MDGA2

Chr 14

MAM domain containing glycosylphosphatidylinositol anchor 2

Also known as: MAMDC1, c14_5286

NCBI Gene: 161357ENSG00000139915UniProt: Q7Z553

Predicted to be involved in regulation of synapse organization and spinal cord motor neuron differentiation. Predicted to act upstream of or within several processes, including motor behavior; negative regulation of neuron apoptotic process; and neuron migration. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in GABA-ergic synapse; glutamatergic synapse; and postsynaptic density membrane. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
11
Pathogenic / LP
69
ClinVar variants
7
Pubs (1 yr)
1.7
Missense Z
0.24
LOEUF· LoF intolerant
Clinical Summary— MDGA2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 53 VUS of 69 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.999
Z-score 5.14
OE 0.10 (0.05–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.68Z-score
OE missense 0.76 (0.69–0.84)
306 obs / 400.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.05–0.24)
0≤0.351.4
Missense OE0.76 (0.69–0.84)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 4 / 38.3Missense obs/exp: 306 / 400.4Syn Z: 0.83
LOF
DN
0.3991th %ile
GOF
0.4678th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic2
VUS53
Likely Benign2
Benign3
9
Pathogenic
2
Likely Pathogenic
53
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
1
0
1
0
2
VUS
1
31
19
2
53
Likely Benign
0
1
0
1
2
Benign
0
2
0
1
3
Total23429469

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

View in ClinVar →

MDGA2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MDGA2-related developmental and epileptic encephalopathy with abnormal cranial MRI

moderate
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantframeshift variantstop gainedwhole partial gene deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
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