ITGB6

Chr 2AR

integrin subunit beta 6

Also known as: AI1H

NCBI Gene: 3694 ENSG00000115221 UniProt: P18564 OMIM: 147558

This gene encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors that function in signaling from the extracellular matrix to the cell. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. The encoded protein forms a dimer with an alpha v chain and this heterodimer can bind to ligands like fibronectin and transforming growth factor beta 1. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Amelogenesis imperfecta, type IHMIM #616221

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Amelogenesis imperfecta, type IH; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.23

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.23LOEUF

pLI 0.000

Z-score 0.39

OE 0.93 (0.71–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.69Z-score

OE missense 1.09 (1.01–1.18)

478 obs / 437.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.93 (0.71–1.23)

0≤0.351.4

Missense OE?1.09 (1.01–1.18)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 35 / 37.6Missense obs/exp: 478 / 437.1Syn Z: -0.19

Background carrier burden — how many people carry a rare variant somewhere in ITGB6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

1,089 rare PASS variants

Rare truncating (LoF)

1 in 1,100

157 rare PASS variants

Rare synonymous (reference)

1 in 72

411 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ITGB6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 86	1 in 1,000
South Asian	~43k	1 in 49	1 in 970
Remaining (unassigned)	~30k	1 in 51	1 in 1,000
European (Finnish)	~27k	1 in 180	1 in 4,400
Admixed American	~22k	1 in 51	1 in 1,100
African / African American	~21k	1 in 46	1 in 1,300
East Asian	~20k	1 in 43	1 in 720
Ashkenazi Jewish	~13k	1 in 190	1 in 730
Middle Eastern	~2,884	1 in 43	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 15 coding exons well covered in gnomAD exomes; exons 7, 8, 15 marginal. Genomes: all 15.? see exons ↓