GDAP2
protein-codingganglioside induced differentiation associated protein 2, the group of Macro domain containing|BCH domain containing
Gene summary
Predicted to act upstream of or within response to retinoic acid. Located in lysosomal membrane. Implicated in autosomal recessive spinocerebellar ataxia 27. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~66.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0032706
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0032706
Submitter: ClinGen
*GDAP2* was first reported in relation to autosomal recessive spinocerebellar ataxia in 2018 (Eidhof et al., PMID: 30084953) in which two female patients presented with late onset gait ataxia, speech changes, cognitive impairment, spasticity, and cerebellar atrophy and were found to have biallelic null variants in the GDAP2 gene. Variants in this gene have been reported in at least four probands in three publications (PMIDs: 30084953, 32437512, 32428220). The mechanism of pathogenicity is reported to be loss of function as the probands affected with cerebellar ataxia all have biallelic nonsense or frameshift variants in *GDAP2*. This gene-disease relationship is also supported by an animal model study by Eidhof et al. in which knockdown of the Gdap2 gene in *Drosophila* flies caused abnormal motor behavior, decreased the life span of mutant flies, and increased susceptibility to oxidative stress and starvation (PMID: 30084953). In summary, there is strong evidence to support the relationship between *GDAP2* and autosomal recessive spinocerebellar ataxia. Three years must elapse from the first proposal of the assertion to reach a definitive classification without any valid contradictory evidence. We will re-evaluate this gene-disease relationship at that time to determine if an upgraded classification of definitive is warranted. This classification was approved by the ClinGen Cerebellar Ataxia GCEP on the meeting date December 11, 2024 (SOP Version 11).
Inheritance Pattern: AR
Disease ID:MONDO:0032706
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0032706
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GDAP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017686.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | 3 | 10 | |||
| missense | 56 | 2 | 1 | 59 | ||
| nonsense | 2 | 3 | 1 | 6 | ||
| start loss | 0 | |||||
| frameshift | 2 | 1 | 3 | |||
| splice donor/acceptor (+/-2bp) | 2 | 8 | 10 | |||
| Total | 4 | 6 | 65 | 9 | 4 | 88 |
Highest pathogenic variant AF is 0.00006710784
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060156.1 | 13 | MANE Select | |
| Ensembl | ENSP00000358451.4 | 13 | MANE Select | |
| RefSeq | NP_001129061.1 | 12 | Standard | |
| Ensembl | ENSP00000358450.3 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- response to retinoic acid
Molecular Function
- protein binding
Cellular Component
- lysosomal membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369443
- Coding exons
- 13
- Length
- 66147
- Individuals with no LoFs
- 125678
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 66
- Defined
- 125744
- p
- 0.000262
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.928 | 219 | 261 | 0.838 | 0.0000129 | 3228 |
| Missense (PolyPhen) | 95 | 124.76 | 0.76144 | 1521 | ||
| Synonymous | -0.202 | 97 | 94.5 | 1.03 | 0.00000464 | 952 |
| Loss of Function | 2.01 | 19 | 31.1 | 0.611 | 0.00000186 | 352 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.0023 | 0.0023 | notable |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00025 | 0.00025 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
Intolerance Scores
- LoFtool
- 0.887
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 17.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.212
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |