GOLGA2-Related Golgin A2 Deficiency

Mendelian Pathograph 4 Show in embeddings browser Neurodevelopmental Disorder Neuromuscular Disease Golgi apparatus disorder

GOLGA2-related Golgin A2 deficiency is a rare autosomal recessive neurodevelopmental and neuromuscular disorder caused by biallelic loss-of-function GOLGA2 variants. GOLGA2 encodes GM130, a cis-Golgi matrix protein required for Golgi apparatus organization, protein secretion and sorting, cell polarity, and microtubule-related cellular functions. Reported affected individuals have developmental delay, seizures, progressive microcephaly, hypotonia, myopathy or muscular dystrophy, elevated creatine kinase, and abnormal corpus callosum or myelination features. Zebrafish knockdown recapitulates small brain size and skeletal-muscle disorganization, supporting GOLGA2 loss as the causal Golgi-organelle defect.

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1
Inheritance
3
Pathophys.
10
Phenotypes
4
Pathograph
1
Genes
1
Deep Research
🏷

Classifications

👪

Inheritance

1
Autosomal recessive inheritance HP:0000007
Reported affected individuals carry homozygous or biallelic loss-of-function GOLGA2 variants in consanguineous families.
Autosomal recessive inheritance
Show evidence (2 references)
PMID:26742501 SUPPORT Human Clinical
"We describe the first human patient with a homozygous apparently loss of function mutation in GOLGA2."
The initial report identified homozygous apparent loss of GOLGA2 function.
PMID:34424553 SUPPORT Human Clinical
"Here we describe a second consanguineous family with the bi-allelic loss of function mutations in GOLGA2."
A second family supports recessive biallelic loss of function as the inheritance mechanism.
⚙

Pathophysiology

3
GOLGA2/GM130 loss disrupts Golgi organization
GOLGA2 loss reduces GM130 function at the cis-Golgi, impairing assembly and organization of the Golgi apparatus as an integrated trafficking and sorting organelle.
GOLGA2 hgnc:4425
Golgi organization GO:0007030 ⚠ ABNORMAL intracellular protein transport GO:0006886 ⚠ ABNORMAL
Golgi apparatus GO:0005794
Downstream
Golgi-dependent trafficking and cell-division dysfunction GM130 loss is expected to impair Golgi-dependent protein sorting, secretion, polarity, and microtubule-related cell-division functions.
Show evidence (2 references)
PMID:26742501 SUPPORT Other
"GOLGA2 encodes GM130, a necessary component for the assembly of GA as a single complex"
The report identifies GM130 as required for Golgi apparatus assembly.
PMID:26742501 SUPPORT Other
"Golgi apparatus (GA) is a membrane-bound organelle that serves a multitude of critical cellular functions including protein secretion and sorting, and cellular polarity."
This supports modeling the primary defect as a Golgi organization and trafficking problem.
Golgi-dependent trafficking and cell-division dysfunction
Disrupted GM130-dependent Golgi organization perturbs protein handling, cell-polarity programs, and microtubule-associated development, affecting tissues with high developmental demand such as brain and skeletal muscle.
vesicle-mediated transport GO:0016192 ⚠ ABNORMAL cell cycle GO:0007049 ⚠ ABNORMAL
Downstream
Brain and skeletal muscle developmental dysfunction
Show evidence (1 reference)
PMID:26742501 SUPPORT Model Organism
"Knockdown of golga2 in zebrafish resulted in severe skeletal muscle disorganization and microcephaly recapitulating loss of function human phenotype."
Zebrafish knockdown supports a causal effect of GOLGA2 loss on muscle and brain development.
Brain and skeletal muscle developmental dysfunction
GOLGA2 loss manifests as impaired brain growth and neurologic development together with skeletal-muscle pathology, including myopathy or muscular dystrophy and elevated creatine kinase.
neuron CL:0000540 skeletal muscle fiber CL:0008002
Show evidence (2 references)
PMID:26742501 SUPPORT Human Clinical
"The phenotype is a neuromuscular disorder characterized by developmental delay, seizures, progressive microcephaly, and muscular dystrophy."
The initial report defines the neurologic and muscular phenotype.
PMID:34424553 SUPPORT Human Clinical
"The patient exhibits microcephaly, seizures, and myopathy similar to the previously reported patient with GOLGA2 mutation."
The second family confirms overlapping brain and muscle involvement.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for GOLGA2-Related Golgin A2 Deficiency Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

10
Eye 1
Strabismus Strabismus HP:0000486
Show evidence (1 reference)
PMID:26742501 SUPPORT Human Clinical
"around which time she was diagnosed with strabismus."
The full-text case report explicitly documents strabismus.
Metabolism 1
Elevated circulating creatine kinase concentration Elevated circulating creatine kinase concentration HP:0003236
Show evidence (1 reference)
PMID:26742501 SUPPORT Human Clinical
"Creatine Kinase (CK) was persistently elevated with a range of 959-1,368U/L."
The full-text case description supports elevated CK as a laboratory feature of the myopathy.
Musculoskeletal 3
Hypotonia Hypotonia HP:0001252
Show evidence (1 reference)
PMID:26742501 SUPPORT Human Clinical
"She also had central hypotonia."
The full-text case report explicitly documents central hypotonia.
Myopathy Myopathy HP:0003198
Show evidence (1 reference)
PMID:34424553 SUPPORT Human Clinical
"microcephaly, seizures, and myopathy"
The second family report explicitly lists myopathy.
Muscular dystrophy Muscular dystrophy HP:0003560
Show evidence (1 reference)
PMID:26742501 SUPPORT Human Clinical
"progressive microcephaly, and muscular dystrophy."
The abstract explicitly reports muscular dystrophy.
Nervous System 2
Global developmental delay Global developmental delay HP:0001263
Show evidence (1 reference)
PMID:26742501 SUPPORT Human Clinical
"The phenotype is a neuromuscular disorder characterized by developmental delay"
The initial report explicitly lists developmental delay.
Seizures Seizure HP:0001250
Show evidence (1 reference)
PMID:34424553 SUPPORT Human Clinical
"The patient exhibits microcephaly, seizures, and myopathy"
The second family report explicitly lists seizures.
Growth 1
Failure to thrive Failure to thrive HP:0001508
Show evidence (1 reference)
PMID:26742501 SUPPORT Human Clinical
"Microcephaly, hypotonia and failure to thrive were noticeable starting at 4m of age"
The full-text case report explicitly documents failure to thrive.
Other 2
Progressive microcephaly Progressive microcephaly HP:0000253
Show evidence (1 reference)
PMID:26742501 SUPPORT Human Clinical
"developmental delay, seizures, progressive microcephaly"
The initial case explicitly includes progressive microcephaly.
Thin corpus callosum Thin corpus callosum HP:0033725
Show evidence (1 reference)
PMID:26742501 SUPPORT Human Clinical
"Brain MRI revealed nonspecific cerebral volume loss with delayed myelination and thinning of corpus callosum."
The full-text MRI description supports thin corpus callosum.
🧬

Genetic Associations

1
GOLGA2 biallelic loss-of-function variants (Loss of function mutation)
Gene: GOLGA2 hgnc:4425 relationship_type: CAUSATIVE
Autosomal recessive inheritance
Show evidence (2 references)
PMID:26742501 SUPPORT Human Clinical
"the homozygous truncating candidate in GOLGA2 was an attractive candidate in view of its established role as a master regulator of GA"
Exome/autozygome analysis identified homozygous truncating GOLGA2 as the causal candidate in the first patient.
PMID:34424553 SUPPORT Human Clinical
"Recessive loss of function mutation in GOLGA2 has been previously reported in a single family with muscular dystrophy and microcephaly."
The second-family report summarizes the previous recessive loss-of-function association.
{ }

Source YAML

click to show 
name: GOLGA2-Related Golgin A2 Deficiency
creation_date: "2026-07-06T12:00:00Z"
category: Mendelian
description: >-
  GOLGA2-related Golgin A2 deficiency is a rare autosomal recessive
  neurodevelopmental and neuromuscular disorder caused by biallelic
  loss-of-function GOLGA2 variants. GOLGA2 encodes GM130, a cis-Golgi matrix protein
  required for Golgi apparatus organization, protein secretion and sorting, cell
  polarity, and microtubule-related cellular functions. Reported affected
  individuals have developmental delay, seizures, progressive microcephaly,
  hypotonia, myopathy or muscular dystrophy, elevated creatine kinase, and
  abnormal corpus callosum or myelination features. Zebrafish knockdown
  recapitulates small brain size and skeletal-muscle disorganization, supporting
  GOLGA2 loss as the causal Golgi-organelle defect.
parents:
- Neurodevelopmental Disorder
- Neuromuscular Disease
- Golgi apparatus disorder
synonyms:
- GOLGA2 deficiency
- Golgin A2 deficiency
- GM130 deficiency
- GOLGA2-related neuromuscular disorder
notes: >-
  WP-068 seed OMIM:620240 is retained as an external assertion. No exact local
  MONDO class was found for GOLGA2-related Golgin A2 deficiency, so disease_term
  is intentionally omitted pending ontology coverage.
external_assertions:
- name: OMIM GOLGA2-related Golgin A2 deficiency record
  source: OMIM
  assertion_type: disease_record
  external_id: OMIM:620240
  description: OMIM phenotype identifier supplied by WP-068 for GOLGA2-related Golgin A2 deficiency.
classifications:
  icimd_category:
  - classification_value: vesicular_trafficking
    notes: >-
      WP-068 classification 19.6.71.01: Complex Molecule and Organelle
      Metabolism, disorders of organelle biogenesis, dynamics and interactions,
      disorders of vesicular trafficking.
inheritance:
- name: Autosomal recessive inheritance
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    Reported affected individuals carry homozygous or biallelic loss-of-function
    GOLGA2 variants in consanguineous families.
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We describe the first human patient with a homozygous apparently loss of
      function mutation in GOLGA2.
    explanation: >-
      The initial report identified homozygous apparent loss of GOLGA2 function.
  - reference: PMID:34424553
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Here we describe a second consanguineous family with the bi-allelic loss
      of function mutations in GOLGA2.
    explanation: >-
      A second family supports recessive biallelic loss of function as the
      inheritance mechanism.
pathophysiology:
- name: GOLGA2/GM130 loss disrupts Golgi organization
  description: >-
    GOLGA2 loss reduces GM130 function at the cis-Golgi, impairing assembly and
    organization of the Golgi apparatus as an integrated trafficking and sorting
    organelle.
  genes:
  - preferred_term: GOLGA2
    term:
      id: hgnc:4425
      label: GOLGA2
  biological_processes:
  - preferred_term: Golgi organization
    modifier: ABNORMAL
    term:
      id: GO:0007030
      label: Golgi organization
  - preferred_term: intracellular protein transport
    modifier: ABNORMAL
    term:
      id: GO:0006886
      label: intracellular protein transport
  locations:
  - preferred_term: Golgi apparatus
    term:
      id: GO:0005794
      label: Golgi apparatus
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      GOLGA2 encodes GM130, a necessary component for the assembly of GA as a
      single complex
    explanation: >-
      The report identifies GM130 as required for Golgi apparatus assembly.
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Golgi apparatus (GA) is a membrane-bound organelle that serves a multitude
      of critical cellular functions including protein secretion and sorting,
      and cellular polarity.
    explanation: >-
      This supports modeling the primary defect as a Golgi organization and
      trafficking problem.
  downstream:
  - target: Golgi-dependent trafficking and cell-division dysfunction
    causal_link_type: DIRECT
    description: >-
      GM130 loss is expected to impair Golgi-dependent protein sorting,
      secretion, polarity, and microtubule-related cell-division functions.
    evidence:
    - reference: PMID:26742501
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        GA functions as a microtubule organizing center that nucleates
        microtubules
      explanation: >-
        The source supports GM130/Golgi involvement in microtubule-related
        cellular organization.
- name: Golgi-dependent trafficking and cell-division dysfunction
  description: >-
    Disrupted GM130-dependent Golgi organization perturbs protein handling,
    cell-polarity programs, and microtubule-associated development, affecting
    tissues with high developmental demand such as brain and skeletal muscle.
  biological_processes:
  - preferred_term: vesicle-mediated transport
    modifier: ABNORMAL
    term:
      id: GO:0016192
      label: vesicle-mediated transport
  - preferred_term: cell cycle
    modifier: ABNORMAL
    term:
      id: GO:0007049
      label: cell cycle
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Knockdown of golga2 in zebrafish resulted in severe skeletal muscle
      disorganization and microcephaly recapitulating loss of function human
      phenotype.
    explanation: >-
      Zebrafish knockdown supports a causal effect of GOLGA2 loss on muscle and
      brain development.
  downstream:
  - target: Brain and skeletal muscle developmental dysfunction
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - disrupted Golgi apparatus organization
    - impaired protein secretion and sorting
    - altered microtubule-dependent cell behavior
    evidence:
    - reference: PMID:26742501
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The phenotype is a neuromuscular disorder characterized by developmental
        delay, seizures, progressive microcephaly, and muscular dystrophy.
      explanation: >-
        The original human case supports the brain and skeletal-muscle clinical
        consequences.
- name: Brain and skeletal muscle developmental dysfunction
  description: >-
    GOLGA2 loss manifests as impaired brain growth and neurologic development
    together with skeletal-muscle pathology, including myopathy or muscular
    dystrophy and elevated creatine kinase.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  - preferred_term: skeletal muscle fiber
    term:
      id: CL:0008002
      label: skeletal muscle fiber
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The phenotype is a neuromuscular disorder characterized by developmental
      delay, seizures, progressive microcephaly, and muscular dystrophy.
    explanation: >-
      The initial report defines the neurologic and muscular phenotype.
  - reference: PMID:34424553
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The patient exhibits microcephaly, seizures, and myopathy similar to the
      previously reported patient with GOLGA2 mutation.
    explanation: >-
      The second family confirms overlapping brain and muscle involvement.
phenotypes:
- category: Neurological
  name: Progressive microcephaly
  phenotype_term:
    preferred_term: Progressive microcephaly
    term:
      id: HP:0000253
      label: Progressive microcephaly
  description: >-
    Progressive microcephaly was reported in the initial GOLGA2-deficient
    patient.
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "developmental delay, seizures, progressive microcephaly"
    explanation: >-
      The initial case explicitly includes progressive microcephaly.
- category: Neurological
  name: Global developmental delay
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  description: >-
    Developmental delay is part of the reported neurologic phenotype.
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The phenotype is a neuromuscular disorder characterized by developmental
      delay
    explanation: >-
      The initial report explicitly lists developmental delay.
- category: Neurological
  name: Seizures
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  description: >-
    Seizures were present in both reported families.
  evidence:
  - reference: PMID:34424553
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient exhibits microcephaly, seizures, and myopathy"
    explanation: >-
      The second family report explicitly lists seizures.
- category: Neurological
  name: Hypotonia
  phenotype_term:
    preferred_term: Hypotonia
    term:
      id: HP:0001252
      label: Hypotonia
  description: >-
    Central hypotonia was reported in the first GOLGA2-deficient individual.
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "She also had central hypotonia."
    explanation: >-
      The full-text case report explicitly documents central hypotonia.
- category: Ophthalmologic
  name: Strabismus
  phenotype_term:
    preferred_term: Strabismus
    term:
      id: HP:0000486
      label: Strabismus
  description: >-
    Strabismus was reported in the first GOLGA2-deficient individual.
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "around which time she was diagnosed with strabismus."
    explanation: >-
      The full-text case report explicitly documents strabismus.
- category: Neurological
  name: Thin corpus callosum
  phenotype_term:
    preferred_term: Thin corpus callosum
    term:
      id: HP:0033725
      label: Thin corpus callosum
  description: >-
    Thinning of the corpus callosum was seen on brain MRI.
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Brain MRI revealed nonspecific cerebral volume loss with delayed myelination and thinning of corpus callosum."
    explanation: >-
      The full-text MRI description supports thin corpus callosum.
- category: Growth
  name: Failure to thrive
  phenotype_term:
    preferred_term: Failure to thrive
    term:
      id: HP:0001508
      label: Failure to thrive
  description: >-
    Failure to thrive was reported in the first GOLGA2-deficient individual.
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Microcephaly, hypotonia and failure to thrive were noticeable starting at 4m of age"
    explanation: >-
      The full-text case report explicitly documents failure to thrive.
- category: Muscular
  name: Myopathy
  phenotype_term:
    preferred_term: Myopathy
    term:
      id: HP:0003198
      label: Myopathy
  description: >-
    Myopathy or muscular dystrophy is a recurring feature.
  evidence:
  - reference: PMID:34424553
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "microcephaly, seizures, and myopathy"
    explanation: >-
      The second family report explicitly lists myopathy.
- category: Muscular
  name: Muscular dystrophy
  phenotype_term:
    preferred_term: Muscular dystrophy
    term:
      id: HP:0003560
      label: Muscular dystrophy
  description: >-
    The initial case was described as having muscular dystrophy.
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "progressive microcephaly, and muscular dystrophy."
    explanation: >-
      The abstract explicitly reports muscular dystrophy.
- category: Laboratory
  name: Elevated circulating creatine kinase concentration
  phenotype_term:
    preferred_term: Elevated circulating creatine kinase concentration
    term:
      id: HP:0003236
      label: Elevated circulating creatine kinase concentration
  description: >-
    Persistently elevated creatine kinase was reported in the initial patient.
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Creatine Kinase (CK) was persistently elevated with a range of 959-1,368U/L."
    explanation: >-
      The full-text case description supports elevated CK as a laboratory
      feature of the myopathy.
genetic:
- name: GOLGA2 biallelic loss-of-function variants
  association: Loss of function mutation
  relationship_type: CAUSATIVE
  presence: Pathogenic
  gene_term:
    preferred_term: GOLGA2
    term:
      id: hgnc:4425
      label: GOLGA2
  inheritance:
  - name: Autosomal recessive inheritance
    inheritance_term:
      preferred_term: Autosomal recessive inheritance
      term:
        id: HP:0000007
        label: Autosomal recessive inheritance
  features: >-
    Reported pathogenic variants are biallelic loss-of-function alleles,
    including a homozygous frameshift in the first report and biallelic loss of
    function in a second consanguineous family.
  evidence:
  - reference: PMID:26742501
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the homozygous truncating candidate in GOLGA2 was an attractive candidate
      in view of its established role as a master regulator of GA
    explanation: >-
      Exome/autozygome analysis identified homozygous truncating GOLGA2 as the
      causal candidate in the first patient.
  - reference: PMID:34424553
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Recessive loss of function mutation in GOLGA2 has been previously reported
      in a single family with muscular dystrophy and microcephaly.
    explanation: >-
      The second-family report summarizes the previous recessive
      loss-of-function association.
📚

References & Deep Research

Deep Research

1
GOLGA2-Related Golgin A2 Deficiency Deep Research Fallback ▸

GOLGA2-Related Golgin A2 Deficiency Deep Research Fallback

Scope

No provider-generated deep research artifact was present on the WP-068 branch. This fallback audit documents the literature scope used to curate and review the GOLGA2-related entry from cached PubMed references.

Evidence Scope Used For Curation

  • PMID:26742501 for the first human biallelic GOLGA2 loss-of-function case, GM130/Golgi apparatus biology, developmental delay, seizures, progressive microcephaly, muscular dystrophy, elevated creatine kinase, hypotonia, strabismus, failure to thrive, thin corpus callosum, mild liver enzyme elevation, and zebrafish knockdown evidence for microcephaly and skeletal muscle disorganization.
  • PMID:34424553 for the second consanguineous family with biallelic GOLGA2 loss of function and overlapping microcephaly, seizures, and myopathy.

Curation Conclusions

The supported model is biallelic GOLGA2/GM130 loss impairing cis-Golgi organization, intracellular protein transport, secretion/sorting, and microtubule-related developmental functions. Human and zebrafish evidence support a neurodevelopmental and neuromuscular phenotype with microcephaly, seizures, developmental delay, hypotonia, strabismus, thin corpus callosum, failure to thrive, myopathy or muscular dystrophy, and elevated creatine kinase.