STXBP3

Chr 1

syntaxin binding protein 3

Also known as: MUNC18-3, MUNC18C, PSP, UNC-18C

NCBI Gene: 6814 ENSG00000116266 OMIM: 608339

STXBP3 encodes a protein that binds syntaxins and regulates calcium-dependent exocytosis, including insulin-dependent GLUT4 vesicle transport in adipocytes and neutrophil degranulation. The gene shows extremely high constraint against loss-of-function variants (pLI nearly 1.0), suggesting that heterozygous mutations would likely cause dominant disease, though specific associated disorders have not yet been established. Clinical presentations would likely involve metabolic dysfunction given the protein's role in glucose transport regulation.

OMIM ResearchSummary from RefSeq, UniProt

Enables syntaxin binding activity. Involved in negative regulation of calcium ion-dependent exocytosis; neutrophil degranulation; and platelet aggregation. Located in cytosol; plasma membrane; and secretory granule. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.59

Clinical Summary— STXBP3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 61 VUS of 93 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.000

Z-score 3.49

OE 0.38 (0.25–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.76Z-score

OE missense 0.71 (0.64–0.80)

216 obs / 302.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.25–0.59)

0≤0.351.4

Missense OE?0.71 (0.64–0.80)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 14 / 36.9Missense obs/exp: 216 / 302.3Syn Z: 1.18

ClinVar Variant Classifications

93 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic3

VUS61

Likely Benign2

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	2	1	3
VUS	1	60	61
Likely Benign	0	2	2
Benign	0	0	0
Total	3	63	66

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap STXBP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →