STX5

Chr 11AR

syntaxin 5

Also known as: CDG2AA, SED5, STX5A

NCBI Gene: 6811 ENSG00000162236 UniProt: Q13190 OMIM: 603189

STX5 encodes a syntaxin protein that mediates endoplasmic reticulum to Golgi transport and is involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain Golgi apparatus structure. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly. The gene is highly constrained against loss-of-function variants, suggesting complete loss of function is poorly tolerated.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the syntaxin or t-SNARE (target-SNAP receptor) family. These proteins are found on cell membranes and serve as the targets for v-SNAREs (vesicle-SNAP receptors), permitting specific synaptic vesicle docking and fusion. The encoded protein regulates endoplasmic reticulum to Golgi transport and plays a critical role in autophagy. Autoantibodies targeting the encoded protein may be a diagnostic marker for endometriosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Congenital disorder of glycosylation, type IIaaMIM #620454

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

0.40

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.40LOEUF

pLI 0.843

Z-score 3.43

OE 0.16 (0.07–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.40Z-score

OE missense 0.92 (0.82–1.04)

190 obs / 206.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.07–0.40)

0≤0.351.4

Missense OE?0.92 (0.82–1.04)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 3 / 19.3Missense obs/exp: 190 / 206.2Syn Z: -0.43

Background carrier burden — how many people carry a rare variant somewhere in STX5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 89

477 rare PASS variants

Rare truncating (LoF)

1 in 780

42 rare PASS variants

Rare synonymous (reference)

1 in 210

187 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for STX5. 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 110	1 in 1,000
South Asian	~43k	1 in 160	1 in 500
Remaining (unassigned)	~30k	1 in 97	1 in 1,100
European (Finnish)	~27k	1 in 400	1 in 2,500
Admixed American	~22k	1 in 120	1 in 820
African / African American	~21k	1 in 140	1 in 530
East Asian	~20k	1 in 140	1 in 1,800
Ashkenazi Jewish	~13k	1 in 270	≈ 1 in 3,600
Middle Eastern	~2,884	1 in 280	≈ 1 in 2,500

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 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓