INSYN2A

Chr 10

inhibitory synaptic factor 2A

Also known as: C10orf141, FAM196A, INSYN2

NCBI Gene: 642938 ENSG00000188916 UniProt: Q6ZSG2 OMIM: 617129

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in inhibitory postsynaptic potential. Predicted to be located in synapse. Predicted to be active in GABA-ergic synapse and postsynaptic density. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.38

Clinical Summary— INSYN2A

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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.

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ClinVar Variants

94 VUS of 103 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.915

Z-score 3.34

OE 0.12 (0.05–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.12Z-score

OE missense 1.02 (0.93–1.12)

308 obs / 302.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.12 (0.05–0.38)

0≤0.351.4

Missense OE?1.02 (0.93–1.12)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 2 / 16.7Missense obs/exp: 308 / 302.1Syn Z: 0.26

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

VUS94

Likely Benign7

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	94	94
Likely Benign	7	7
Benign	0	0
Total	101	101

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

View in ClinVar →

75 pathogenic / likely-pathogenic (of 89) ClinVar copy-number / structural variants overlap INSYN2A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →