STX4

Chr 16AR

syntaxin 4

Also known as: DFNB123, STX4A, p35-2

NCBI Gene: 6810 ENSG00000103496 UniProt: Q12846 OMIM: 186591

STX4 encodes a plasma membrane t-SNARE protein that mediates docking and fusion of transport vesicles with the plasma membrane, including vesicles containing glucose transporters and neurotransmitter transporters. Mutations cause autosomal recessive nonsyndromic deafness (DFNB123), affecting auditory function. The gene shows low constraint against loss-of-function variants (LOEUF 1.158), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables sphingomyelin phosphodiesterase activator activity. Involved in several processes, including cornified envelope assembly; positive regulation of immune effector process; and positive regulation of protein localization. Located in several cellular components, including basolateral plasma membrane; cytoplasmic vesicle; and obsolete extracellular space. Part of SNARE complex. Is active in glutamatergic synapse and postsynapse. Implicated in autosomal recessive nonsyndromic deafness. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 123MIM #620745

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.16

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.16LOEUF

pLI 0.000

Z-score 1.06

OE 0.73 (0.47–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.11Z-score

OE missense 0.77 (0.66–0.88)

135 obs / 176.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.73 (0.47–1.16)

0≤0.351.4

Missense OE?0.77 (0.66–0.88)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 13 / 17.9Missense obs/exp: 135 / 176.4Syn Z: 0.16

Background carrier burden — how many people carry a rare variant somewhere in STX4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

478 rare PASS variants

Rare truncating (LoF)

1 in 1,700

66 rare PASS variants

Rare synonymous (reference)

1 in 420

190 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for STX4. 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 160	1 in 1,500
South Asian	~43k	1 in 130	1 in 3,800
Remaining (unassigned)	~30k	1 in 140	1 in 3,700
European (Finnish)	~27k	1 in 220	none seen
Admixed American	~22k	1 in 140	1 in 4,000
African / African American	~21k	1 in 130	1 in 2,700
East Asian	~20k	1 in 160	1 in 930
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 260	≈ 1 in 2,900

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): 9 of 10 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 10.? see exons ↓