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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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MDGA1
MAM domain containing glycosylphosphatidylinositol anchor 1
Chromosome 6 · 6p21.2
NCBI Gene: 266727Ensembl: ENSG00000112139.17HGNC: HGNC:19267UniProt: A0A7P0TB62
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GABA-ergic synapseGO:0005615plasma membraneregulation of synaptic membrane adhesioninsomniamajor depressive disorderheart failuremathematical ability
✦AI Summary

MDGA1 (MAM domain containing glycosylphosphatidylinositol anchor 1) is a GPI-anchored cell adhesion molecule critical for cortical development and synaptic organization. During forebrain development, MDGA1 exhibits layer- and area-specific expression patterns in the neocortex, serving as a marker for cortical lamination and patterning 1. The protein functions to aggregate and maintain basal progenitors within the subventricular zone, a process essential for their proliferation and generation of cortical layer neurons 2. MDGA1 contains immunoglobulin and MAM domains that enhance cell-cell adhesion while reducing adhesion to extracellular matrix proteins, increasing cell motility 3. At the synapse, MDGA1 localizes to inhibitory synapses where it may regulate Neuroligin-2 function and influence GABAergic synapse formation 4. Functionally, MDGA1 knockout mice exhibit memory deficits and altered synaptic excitation/inhibition balance 5, though acute deletion does not substantially impair hippocampal synaptic transmission in young mice. Clinically, MDGA1 variants associate with schizophrenia and bipolar disorder risk in Chinese populations 6, while elevated MDGA1 promoter methylation correlates with idiopathic restless legs syndrome, particularly in familial cases 7. Common missense variants showed no association with restless legs syndrome in Caucasian populations 8.

Sources cited
1
MDGA1 is expressed in layer- and area-specific patterns during forebrain development and serves as a unique marker for cortical lamination and area patterning
PMID: 16959869
2
MDGA1 aggregates and maintains basal progenitors within the subventricular zone, essential for their proliferation and cortical layer neuron generation
PMID: 26776515
3
MDGA1 increases cell motility and cell-cell adhesion while reducing adhesion to extracellular matrix proteins through its Ig and MAM domains
PMID: 21505559
4
MDGA1/Mdga2 localizes to inhibitory synaptic clefts and functions as a specificity factor influencing Neuroligin-2 recruitment at inhibitory synapses
PMID: 27565350
5
MDGA1 knockout mice show memory deficits and altered synaptic excitation/inhibition balance, though acute deletion does not impair hippocampal synaptic transmission
PMID: 41530055
6
MDGA1 genetic variants associate with schizophrenia and bipolar disorder risk in Chinese Han population
PMID: 21146959
7
MDGA1 promoter hypermethylation is significantly elevated in idiopathic restless legs syndrome patients and associated with family history
PMID: 40058148
8
Common missense variants in MDGA1 were not associated with idiopathic restless legs syndrome risk in Caucasian Spanish population
PMID: 40724952
Disease Associationsⓘ20
insomniaOpen Targets
0.44Moderate
major depressive disorderOpen Targets
0.43Moderate
heart failureOpen Targets
0.36Weak
mathematical abilityOpen Targets
0.32Weak
infectious meningitisOpen Targets
0.32Weak
ovarian dysfunctionOpen Targets
0.30Weak
intestinal obstructionOpen Targets
0.26Weak
type 1 diabetes mellitusOpen Targets
0.25Weak
acute megakaryoblastic leukaemiaOpen Targets
0.11Weak
mediastinal germ cell tumorOpen Targets
0.11Weak
neuropathyOpen Targets
0.11Weak
depressive disorderOpen Targets
0.06Suggestive
nodular neuronal heterotopiaOpen Targets
0.04Suggestive
Reunion island Larsen syndromeOpen Targets
0.04Suggestive
Reunion Island's Larsen syndromeOpen Targets
0.04Suggestive
autosomal recessive primary microcephalyOpen Targets
0.04Suggestive
Joubert syndromeOpen Targets
0.04Suggestive
Genetic central nervous system malformationOpen Targets
0.04Suggestive
polymicrogyria, bilateral perisylvian, autosomal recessiveOpen Targets
0.03Suggestive
lissencephaly due to LIS1 mutationOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NLGN2Protein interaction99%SOX14Shared pathway40%NAV1Shared pathway33%IL1RAPL2Shared pathway29%DNERShared pathway29%AMIGO3Shared pathway29%
Tissue Expression6 tissues
Brain
100%
Ovary
66%
Lung
18%
Heart
13%
Liver
5%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
MDGA1NLGN2SOX14NAV1IL1RAPL2DNERAMIGO3
PROTEIN STRUCTURE
Preparing viewer…
PDB5V5W · 2.72 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.77LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.61 [0.49–0.77]
RankingsWhere MDGA1 stands among ~20K protein-coding genes
  • #15,622of 20,598
    Most Researched15
  • #6,200of 17,882
    Most Constrained (LOEUF)0.77
Genes detectedMDGA1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Proteomic Analysis of Unbounded Cellular Compartments: Synaptic Clefts.
PMID: 27565350
Cell · 2016
1.00
2
PMID: 40724952
Int J Mol Sci · 2025
0.90
3
The MDGA1 gene confers risk to schizophrenia and bipolar disorder.
PMID: 21146959
Schizophr Res · 2011
0.80
4
Expression of Human MDGA1 Increases Cell Motility and Cell-Cell Adhesion and Reduces Adhesion to Extracellular Matrix Proteins in MDCK Cells.
PMID: 21505559
Cancer Microenviron · 2010
0.70
5
Preliminary findings of DNA hypermethylation of MDGA1 in idiopathic restless legs syndrome.
PMID: 40058148
Sleep Med · 2025
0.60