IL31RA
protein-codinginterleukin 31 receptor A, the group of Interleukin receptors|Fibronectin type III domain containing
Gene summary
The protein encoded by this gene belongs to the type I cytokine receptor family. This receptor, with homology to gp130, is expressed on monocytes, and is involved in IL-31 signaling via activation of STAT-3 and STAT-5. It functions either as a monomer, or as part of a receptor complex with oncostatin M receptor (OSMR). Several alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Jun 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~71.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007101
Submitter: Orphanet
Inheritance Pattern: Unknown
Disease ID:MONDO:0013502
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0013502
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0013502
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Dermatologic
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 IL31RA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_139017.7. 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 | 1 | 10 | 2 | 13 | ||
| missense | 1 | 90 | 15 | 2 | 108 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 91 | 25 | 4 | 121 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_620586.3 | 15 | MANE Select | |
| Ensembl | ENSP00000498630.1 | 15 | MANE Select | |
| RefSeq | NP_001229565.1 | 15 | Standard | |
| RefSeq | NP_001229566.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- JAK-STAT-Core
Biological Process
- MAPK cascade
- glandular epithelial cell differentiation
- acute inflammatory response to antigenic stimulus
- defense response
- transmembrane receptor protein tyrosine kinase signaling pathway
Molecular Function
- transcription coactivator activity
- cytokine receptor activity
- protein kinase binding
- cytokine binding
Cellular Component
- plasma membrane
- external side of plasma membrane
- integral component of membrane
- cell junction
- axon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000447346
- Coding exons
- 15
- Length
- 71472
- Individuals with no LoFs
- 125680
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 68
- Defined
- 125748
- p
- 0.000270
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.824 | 353 | 399 | 0.884 | 0.0000219 | 5015 |
| Missense (PolyPhen) | 37 | 61.091 | 0.60566 | 826 | ||
| Synonymous | -0.404 | 155 | 149 | 1.04 | 0.00000880 | 1435 |
| Loss of Function | 1.38 | 29 | 38.2 | 0.759 | 0.00000202 | 446 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Associates with OSMR to form the interleukin-31 receptor which activates STAT3 and to a lower extent STAT1 and STAT5 (PubMed:11877449, PubMed:14504285, PubMed:15627637, PubMed:15194700). May function in skin immunity (PubMed:15184896). Mediates IL31-induced itch, probably in a manner dependent on cation channels TRPA1 and TRPV1 (By similarity). Positively regulates numbers and cycling status of immature subsets of myeloid progenitor cells in bone marrow in vivo and enhances myeloid progenitor cell survival in vitro (By similarity). {ECO:0000250|UniProtKB:Q8K5B1, ECO:0000269|PubMed:11877449, ECO:0000269|PubMed:14504285, ECO:0000269|PubMed:15184896, ECO:0000269|PubMed:15194700, ECO:0000269|PubMed:15627637}.;
- Disease
- DISEASE: Amyloidosis, primary localized cutaneous, 2 (PLCA2) [MIM:613955]: A primary amyloidosis characterized by localized cutaneous amyloid deposition. This condition usually presents with itching (especially on the lower legs) and visible changes of skin hyperpigmentation and thickening that may be exacerbated by chronic scratching and rubbing. Primary localized cutaneous amyloidosis is often divided into macular and lichen subtypes although many affected individuals often show both variants coexisting. Lichen amyloidosis characteristically presents as a pruritic eruption of grouped hyperkeratotic papules with a predilection for the shins, calves, ankles and dorsa of feet and thighs. Papules may coalesce to form hyperkeratotic plaques that can resemble lichen planus, lichen simplex or nodular prurigo. Macular amyloidosis is characterized by small pigmented macules that may merge to produce macular hyperpigmentation, sometimes with a reticulate or rippled pattern. In macular and lichen amyloidosis, amyloid is deposited in the papillary dermis in association with grouped colloid bodies, thought to represent degenerate basal keratinocytes. The amyloid deposits probably reflect a combination of degenerate keratin filaments, serum amyloid P component, and deposition of immunoglobulins. {ECO:0000269|PubMed:19690585}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.239
Intolerance Scores
- LoFtool
- 0.917
- RVIS EVS
- 0.65
- RVIS percentile EVS
- 84.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.444
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |