SNAP23

Chr 15

synaptosome associated protein 23

Also known as: HsT17016, SNAP-23, SNAP23A, SNAP23B

NCBI Gene: 8773 ENSG00000092531 UniProt: O00161 OMIM: 602534

Specificity of vesicular transport is regulated, in part, by the interaction of a vesicle-associated membrane protein termed synaptobrevin/VAMP with a target compartment membrane protein termed syntaxin. These proteins, together with SNAP25 (synaptosome-associated protein of 25 kDa), form a complex which serves as a binding site for the general membrane fusion machinery. Synaptobrevin/VAMP and syntaxin are believed to be involved in vesicular transport in most, if not all cells, while SNAP25 is present almost exclusively in the brain, suggesting that a ubiquitously expressed homolog of SNAP25 exists to facilitate transport vesicle/target membrane fusion in other tissues. The protein encoded by this gene is structurally and functionally similar to SNAP25 and binds tightly to multiple syntaxins and synaptobrevins/VAMPs. It is an essential component of the high affinity receptor for the general membrane fusion machinery and is an important regulator of transport vesicle docking and fusion. Two alternative transcript variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM 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

0.38

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.924

Z-score 3.03

OE 0.08 (0.03–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.83Z-score

OE missense 0.78 (0.66–0.93)

88 obs / 113.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.38)

0≤0.351.4

Missense OE?0.78 (0.66–0.93)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 1 / 12.6Missense obs/exp: 88 / 113.0Syn Z: 0.96

Background carrier burden — how many people carry a rare variant somewhere in SNAP23?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

346 rare PASS variants

Rare truncating (LoF)

1 in 1,500

55 rare PASS variants

Rare synonymous (reference)

1 in 1,200

72 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SNAP23. 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 290	1 in 5,100
South Asian	~43k	1 in 170	1 in 660
Remaining (unassigned)	~30k	1 in 210	1 in 4,300
European (Finnish)	~27k	1 in 1,300	1 in 610
Admixed American	~22k	1 in 250	≈ 1 in 7,300
African / African American	~21k	1 in 140	1 in 1,800
East Asian	~20k	1 in 350	1 in 2,400
Ashkenazi Jewish	~13k	1 in 310	none seen
Middle Eastern	~2,884	1 in 140	≈ 1 in 1,400

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): 5 of 7 coding exons well covered in gnomAD exomes; exons 2, 8 marginal. Genomes: all 7.? see exons ↓