ITGA8

Chr 10AR

integrin subunit alpha 8

The integrin alpha-8 subunit forms heterodimeric integrin alpha8beta1 receptors that regulate recruitment of mesenchymal cells into epithelial structures during kidney development and mediate neurite outgrowth of sensory and motor neurons. Mutations cause autosomal recessive renal hypodysplasia/aplasia, a congenital kidney malformation disorder. The gene shows low constraint to loss-of-function variation (pLI near zero), consistent with its recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Renal hypodysplasia/aplasia 1MIM #191830
AR
0
Active trials
27
Pubs (1 yr)
43
P/LP submissions
5%
P/LP missense
0.66
LOEUF
LOF
Mechanism· G2P
Clinical SummaryITGA8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 unique Pathogenic / Likely Pathogenic· 214 VUS of 497 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.66LOEUF
pLI 0.000
Z-score 3.74
OE 0.49 (0.370.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.27Z-score
OE missense 1.03 (0.961.10)
593 obs / 574.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.49 (0.370.66)
00.351.4
Missense OE1.03 (0.961.10)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 31 / 63.0Missense obs/exp: 593 / 574.7Syn Z: -1.00
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongITGA8-related renal hypodysplasia/aplasiaLOFAR

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

DN
0.6939th %ile
GOF
0.6736th %ile
LOF
0.3066th %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

497 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic10
VUS214
Likely Benign120
Benign104
Conflicting3
27
Pathogenic
10
Likely Pathogenic
214
VUS
120
Likely Benign
104
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
21
0
27
Likely Pathogenic
7
1
2
0
10
VUS
1
200
12
1
214
Likely Benign
0
9
41
70
120
Benign
0
6
86
12
104
Conflicting
3
Total1321716283478

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

View in ClinVar →

Protein Context — Lollipop Plot

ITGA8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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