ITGA9

Chr 3

integrin subunit alpha 9

Also known as: ALPHA-RLC, ITGA4L, RLC

NCBI Gene: 3680 ENSG00000144668 UniProt: Q13797 OMIM: 603963

The protein forms an integrin receptor (alpha-9/beta-1) that mediates cell adhesion by binding to VCAM1, cytotactin, and osteopontin, and regulates vascular smooth muscle contraction by inhibiting calcium influx. Mutations cause autosomal recessive muscular dystrophy-limb girdle type 2S, which presents with progressive proximal muscle weakness and elevated creatine kinase levels. The gene is highly constrained against loss-of-function variants (LOEUF 0.42), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane glycoproteins composed of an alpha chain and a beta chain that mediate cell-cell and cell-matrix adhesion. The protein encoded by this gene, when bound to the beta 1 chain, forms an integrin that is a receptor for VCAM1, cytotactin and osteopontin. Expression of this gene has been found to be upregulated in small cell lung cancers. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.008

Z-score 4.99

OE 0.27 (0.18–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.63Z-score

OE missense 0.93 (0.86–0.99)

532 obs / 574.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.18–0.42)

0≤0.351.4

Missense OE?0.93 (0.86–0.99)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 15 / 54.9Missense obs/exp: 532 / 574.3Syn Z: -1.00

Background carrier burden — how many people carry a rare variant somewhere in ITGA9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 43

1,294 rare PASS variants

Rare truncating (LoF)

1 in 2,400

123 rare PASS variants

Rare synonymous (reference)

1 in 73

540 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ITGA9. 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 71	1 in 3,100
South Asian	~43k	1 in 35	1 in 2,000
Remaining (unassigned)	~30k	1 in 43	1 in 2,100
European (Finnish)	~27k	1 in 150	1 in 4,500
Admixed American	~22k	1 in 37	1 in 1,300
African / African American	~21k	1 in 37	1 in 1,500
East Asian	~20k	1 in 63	1 in 890
Ashkenazi Jewish	~13k	1 in 100	none seen
Middle Eastern	~2,884	1 in 46	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): 27 of 28 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 28.? see exons ↓