LRIG1

Chr 3

leucine rich repeats and immunoglobulin like domains 1

Also known as: LIG-1, LIG1

NCBI Gene: 26018ENSG00000144749UniProt: Q96JA1

Predicted to act upstream of or within several processes, including innervation; otolith morphogenesis; and sensory perception of sound. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

301
ClinVar variants
8
Pathogenic / LP
0.04
pLI score
0
Active trials
Clinical Summary— LRIG1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 224 VUS of 301 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.43LOEUF
pLI 0.035
Z-score 4.61
OE 0.26 (0.17–0.43)
Moderately constrained

More LoF-intolerant than ~75% 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.
-1.18Z-score
OE missense 1.13 (1.06–1.20)
719 obs / 635.6 exp
Tolerant

Tolerant to missense variation

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.0.26 (0.17–0.43)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.13 (1.06–1.20)
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.1.42
0≤1.21.6
LoF obs/exp: 12 / 45.6Missense obs/exp: 719 / 635.6Syn Z: -5.51

ClinVar Variant Classifications

301 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS224
Likely Benign41
Benign28
8
Pathogenic
224
VUS
41
Likely Benign
28
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
215
9
0
224
Likely Benign
0
20
2
19
41
Benign
0
18
2
8
28
Total02532127301

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

View in ClinVar →

Protein Context — Lollipop Plot

LRIG1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Macrophage-derived VISTA engages with LRIG1 and hinders gut epithelial repair in colitis.
Li M et al.·Cell Mol Immunol
2025
LRIG and cancer prognosis.
Lindquist D et al.·Acta Oncol
2014Review
LRIG1 expression and colorectal cancer prognosis.
Bakherad M et al.·BMC Med Genomics
2021
Expression of LRIG1 in pituitary tumor and its clinical significance.
Jie G et al.·Eur Rev Med Pharmacol Sci
2016
USP8 modulates ubiquitination of LRIG1 for Met degradation.
Oh YM et al.·Sci Rep
2014
LRIG1 is a prognostic biomarker in non-small cell lung cancer.
Kvarnbrink S et al.·Acta Oncol
2015
Lrig1 expression identifies airway basal cells with high proliferative capacity and restricts lung squamous cell carcinoma growth.
Succony L et al.·Eur Respir J
2022
Decreased LRIG1 in fulvestrant-treated luminal breast cancer cells permits ErbB3 upregulation and increased growth.
Morrison MM et al.·Oncogene
2016
LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer.
Thomasson M et al.·Int J Cancer
2011
LRIG1 gene copy number analysis by ddPCR and correlations to clinical factors in breast cancer.
Faraz M et al.·BMC Cancer
2020
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools