STXBP2

Chr 19AR

syntaxin binding protein 2

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
ARLOEUF 0.841 OMIM phenotype
Clinical SummarySTXBP2
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Gene-Disease Validity (ClinGen)
familial hemophagocytic lymphohistiocytosis 5 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 33 VUS of 100 total submissions
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GeneReview available — STXBP2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.24
OE 0.56 (0.380.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.48Z-score
OE missense 0.93 (0.851.02)
344 obs / 370.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.380.84)
00.351.4
Missense OE0.93 (0.851.02)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 17 / 30.3Missense obs/exp: 344 / 370.0Syn Z: -1.15

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS33
Likely Benign34
Conflicting1
5
Pathogenic
1
Likely Pathogenic
33
VUS
34
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
0
0
5
Likely Pathogenic
1
0
0
0
1
VUS
1
29
3
0
33
Likely Benign
0
2
25
7
34
Benign
0
0
0
0
0
Conflicting
1
Total73128774

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

View in ClinVar →

Protein Context — Lollipop Plot

STXBP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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