DOID:0112271, Glycosmos). The MMAF label is a phenotype descriptor, not a separate disease name.
• Source level: aggregated, from case series and cohorts. No EHR-derived data were found.
• Not located: Orphanet, ICD-10/11 and MeSH mappings. These need a direct check.

2. Etiology

• Causal factor: genetic. CFAP58 (10q25.1) is the only gene associated with this OMIM entry (LOVD).
• Discovery: He et al. 2020, AJHG, PMID:32791035. Whole-exome sequencing of 90 Chinese MMAF men found biallelic loss-of-function CFAP58 variants in 5 unrelated men (5.6%).
• Replication: Sha et al. 2021, Clin Genet 99(3):443–448, PMID:33314088. Biallelic CFAP58 variants were found in 2 of 55 MMAF men, and CFAP58 protein was absent from their sperm.
• Modifier genes, protective factors, gene–environment interactions: none reported in what I found.

3. Phenotypes

• Frequency: all five He 2020 probands were reported to have typical MMAF, so the penetrance of the sperm phenotype is effectively complete in affected males.
• Not retrieved: per-patient percentages of each flagellar morphology, semen parameters, and variant-level details (cDNA and protein changes).
• Onset and progression: not described. Infertility is detected in adulthood on presentation.
• Syndromic features: I found none reported. Cilia-related disease, such as primary ciliary dyskinesia or situs abnormalities, is not described in these cohorts, but I did not confirm absence from full text.
• Quality of life: not reported.

4. Genetic and molecular information

• Gene: CFAP58 (cilia- and flagella-associated protein 58), 10q25.1. Look up the HGNC ID in the lowercase hgnc: form and check it with just validate-terms.
• Variants: loss-of-function alleles, shown in the human cohorts as bi-allelic (homozygous or compound heterozygous) variants. Specific variants were not retrieved. Pull them from the full text of PMID:32791035 and PMID:33314088, and from ClinVar.
• Functional consequence: loss of function. Sperm from affected men lack or have reduced CFAP58 protein (Sha 2021).
• Not retrieved: population allele frequencies and ClinGen gene–disease validity tier. Run just list-gene-validity and check ClinGen for a CGGV record before adding any tier.
• Epigenetic and chromosomal abnormalities: none known.

5. Environmental information

No environmental, lifestyle or infectious contributors are reported. Leave the environmental: section absent.

6. Mechanism and pathophysiology

Causal chain:

1. Biallelic loss-of-function variants in CFAP58 reduce or abolish CFAP58 protein in the germline. This is demonstrated in patient sperm, which lack the protein (Sha 2021).
2. CFAP58 is a testis-enriched protein that localizes along the flagellum and concentrates in the midpiece. Without it, the axoneme and mitochondrial sheath assemble abnormally during spermiogenesis.
3. Sperm from affected men show lower levels of the axonemal markers SPAG6 and SPEF2 and of the mitochondrial sheath protein HSP60. TEM shows axonemal and mitochondrial sheath malformations (He 2020).
4. Flagella are short, coiled, bent or absent, so sperm have little or no progressive motility.
5. The result is asthenoteratozoospermia and male infertility.

Branches and inferred steps:

• Manchette and head shaping. A later review reports that knockout mice also have abnormal sperm head shaping linked to manchette impairment, plus increased sperm apoptosis. I did not see this in the original papers, so check it before curating.
• Interactors. Cfap58 is reported to interact with IFT88 and CCDC42. This comes from a review, so verify it in primary papers.
• Centriole link (in vitro only). In cultured cells, Cfap58 localizes like the mother-centriole protein Odf2/Cenexin. It is needed for primary cilium elongation and is linked to Notch signaling (PMC6970087). Whether this operates in human spermatogenesis is inferred, not shown.
• Suggested terms to look up: GO sperm flagellum assembly, axoneme assembly and mitochondrial sheath organization; GO cellular components sperm flagellum, axoneme and sperm midpiece; CL terms for spermatid and spermatozoon.
• Not found: transcriptomic, proteomic or single-cell studies in patients.

7. Anatomical structures affected

• Organ and tissue: testis (seminiferous epithelium) and male reproductive tract; the germ-cell lineage, in particular elongating spermatids.
• Subcellular: sperm flagellum, axoneme, mitochondrial sheath and midpiece.
• Lateralization: not applicable.

8. Temporal development

Onset is not defined beyond adult presentation with infertility. No progression, remission or critical-period data were found.

9. Inheritance and population

• Inheritance: autosomal recessive (OMIM #619144).
• Population: the two published cohorts are both Chinese. Prevalence is unknown. Frequencies of 5.6% (5/90) and about 3.6% (2/55) of MMAF cohorts are cohort-specific rates, not population prevalence.
• Sex ratio: affected males only. Female carriers are not reported to be affected.
• Not retrieved: founder variants, carrier frequency and consanguinity details.

10. Diagnostics

• Semen analysis shows asthenoteratozoospermia with an MMAF morphology.
• Sperm TEM shows axonemal and mitochondrial sheath defects.
• Immunofluorescence or western blot can show reduced CFAP58, SPAG6, SPEF2 and HSP60 in sperm.
• Genetic testing: whole-exome sequencing was how both cohorts found the gene. In practice a male-infertility or MMAF gene panel including CFAP58 would be used.
• Differential diagnosis: other MMAF genes, such as DNAH1, CFAP43, CFAP44, FSIP2 and SPEF2. Primary ciliary dyskinesia should be excluded on clinical grounds.
• Not retrieved: LOINC codes. Look these up with the repo's LOINC workflow if you add semen-analysis measurements.

11. Outcome and prognosis

Not studied beyond fertility. No survival or morbidity data were found. Prognosis for natural conception is poor, and assisted reproduction is the relevant outcome (see section 12).

12. Treatment

• No disease-specific drug or gene therapy was found.
• Assisted reproduction: Sha 2021 reports that one couple had a successful outcome with ICSI, and its authors conclude that ICSI is an effective treatment. With one couple, this cannot be generalized.
• Related context: an MMAF cohort of 38 men with other causal genes had lower fertilization, blastocyst formation and cumulative pregnancy rates after ICSI than an oligoasthenospermia comparison group, with no difference in neonatal outcomes (Front Endocrinol 2024). It did not include CFAP58 cases, so do not attribute it to this disease.
• Clinical trials: none searched. Check ClinicalTrials.gov before adding any.
• Suggested NCIT terms to look up: an in vitro fertilization or intracytoplasmic sperm injection procedure, and genetic counseling.

13. Prevention

• Genetic counseling is relevant because the condition is recessive.
• Preimplantation genetic testing is theoretically applicable. I found no source specific to CFAP58.
• No other prevention measures apply.

14. Other species and natural disease

I did not search OMIA, so I cannot say whether a natural animal disease is known. Leave this section absent unless a search finds one.

15. Model organisms

• Mouse Cfap58 knockout (CRISPR/Cas9), He 2020: infertile males with severe flagellar defects (short, bent and similar), matching the MMAF sperm phenotype. This is MODEL_ORGANISM evidence and supports the loss-of-function mechanism with good fidelity for the sperm phenotype.
• Cultured cells: Cfap58 and Odf2 localization, and the primary cilium and Notch link (PMC6970087). This is IN_VITRO evidence.
• Not checked: MGI/IMPC records and zebrafish or other models.

Curation notes for the entry

• The only primary clinical citations found are PMID:32791035 and PMID:33314088. Fetch them with just fetch-reference, then copy exact snippets and variant details from the cached text.
• Classify evidence sources as HUMAN_CLINICAL for the cohorts and MODEL_ORGANISM for the knockout mouse, splitting items where a paper mixes the two.
• An earlier search surfaced a related paper on a different gene, CFAP251 (Frontiers in Genetics 2021, DOI 10.3389/fgene.2021.783790). Do not cite it for CFAP58.

Sources: - LOVD disease record, SPGF49 (OMIM:619144) - He et al. 2020, AJHG (PMC7477015) - Sha et al. 2021, Clin Genet - Cfap58/Odf2 cell study (PMC6970087) - Glycosmos DOID:0112271 - Frontiers in Endocrinology 2024, MMAF ICSI cohort - Frontiers in Genetics 2021, CFAP251 case

Reference Validation

Checked with linkml-reference-validator 0.3.0.

All extracted references resolved successfully.

Term Validation

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

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.

2 of 3 terms resolved to a current term; the rest could not be looked up either way.