SYT12

Chr 11

synaptotagmin 12

Also known as: sytXII

NCBI Gene: 91683 ENSG00000173227 UniProt: Q8IV01

The protein encoded by this gene is a synaptic vesicle phosphoprotein that enhances spontaneous neurotransmitter release and is essential for mossy-fiber long-term potentiation in the hippocampus, unlike other synaptotagmins as it does not bind calcium or phospholipids. Pathogenic variants in SYT12 cause autosomal recessive intellectual disability with seizures and language delay. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

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. Studies of the orthologous gene in rat have shown that the encoded protein selectively modulates spontaneous synaptic-vesicle exocytosis and may also be involved in regulating calcium independent secretion in nonneuronal cells. Alternative splicing results in multiple transcript variants. The gene has previously been referred to as synaptotagmin XI but has been renamed synaptotagmin XII to be standard with mouse and rat official nomenclature.[provided by RefSeq, Apr 2010]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

Multiple*

Mechanism· predicted

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?

1.02LOEUF

pLI 0.000

Z-score 1.51

OE 0.60 (0.37–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.31Z-score

OE missense 0.95 (0.86–1.05)

264 obs / 278.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.37–1.02)

0≤0.351.4

Missense OE?0.95 (0.86–1.05)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 10 / 16.7Missense obs/exp: 264 / 278.4Syn Z: 0.32

Background carrier burden — how many people carry a rare variant somewhere in SYT12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

574 rare PASS variants

Rare truncating (LoF)

1 in 3,000

58 rare PASS variants

Rare synonymous (reference)

1 in 130

245 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SYT12. 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 3,100
South Asian	~43k	1 in 66	1 in 1,400
Remaining (unassigned)	~30k	1 in 66	≈ 1 in 9,900
European (Finnish)	~27k	1 in 210	≈ 1 in 13,000
Admixed American	~22k	1 in 83	1 in 1,700
African / African American	~21k	1 in 90	≈ 1 in 4,400
East Asian	~20k	1 in 60	1 in 2,300
Ashkenazi Jewish	~13k	1 in 320	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 110	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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓