ITGB8

Chr 7

integrin subunit beta 8

NCBI Gene: 3696ENSG00000105855UniProt: P26012

This gene is a member of the integrin beta chain family and encodes a single-pass type I membrane protein with a VWFA domain and four cysteine-rich repeats. This protein noncovalently binds to an alpha subunit to form a heterodimeric integrin complex. In general, integrin complexes mediate cell-cell and cell-extracellular matrix interactions and this complex plays a role in human airway epithelial proliferation. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

139
ClinVar variants
36
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— ITGB8
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 99 VUS of 139 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.26LOEUF
pLI 0.998
Z-score 5.11
OE 0.13 (0.07–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.93Z-score
OE missense 0.87 (0.80–0.95)
363 obs / 416.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.07–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.80–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 5 / 39.8Missense obs/exp: 363 / 416.5Syn Z: 0.57

ClinVar Variant Classifications

139 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic2
VUS99
Likely Benign3
Benign1
34
Pathogenic
2
Likely Pathogenic
99
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
2
0
2
VUS
0
94
5
0
99
Likely Benign
0
2
1
0
3
Benign
0
0
1
0
1
Total096430139

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

View in ClinVar →

Protein Context — Lollipop Plot

ITGB8 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
INTEGRIN, BETA-8; ITGB8
MIM #604160 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
APOE4 impairs the microglial response in Alzheimer's disease by inducing TGFβ-mediated checkpoints.
Yin Z et al.·Nat Immunol
2023
Investigating the inflammatory mechanism of notoginsenoside R1 in Diabetic nephropathy via ITGB8 based on network pharmacology and experimental validation.
Li C et al.·Mol Med
2024Functional
LGR6 modulates intervertebral disc degeneration through regulation of macrophage efferocytosis.
Li F et al.·J Transl Med
2025
MYO6 contributes to tumor progression and enzalutamide resistance in castration-resistant prostate cancer by activating the focal adhesion signaling pathway.
Zheng S et al.·Cell Commun Signal
2024
Circular RNA TTBK2 regulates cell proliferation, invasion and ferroptosis via miR-761/ITGB8 axis in glioma.
Zhang HY et al.·Eur Rev Med Pharmacol Sci
2020
Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer.
Qiu S et al.·Chin Med J (Engl)
2024Functional
The long non-coding RNA PVT1/miR-145-5p/ITGB8 axis regulates cell proliferation, apoptosis, migration and invasion in non-small cell lung cancer cells.
Wei CM et al.·Neoplasma
2020
Saffold virus exploits integrin αvβ8 and sulfated glycosaminoglycans as cooperative attachment receptors for infection.
Okuwa T et al.·Nat Commun
2025
ncRNA-mediated ITGB1 upregulation correlates with poor prognosis and tumor-immune infiltration in gastric cancer.
Li T et al.·Eur J Med Res
2025
A novel ITGB8 transcript variant sustains ovarian cancer cell survival through genomic instability and altered ploidy on a mutant p53 background.
Narayanan A et al.·J Ovarian Res
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Post Traumatic Stress DisorderComplex Posttraumatic Stress DisorderStress

Building Resilience at Schools: Emotional and Biological Assessment and Treatment of Traumatic Stress

RECRUITING
NCT05701111Phase NAStanford UniversityStarted 2024-02-23
Start with the Heart StudentsStart with the Heart TeachersCue Centered Therapy Counselors

External Resources

Links to major genomics databases and tools