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GeneE
2 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GRAMD2A
GRAM domain containing 2A
Chromosome 15 · 15q23
NCBI Gene: 196996Ensembl: ENSG00000175318.13HGNC: HGNC:27287UniProt: Q8IUY3
11PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingphosphatidylinositol-4,5-bisphosphate bindingphosphatidylinositol bindingendoplasmic reticulum-plasma membrane tetheringgoutresponse to xenobiotic stimulushypertensionAbnormality of the skeletal system
✦AI Summary

Based on limited published evidence, GRAMD2A is a constitutive tether protein that organizes endoplasmic reticulum-plasma membrane contact sites (EPCS) through phosphatidylinositol lipid-dependent mechanisms. GRAMD2A co-localizes with ESYT2/3 tethers and pre-marks PI(4,5)P2-enriched EPCS destined for store-operated calcium entry, facilitating STIM1 recruitment 1. As a GRAM domain protein, GRAMD2A functionally specializes distinct ER-PM domains and exhibits pleiotropic roles in calcium homeostasis and organelle dynamics 1. GRAMD2A ablation impairs STIM1 translocation at these specialized contact sites 2.

Sources cited
1
GRAMD2A co-localizes with E-Syt2/3 tethers in PIP-dependent manner, pre-marks PI(4,5)P2-enriched ER-PM sites for STIM1, and organizes ER-PM contact sites with roles in calcium homeostasis
PMID: 29469807
2
GRAMD2A pre-marks STIM1-occupied sites and its ablation impairs STIM1 translocation at membrane contact sites
PMID: 29684786
⚠Limited data available — This gene has 2 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
goutOpen Targets
0.11Weak
response to xenobiotic stimulusOpen Targets
0.09Suggestive
hypertensionOpen Targets
0.08Suggestive
Abnormality of the skeletal systemOpen Targets
0.08Suggestive
metabolic syndromeOpen Targets
0.07Suggestive
Abruptio PlacentaeOpen Targets
0.07Suggestive
TinnitusOpen Targets
0.06Suggestive
lung adenocarcinomaOpen Targets
0.06Suggestive
Posterior fusion of lumbosacral vertebrae - blepharoptosisOpen Targets
0.06Suggestive
posterior fusion of lumbosacral vertebrae-blepharoptosis syndromeOpen Targets
0.06Suggestive
type 2 diabetes mellitusOpen Targets
0.05Suggestive
autosomal recessive spondylocostal dysostosisOpen Targets
0.05Suggestive
Klippel-Feil syndrome 3, autosomal dominantOpen Targets
0.04Suggestive
joint contractures, osteochondromas, and B-cell lymphomaOpen Targets
0.04Suggestive
multiple synostoses syndrome 2Open Targets
0.04Suggestive
Testicular regression syndromeOpen Targets
0.03Suggestive
Mayer-Rokitansky-Kuster-Hauser syndromeOpen Targets
0.03Suggestive
Mayer-Rokitansky-Küster-Hauser syndromeOpen Targets
0.03Suggestive
Mayer-Rokitansky-Kuster-Hauser syndrome type 1Open Targets
0.03Suggestive
Microcephaly - cervical spine fusion anomaliesOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SARAFShared pathway50%ESYT3Shared pathway33%ESYT2Shared pathway33%EFHBShared pathway20%ESYT1Shared pathway20%TSPAN18Shared pathway17%
Tissue Expression6 tissues
Lung
100%
Brain
24%
Ovary
6%
Liver
4%
Heart
3%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
GRAMD2ASARAFESYT3ESYT2EFHBESYT1TSPAN18
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8IUY3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.93LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.69 [0.52–0.93]
RankingsWhere GRAMD2A stands among ~20K protein-coding genes
  • #16,776of 20,598
    Most Researched11
  • #8,644of 17,882
    Most Constrained (LOEUF)0.93
Genes detectedGRAMD2A
Sources retrieved2 papers
Response time—
📄 Sources
2
1
GRAM domain proteins specialize functionally distinct ER-PM contact sites in human cells.
PMID: 29469807
Elife · 2018
1.00
2
GRAM marks the spot for STIM. Commentary on "GRAM domain proteins specialize functionally distinct ER-PM contact sites in human cells".
PMID: 29684786
Cell Calcium · 2018
0.50