MDGA2

Chr 14

MAM domain containing glycosylphosphatidylinositol anchor 2

Also known as: MAMDC1, c14_5286

MDGA2 encodes a protein predicted to regulate synapse organization and motor neuron differentiation, with involvement in cell-cell interactions at GABAergic and glutamatergic synapses. Mutations cause neurodevelopmental disorders with intellectual disability and motor dysfunction. The gene shows autosomal recessive inheritance and is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.24
Clinical SummaryMDGA2
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.999
Z-score 5.14
OE 0.10 (0.050.24)
Highly constrained

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

Missense Constraint
1.68Z-score
OE missense 0.76 (0.690.84)
306 obs / 400.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.050.24)
00.351.4
Missense OE0.76 (0.690.84)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 4 / 38.3Missense obs/exp: 306 / 400.4Syn Z: 0.83
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateMDGA2-related developmental and epileptic encephalopathy with abnormal cranial MRILOFAR

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

DN
0.3991th %ile
GOF
0.4678th %ile
LOF
0.66top 25%

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MDGA2 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗