GM2A

Chr 5AR

ganglioside GM2 activator

Also known as: GM2-AP, GM2AP, SAP-3

This gene encodes a glycolipid transport protein that acts as a cofactor for lysosomal beta-hexosaminidase A, extracting GM2 ganglioside molecules from membranes and presenting them for degradation. Mutations cause GM2-gangliosidosis AB variant (also called AB variant of Tay-Sachs disease), an autosomal recessive lysosomal storage disorder affecting the nervous system. The gene is not highly constrained against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.281 OMIM phenotype
Clinical SummaryGM2A
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Gene-Disease Validity (ClinGen)
Tay-Sachs disease AB variant · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.28LOEUF
pLI 0.031
Z-score 1.14
OE 0.50 (0.231.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.30Z-score
OE missense 1.08 (0.931.26)
116 obs / 107.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.50 (0.231.28)
00.351.4
Missense OE1.08 (0.931.26)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 3 / 6.0Missense obs/exp: 116 / 107.3Syn Z: -1.10
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGM2A-related GM2-gangliosidosis, type ABLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6840th %ile
GOF
0.4678th %ile
LOF
0.2580th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GM2A · 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

No active trials found for this gene.

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Clinical Literature
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