LRRC32
protein-codingleucine rich repeat containing 32
Gene summary
This gene encodes a type I membrane protein which contains 20 leucine-rich repeats. Alterations in the chromosomal region 11q13-11q14 are involved in several pathologies. [provided by RefSeq, Jul 2008]
- D11S833E
- GARP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0033641
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0033641
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LRRC32 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001128922.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 13 | 1 | 14 | |||
| missense | 1 | 120 | 13 | 1 | 135 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 3 | 120 | 26 | 2 | 151 |
Highest pathogenic variant AF is 0.0000013682848
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001122394.1 | 2 | MANE Select | |
| Ensembl | ENSP00000260061.5 | 2 | MANE Select | |
| RefSeq | NP_001357116.1 | 2 | Standard | |
| RefSeq | NP_001357117.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| lrrc32 | Danio rerio | Structure: thrombocyte Quality: distributed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- transforming growth factor beta receptor signaling pathway
- positive regulation of gene expression
- negative regulation of activated T cell proliferation
- negative regulation of cytokine secretion
- secondary palate development
Molecular Function
- protein binding
- transforming growth factor beta binding
Cellular Component
- extracellular space
- nucleoplasm
- integral component of plasma membrane
- cell surface
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000407242
- Coding exons
- 2
- Length
- 13224
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125748
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0889 | 393 | 398 | 0.987 | 0.0000256 | 4202 |
| Missense (PolyPhen) | 68 | 91.561 | 0.74267 | 1261 | ||
| Synonymous | -1.17 | 210 | 190 | 1.11 | 0.0000117 | 1526 |
| Loss of Function | 1.78 | 7 | 14.3 | 0.491 | 7.74e-7 | 148 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000064 | 0.000062 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space (PubMed:19750484, PubMed:19651619, PubMed:22278742). Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta (PubMed:22278742). Able to outcompete LTBP1 for binding to LAP regulatory chain of TGF-beta (PubMed:22278742). Controls activation of TGF-beta-1 (TGFB1) on the surface of activated regulatory T-cells (Tregs) (PubMed:19750484, PubMed:19651619). Required for epithelial fusion during palate development by regulating activation of TGF-beta-3 (TGFB3) (By similarity). {ECO:0000250|UniProtKB:G3XA59, ECO:0000269|PubMed:19651619, ECO:0000269|PubMed:19750484, ECO:0000269|PubMed:22278742}.;
Recessive Scores
- pRec
- 0.131
Intolerance Scores
- LoFtool
- 0.414
- RVIS EVS
- -1.21
- RVIS percentile EVS
- 5.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.412
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |