INSYN1

Chr 15

inhibitory synaptic factor 1

Also known as: C15orf59

NCBI Gene: 388135 ENSG00000205363 UniProt: Q2T9L4

Predicted to be involved in inhibitory postsynaptic potential. Predicted to be active in postsynaptic density. [provided by Alliance of Genome Resources, Jun 2026]

Research

Predicted to be involved in inhibitory postsynaptic potential. Predicted to be active in postsynaptic density. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.84

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.110

Z-score 1.91

OE 0.32 (0.15–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.83Z-score

OE missense 0.83 (0.73–0.95)

163 obs / 195.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.32 (0.15–0.84)

0≤0.351.4

Missense OE?0.83 (0.73–0.95)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 3 / 9.3Missense obs/exp: 163 / 195.5Syn Z: -0.30

Background carrier burden — how many people carry a rare variant somewhere in INSYN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

360 rare PASS variants

Rare truncating (LoF)

1 in 11,000

20 rare PASS variants

Rare synonymous (reference)

1 in 150

188 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for INSYN1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 240	1 in 8,000
South Asian	~43k	1 in 160	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 180	none seen
European (Finnish)	~27k	1 in 700	≈ 1 in 13,000
Admixed American	~22k	1 in 120	none seen
African / African American	~21k	1 in 160	none seen
East Asian	~20k	1 in 210	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 970	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 320	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓