SYT7

Chr 11

synaptotagmin 7

Also known as: IPCA-7, IPCA7, PCANAP7, SYT-VII, SYTVII

NCBI Gene: 9066 ENSG00000011347 UniProt: O43581 OMIM: 604146

The SYT7 protein functions as a calcium sensor that regulates calcium-dependent exocytosis of synaptic vesicles, lysosomal exocytosis for membrane repair, and hormone secretion including insulin and glucagon release. Mutations in this gene cause autosomal recessive congenital myasthenic syndrome, which affects neuromuscular transmission. This gene is highly constrained against loss-of-function variants, indicating that protein function is critical for normal development and cellular processes.

OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate calcium-dependent regulation of membrane trafficking in synaptic transmission. A similar protein in rodents mediates hormone secretion and lysosome exocytosis. In humans, expression of this gene has been associated with prostate cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

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

0.33

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.963

Z-score 3.63

OE 0.10 (0.04–0.33)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.21Z-score

OE missense 0.64 (0.57–0.72)

189 obs / 296.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.33)

0≤0.351.4

Missense OE?0.64 (0.57–0.72)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 2 / 19.1Missense obs/exp: 189 / 296.0Syn Z: 0.17

Background carrier burden — how many people carry a rare variant somewhere in SYT7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 87

734 rare PASS variants

Rare truncating (LoF)

1 in 3,200

71 rare PASS variants

Rare synonymous (reference)

1 in 110

401 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SYT7. 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 100	1 in 4,000
South Asian	~43k	1 in 91	1 in 870
Remaining (unassigned)	~30k	1 in 72	1 in 5,800
European (Finnish)	~27k	1 in 300	1 in 3,800
Admixed American	~22k	1 in 77	1 in 3,700
African / African American	~21k	1 in 61	≈ 1 in 4,800
East Asian	~20k	1 in 94	≈ 1 in 6,200
Ashkenazi Jewish	~13k	1 in 120	1 in 1,500
Middle Eastern	~2,884	1 in 82	≈ 1 in 1,100

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): 12 of 13 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 13.? see exons ↓