INSYN2A

Chr 10

inhibitory synaptic factor 2A

Also known as: C10orf141, FAM196A, INSYN2

The protein functions as a scaffold component at inhibitory synapses, which dampen neuronal activity through postsynaptic hyperpolarization and are essential for precise neural signaling in the central nervous system. Mutations in this gene cause neurodevelopmental disorders with epilepsy, and inheritance follows an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to cause significant clinical effects.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.38
Clinical SummaryINSYN2A
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
74 unique Pathogenic / Likely Pathogenic· 107 VUS of 190 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.38LOEUF
pLI 0.915
Z-score 3.34
OE 0.12 (0.050.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.12Z-score
OE missense 1.02 (0.931.12)
308 obs / 302.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.12 (0.050.38)
00.351.4
Missense OE1.02 (0.931.12)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 2 / 16.7Missense obs/exp: 308 / 302.1Syn Z: 0.26

ClinVar Variant Classifications

190 submitted variants in ClinVar

Classification Summary

Pathogenic73
Likely Pathogenic1
VUS107
Likely Benign7
73
Pathogenic
1
Likely Pathogenic
107
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
73
0
73
Likely Pathogenic
0
0
1
0
1
VUS
0
94
13
0
107
Likely Benign
0
7
0
0
7
Benign
0
0
0
0
0
Total0101870188

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

View in ClinVar →

Protein Context — Lollipop Plot

INSYN2A · 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 →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found