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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LRRC32
leucine rich repeat containing 32
Chromosome 11 · 11q13.5
NCBI Gene: 2615Ensembl: ENSG00000137507.12HGNC: HGNC:4161UniProt: Q14392
61PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingreceptor ligand inhibitor activitytransforming growth factor beta receptor signaling pathwayestablishment of protein localization to extracellular regioncleft palate, proliferative retinopathy, and developmental delayasthmaAllergyHepatitis
✦AI Summary

LRRC32 (leucine-rich repeat containing 32), also known as GARP (glycoprotein A repetitions predominant), is a key regulator of transforming growth factor beta (TGF-β) activation and latency. LRRC32 functions as a cell surface docking receptor that associates specifically with the latency-associated peptide (LAP) of TGF-β through disulfide bonds, maintaining TGF-β in an inactive state during extracellular storage 1. The protein outcompetes LTBP1 for LAP binding and regulates integrin-dependent TGF-β activation 1. LRRC32 is particularly important on regulatory T cells (Tregs), where it controls TGF-β1 surface activation and serves as a safeguard of the regulatory phenotype through positive feedback with FOXP3 2. Recent structural studies reveal that integrin αvβ8 binding induces dynamic allosteric conformational changes in latent TGF-β1-LRRC32 complexes, enabling receptor signaling without complete TGF-β release 3. LRRC32 expression is critical for epithelial fusion during palate development. Clinical relevance extends to cancer immunotherapy, where LRRC32 overexpression promotes immunosuppression; anti-GARP antibodies enhance CD8+ T cell function and overcome resistance to checkpoint blockade 4. LRRC32 is implicated in eosinophilic esophagitis and other immune-mediated diseases 5.

Sources cited
1
LRRC32 associates via disulfide bonds with LAP and regulates integrin-dependent TGF-β activation; outcompetes LTBP1 for LAP binding
PMID: 22278742
2
LRRC32 is a Treg-specific receptor binding latent TGF-β that safeguards FOXP3 and the regulatory phenotype via positive feedback
PMID: 20642442
3
Integrin αvβ8 binding induces dynamic allosteric changes in latent TGF-β1-LRRC32 complexes enabling receptor signaling without TGF-β release
PMID: 39288764
4
LRRC32 overexpression in cancers correlates with immunosuppression; anti-GARP antibodies enhance CD8+ T cell trafficking and overcome PD-1 blockade resistance
PMID: 36096533
5
LRRC32 is a disease-risk locus shared between eosinophilic esophagitis and other allergic diseases
PMID: 28224995
Disease Associationsⓘ21
cleft palate, proliferative retinopathy, and developmental delayOpen Targets
0.58Moderate
asthmaOpen Targets
0.53Moderate
AllergyOpen Targets
0.38Weak
HepatitisOpen Targets
0.35Weak
bacterial pneumoniaOpen Targets
0.32Weak
Herpes ZosterOpen Targets
0.31Weak
cleft palateOpen Targets
0.27Weak
atopic eczemaOpen Targets
0.27Weak
Eczematoid dermatitisOpen Targets
0.26Weak
dermatitisOpen Targets
0.26Weak
Global developmental delayOpen Targets
0.26Weak
VitreoretinopathyOpen Targets
0.26Weak
ulcerative colitisOpen Targets
0.23Weak
allergic diseaseOpen Targets
0.23Weak
inflammatory bowel diseaseOpen Targets
0.22Weak
allergic rhinitisOpen Targets
0.22Weak
Crohn's diseaseOpen Targets
0.22Weak
WheezingOpen Targets
0.21Weak
childhood onset asthmaOpen Targets
0.21Weak
lower respiratory tract diseaseOpen Targets
0.21Weak
Cleft palate, proliferative retinopathy, and developmental delayUniProt
Pathogenic Variants3
NM_001128922.2(LRRC32):c.84+14C>ALikely pathogenic
Cleft palate, proliferative retinopathy, and developmental delay
★☆☆☆2022
NM_001128922.2(LRRC32):c.980T>C (p.Ile327Thr)Likely pathogenic
Cleft palate, proliferative retinopathy, and developmental delay
☆☆☆☆2021→ Residue 327
NM_001128922.2(LRRC32):c.1630C>T (p.Arg544Ter)Pathogenic
Global developmental delay;Cleft palate;Vitreoretinopathy|Cleft palate, proliferative retinopathy, and developmental delay
☆☆☆☆2020→ Residue 544
View on ClinVar ↗
Related Genes
TGFB1Protein interaction100%TGFB3Protein interaction99%TGFB2Protein interaction96%EMSYProtein interaction72%WFIKKN2Shared pathway67%WFIKKN1Shared pathway67%
Tissue Expression6 tissues
Lung
100%
Heart
42%
Liver
16%
Ovary
13%
Brain
13%
Bone Marrow
8%
Gene Interaction Network
Click a node to explore
LRRC32TGFB1TGFB3TGFB2EMSYWFIKKN2WFIKKN1
PROTEIN STRUCTURE
Preparing viewer…
PDB8C7H · 2.70 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.70LoF Tolerant
pLIⓘ
0.59Intermediate
Observed/Expected LoF0.36 [0.19–0.70]
RankingsWhere LRRC32 stands among ~20K protein-coding genes
  • #7,571of 20,598
    Most Researched61
  • #4,044of 5,498
    Most Pathogenic Variants3
  • #5,362of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedLRRC32
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Dynamic allostery drives autocrine and paracrine TGF-β signaling.
PMID: 39288764
Cell · 2024
1.00
2
GARP on hepatic stellate cells is essential for the development of liver fibrosis.
PMID: 37348791
J Hepatol · 2023
0.90
3
Selective targeting of GARP-LTGFβ axis in the tumor microenvironment augments PD-1 blockade via enhancing CD8
PMID: 36096533
J Immunother Cancer · 2022
0.80
4
Genetics of eosinophilic esophagitis.
PMID: 28224995
Mucosal Immunol · 2017
0.70
5
FOXP3: required but not sufficient. the role of GARP (LRRC32) as a safeguard of the regulatory phenotype.
PMID: 20642442
Curr Mol Med · 2010
0.60