LRRC32 (Leucine Rich Repeat Containing 32)
GARP (Glycoprotein A Repetitions Predominant) – Key Regulator of TGF-β Activation and Immune Homeostasis
Gene Information Card
| Symbol | LRRC32 |
|---|---|
| Full Name | Leucine Rich Repeat Containing 32 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.5 |
| NCBI Gene ID | 2615 ncbi.nlm.nih.gov/gene/2615 |
| Ensembl ID | ENSG00000137507 |
| UniProt ID | Q14392 |
| OMIM ID | 137207 |
| HGNC ID | HGNC:6717 |
| Aliases | GARP, D11S833E, GARPIN, PVRIN |
Description
LRRC32 (Leucine Rich Repeat Containing 32), commonly known as GARP (Glycoprotein A Repetitions Predominant), encodes a transmembrane protein that functions as a receptor for latent TGF-β. It is predominantly expressed on the surface of activated regulatory T cells (Tregs) and platelets. LRRC32 binds latent TGF-β and presents it for activation, thereby playing a critical role in immune suppression, tolerance, and modulation of inflammatory responses. The gene is located on chromosome 11q13.5 and is highly conserved across species.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | LRRC32 expression on Tregs promotes TGF-β activation, contributing to immune evasion and tumor progression | Multiple studies in COSMIC and PubMed show overexpression in breast, colorectal, and lung cancers |
| Autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis) | Altered LRRC32 expression may disrupt Treg-mediated suppression, leading to loss of immune tolerance | ClinVar and OMIM entries associate LRRC32 variants with autoimmune susceptibility |
| Infectious diseases (e.g., HIV, tuberculosis) | LRRC32-mediated TGF-β activation can dampen anti-pathogen immune responses | Reported in literature; not yet curated in major databases |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Lung | 8.2 | Low |
| Colon | 6.1 | Low |
| Breast | 4.3 | Low |
| Whole blood | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High (overexpression model) |
| Jurkat (T-cell line) | 9.8 | Moderate (activated Treg-like) |
| K562 | 2.1 | Low |
| MCF7 | 1.5 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112C>T (p.Arg38Cys) | Missense | Rare (<0.01%) | Unknown functional impact; reported in ClinVar |
| c.454G>A (p.Gly152Ser) | Missense | Rare (<0.01%) | Predicted benign by computational tools |
| c.789+1G>A | Splice donor | Very rare | Likely loss-of-function; not confirmed in population studies |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations have been reported in LRRC32. Splice variants may reduce protein expression but are not validated.
Gain of Function (GOF)
No gain-of-function mutations have been described. Overexpression in Tregs is associated with enhanced TGF-β activation and immune suppression.
Dominant Negative (DN)
No dominant-negative mutations have been reported for LRRC32.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TGF-beta signaling pathway (Reactome: R-HSA-170834)
• Regulation of activated Tregs (KEGG: hsa04659)
Protein Summary
The LRRC32 protein (GARP) is a type I transmembrane glycoprotein containing multiple leucine-rich repeats. It is expressed on the surface of activated regulatory T cells and platelets. GARP binds latent TGF-β (LAP-TGF-β) and presents it for proteolytic or integrin-mediated activation, thereby controlling TGF-β bioavailability. This mechanism is essential for Treg-mediated immune suppression. The protein is also implicated in cancer immune evasion and autoimmune regulation. Its structure includes a large extracellular domain, a transmembrane helix, and a short cytoplasmic tail.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LRRC32 Knockout HEK293 Cell Line | EDJ-KQ4681 | Human | 2615 | Details Get a Quote |
| LRRC32 Knockout HeLa Cell Line | EDJ-KQ27384 | Human | 2615 | Details Get a Quote |
| LRRC32 Knockout A-549 Cell Line | EDJ-KQ61789 | Human | 2615 | Details Get a Quote |
| LRRC32 Knockout HCT 116 Cell Line | EDJ-KQ70270 | Human | 2615 | Details Get a Quote |
