STXBP2

Chr 19AR

syntaxin binding protein 2

Also known as: Hunc18b, MUNC18-2, UNC18-2, UNC18B, pp10122, unc-18B

NCBI Gene: 6813 ENSG00000076944 UniProt: Q15833 OMIM: 601717

The protein regulates cytotoxic granule exocytosis in natural killer cells by controlling SNARE complex assembly and vesicle fusion with membranes. Mutations cause familial hemophagocytic lymphohistiocytosis, an autosomal recessive disorder affecting the immune system. The gene is highly intolerant to loss-of-function variants (pLI near 0), consistent with severe disease when both copies are affected.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.841 OMIM phenotype

Clinical Summary— STXBP2

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Gene-Disease Validity (ClinGen)

familial hemophagocytic lymphohistiocytosis 5 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

116 unique Pathogenic / Likely Pathogenic· 465 VUS of 1401 total submissions

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GeneReview available — STXBP2

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.24

OE 0.56 (0.38–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.48Z-score

OE missense 0.93 (0.85–1.02)

344 obs / 370.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.38–0.84)

0≤0.351.4

Missense OE?0.93 (0.85–1.02)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 17 / 30.3Missense obs/exp: 344 / 370.0Syn Z: -1.15

ClinVar Variant Classifications

1401 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51

Likely Pathogenic65

VUS465

Likely Benign673

Benign63

Conflicting57

Pathogenic

Likely Pathogenic

465

VUS

673

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	44	5	2	0	51
Likely Pathogenic	51	10	4	0	65
VUS	9	402	45	9	465
Likely Benign	0	22	372	279	673
Benign	1	3	56	3	63
Conflicting	—				57
Total	105	442	479	291	1,374

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap STXBP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →