ITGA10

Chr 1

integrin subunit alpha 10

Also known as: PRO827

NCBI Gene: 8515 ENSG00000143127 OMIM: 604042

Integrins are integral transmembrane glycoproteins composed of noncovalently linked alpha and beta chains. They participate in cell adhesion as well as cell-surface mediated signalling. This gene encodes an integrin alpha chain and is expressed at high levels in chondrocytes, where it is transcriptionally regulated by AP-2epsilon and Ets-1. The protein encoded by this gene binds to collagen. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.79

Clinical Summary— ITGA10

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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

1 unique Pathogenic / Likely Pathogenic· 163 VUS of 170 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 0.000

Z-score 3.01

OE 0.61 (0.47–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.88Z-score

OE missense 0.90 (0.84–0.97)

587 obs / 650.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.47–0.79)

0≤0.351.4

Missense OE?0.90 (0.84–0.97)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 41 / 67.8Missense obs/exp: 587 / 650.2Syn Z: 0.86

This gene — mechanism propensity

0.6647th %ile

GOF

0.6931th %ile

LOF

0.2971th %ile

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

GOFprediction above median

DNprediction 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

170 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS163

Likely Benign4

Pathogenic

163

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	1
Likely Pathogenic	0	0	0	0
VUS	161	2	0	163
Likely Benign	3	0	1	4
Benign	0	0	0	0
Total	164	3	1	168

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

View in ClinVar →

134 pathogenic / likely-pathogenic (of 214) ClinVar copy-number / structural variants overlap ITGA10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →