ITGBL1

Chr 13

integrin subunit beta like 1

Also known as: OSCP, TIED

NCBI Gene: 9358 ENSG00000198542 UniProt: O95965 OMIM: 604234

The encoded protein is a beta integrin-related protein containing integrin-like cysteine-rich repeats and belongs to the EGF-like protein family. This gene is not loss-of-function intolerant (pLI near 0, LOEUF 0.97), suggesting that heterozygous loss-of-function variants are likely tolerated in the general population. Currently, no well-established Mendelian diseases have been definitively associated with ITGBL1 mutations in the medical literature.

OMIM ResearchSummary from RefSeq

This gene encodes a beta integrin-related protein that is a member of the EGF-like protein family. The encoded protein contains integrin-like cysteine-rich repeats. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.97

Clinical Summary— ITGBL1

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.000

Z-score 1.67

OE 0.66 (0.45–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.58Z-score

OE missense 0.90 (0.81–1.00)

247 obs / 274.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.45–0.97)

0≤0.351.4

Missense OE?0.90 (0.81–1.00)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 18 / 27.5Missense obs/exp: 247 / 274.1Syn Z: 1.00

This gene — mechanism propensity

0.6355th %ile

GOF

0.6345th %ile

LOF

0.3355th %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.