ITGA7

Chr 12AR

integrin subunit alpha 7

NCBI Gene: 3679 ENSG00000135424 UniProt: Q13683 OMIM: 600536

Integrin alpha-7 functions as a laminin receptor that is essential for skeletal muscle fiber anchorage, structural integrity, and myoblast migration during muscle development. Mutations cause autosomal recessive congenital muscular dystrophy due to ITGA7 deficiency, presenting in early infancy with muscle weakness and developmental delays. This gene is highly constrained against loss-of-function mutations, indicating its critical importance for normal muscle function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. They mediate a wide spectrum of cell-cell and cell-matrix interactions, and thus play a role in cell migration, morphologic development, differentiation, and metastasis. This protein functions as a receptor for the basement membrane protein laminin-1. It is mainly expressed in skeletal and cardiac muscles and may be involved in differentiation and migration processes during myogenesis. Defects in this gene are associated with congenital myopathy. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2009]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.801 OMIM phenotype

Clinical Summary— ITGA7

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

65 unique Pathogenic / Likely Pathogenic· 506 VUS of 1153 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?

0.80LOEUF

pLI 0.000

Z-score 2.82

OE 0.60 (0.46–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.36Z-score

OE missense 0.96 (0.90–1.03)

637 obs / 663.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.46–0.80)

0≤0.351.4

Missense OE?0.96 (0.90–1.03)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 36 / 59.5Missense obs/exp: 637 / 663.0Syn Z: 0.27

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateITGA7-related congenital muscular dystrophyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6552th %ile

GOF

0.6834th %ile

LOF

0.3163th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

1153 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29

Likely Pathogenic36

VUS506

Likely Benign460

Benign73

Conflicting31

Pathogenic

Likely Pathogenic

506

VUS

460

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	27	0	2	0	29
Likely Pathogenic	36	0	0	0	36
VUS	2	468	29	7	506
Likely Benign	0	11	207	242	460
Benign	1	4	58	10	73
Conflicting	—				31
Total	66	483	296	259	1,135

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap ITGA7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →