TSPAN17

Chr 5

tetraspanin 17

Also known as: FBX23, FBXO23, TM4SF17

The protein is a tetraspanin that regulates ADAM10 metalloprotease trafficking and substrate specificity, particularly affecting VE-cadherin expression in endothelial cells and leukocyte transmigration. This gene is not highly constrained against loss-of-function variants and has not been definitively associated with human disease. Mutations in TSPAN17 have not been established as a cause of pediatric neurological disorders.

Summary from RefSeq, UniProt
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0
Active trials
0
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.02
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryTSPAN17
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
1.02LOEUF
pLI 0.000
Z-score 1.49
OE 0.63 (0.401.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.92Z-score
OE missense 0.81 (0.710.93)
158 obs / 194.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.63 (0.401.02)
00.351.4
Missense OE0.81 (0.710.93)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 12 / 19.0Missense obs/exp: 158 / 194.2Syn Z: 0.25
DN
0.84top 10%
GOF
0.83top 5%
LOF
0.1697th %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

TSPAN17 · protein map & ClinVar variants

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

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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