STX11

Chr 6AR

syntaxin 11

Also known as: FHL4, HLH4, HPLH4

STX11 encodes a SNARE protein that regulates vesicle transport between late endosomes and the trans-Golgi network. Mutations cause familial hemophagocytic lymphohistiocytosis type 4, a severe immunodeficiency disorder characterized by excessive immune activation and multi-organ involvement. The condition follows autosomal recessive inheritance and typically presents in infancy or early childhood.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.381 OMIM phenotype
Clinical SummarySTX11
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Gene-Disease Validity (ClinGen)
familial hemophagocytic lymphohistiocytosis 4 · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.38LOEUF
pLI 0.000
Z-score 0.81
OE 0.70 (0.381.38)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.13Z-score
OE missense 1.03 (0.921.15)
211 obs / 205.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.70 (0.381.38)
00.351.4
Missense OE1.03 (0.921.15)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 6 / 8.5Missense obs/exp: 211 / 205.7Syn Z: 0.15
DN
0.79top 25%
GOF
0.75top 25%
LOF
0.1796th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

STX11 · 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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