IGSF11

Chr 3

immunoglobulin superfamily member 11

Also known as: BT-IgSF, BTIGSF, CT119, CXADRL1, Igsf13, VSIG3

NCBI Gene: 152404 ENSG00000144847 UniProt: Q5DX21 OMIM: 608351

IGSF11 is an immunoglobulin (Ig) superfamily member that is preferentially expressed in brain and testis. It shares significant homology with coxsackievirus and adenovirus receptor (CXADR; MIM 602621) and endothelial cell-selective adhesion molecule (ESAM).[supplied by OMIM, Apr 2005]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.79

Clinical Summary— IGSF11

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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

53 VUS of 63 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.001

Z-score 2.24

OE 0.44 (0.25–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.21Z-score

OE missense 0.78 (0.69–0.88)

184 obs / 236.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.25–0.79)

0≤0.351.4

Missense OE?0.78 (0.69–0.88)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 8 / 18.4Missense obs/exp: 184 / 236.3Syn Z: -1.26

This gene — mechanism propensity

0.80top 10%

GOF

0.76top 25%

LOF

0.2969th %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

63 submitted variants in ClinVar

ClinVar

Classification Summary

VUS53

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	53	53
Likely Benign	0	0
Benign	0	0
Total	53	53

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 IGSF11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →