GDAP2

Chr 1AR

ganglioside induced differentiation associated protein 2

Also known as: MACROD3, SCAR27

NCBI Gene: 54834ENSG00000196505UniProt: Q9NXN4OMIM: 618128

The protein is predicted to function in retinoic acid response pathways and localizes to the lysosomal membrane. Mutations cause spinocerebellar ataxia, autosomal recessive 27, affecting the cerebellum and spinal cord systems. The condition follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM
DNmechanismARLOEUF 0.901 OMIM phenotype
Clinical Summary— GDAP2
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Gene-Disease Validity (ClinGen)
spinocerebellar ataxia, autosomal recessive 27 · ARStrong

Strong evidence — appropriate for clinical testing

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 58 VUS of 107 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.90LOEUF
pLI 0.000
Z-score 2.01
OE 0.61 (0.43–0.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.93Z-score
OE missense 0.84 (0.75–0.94)
219 obs / 261.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.43–0.90)
0≤0.351.4
Missense OE0.84 (0.75–0.94)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 19 / 31.1Missense obs/exp: 219 / 261.2Syn Z: -0.20
DN
0.6260th %ile
GOF
0.5955th %ile
LOF
0.3163th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

107 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic4
VUS58
Likely Benign10
Benign5
14
Pathogenic
4
Likely Pathogenic
58
VUS
10
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
10
0
14
Likely Pathogenic
4
0
0
0
4
VUS
1
55
2
0
58
Likely Benign
0
2
2
6
10
Benign
0
1
1
3
5
Total95815991

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GDAP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Isolated Dystonia as an Initial Presentation of GDAP2-Related Disorder
Di Luca DG et al.·Mov Disord Clin Pract
2023
Autosomal Recessive Cerebellar Ataxia-27 Caused by a Novel Loss-of-Function Variant of Ganglioside-Induced Differentiation Associated Protein 2 in a Spanish Family
Erro ME et al.·Neurol Genet
2025
CRISPR/Cas9-Mediated Knockout of BmGDAP2 in the Silkworm, Bombyx mori: Extended Lifespan and Altered Gene Expression Impacting Developmental Pathways.
Yuan C et al.·Insects
2025
Matching Heterogeneous Cohorts by Projected Principal Components Reveals Two Novel Alzheimer's Disease-Associated Genes in the Hispanic Population
Willett JDS et al.·medRxiv
2025Cohort
Targeting SARS-CoV-2 Nsp3 macrodomain structure with insights from human poly(ADP-ribose) glycohydrolase (PARG) structures with inhibitors
Brosey CA et al.·Prog Biophys Mol Biol
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients