ITGA6

Chr 2AR

integrin subunit alpha 6

Also known as: CD49f, ITGA6A, ITGA6B, JEB6, VLA-6

NCBI Gene: 3655 ENSG00000091409 UniProt: P23229 OMIM: 147556

The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 6 subunit. This subunit may associate with a beta 1 or beta 4 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. The alpha 6 beta 4 integrin may promote tumorigenesis, while the alpha 6 beta 1 integrin may negatively regulate erbB2/HER2 signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.531 OMIM phenotype

Clinical Summary— ITGA6

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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

57 unique Pathogenic / Likely Pathogenic· 263 VUS of 857 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ITGA6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.53LOEUF

pLI 0.000

Z-score 4.56

OE 0.37 (0.27–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.65Z-score

OE missense 0.81 (0.75–0.87)

463 obs / 574.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.27–0.53)

0≤0.351.4

Missense OE?0.81 (0.75–0.87)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 23 / 61.6Missense obs/exp: 463 / 574.0Syn Z: 0.95

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedITGA6-related epidermolysis bullosa with pyloric atresiaLOFAR

This gene — mechanism propensity

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

0.6648th %ile

GOF

0.6150th %ile

LOF

0.3258th %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.

Literature Evidence

DNHerein, we report a novel heterozygous missense mutation in the ITGB4 gene exerting a dominant negative effect that cosegregates with the EB phenotype in an extended family.1

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

References

1.PMID 26817667 ↗

ClinVar Variant Classifications

857 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34

Likely Pathogenic23

VUS263

Likely Benign406

Benign81

Conflicting23

Pathogenic

Likely Pathogenic

263

VUS

406

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	28	0	5	1	34
Likely Pathogenic	21	2	0	0	23
VUS	2	214	40	7	263
Likely Benign	1	6	182	217	406
Benign	0	6	71	4	81
Conflicting	—				23
Total	52	228	298	229	830

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap ITGA6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →