OSMR
protein-codingoncostatin M receptor, the group of Fibronectin type III domain containing
Gene summary
This gene encodes a member of the type I cytokine receptor family. The encoded protein heterodimerizes with interleukin 6 signal transducer to form the type II oncostatin M receptor and with interleukin 31 receptor A to form the interleukin 31 receptor, and thus transduces oncostatin M and interleukin 31 induced signaling events. Mutations in this gene have been associated with familial primary localized cutaneous amyloidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~99.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0024522
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0024522
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0024522
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0007101
Submitter: Orphanet
Inheritance Pattern: SD
Disease ID:MONDO:0024522
Submitter: Ambry Genetics
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 OSMR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003999.3. 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 | 2 | 8 | 5 | 15 | ||
| missense | 3 | 4 | 119 | 17 | 5 | 148 |
| nonsense | 1 | 4 | 5 | |||
| start loss | 0 | |||||
| frameshift | 3 | 2 | 5 | |||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 3 | 8 | 132 | 25 | 10 | 178 |
Highest pathogenic variant AF is 0.00018462462
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003990.1 | 17 | MANE Select | |
| Ensembl | ENSP00000274276.3 | 17 | MANE Select | |
| RefSeq | NP_001161827.1 | 6 | Standard | |
| RefSeq | NP_001310433.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Jak-STAT signaling pathway - Homo sapiens (human)
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- JAK-STAT-Core
- Oncostatin M Signaling Pathway
Biological Process
- positive regulation of acute inflammatory response
- positive regulation of cell population proliferation
- cytokine-mediated signaling pathway
- response to cytokine
- oncostatin-M-mediated signaling pathway
Molecular Function
- cytokine receptor activity
- oncostatin-M receptor activity
- protein binding
- growth factor binding
- cytokine binding
Cellular Component
- plasma membrane
- oncostatin-M receptor complex
- external side of plasma membrane
- apical plasma membrane
- receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000274276
- Coding exons
- 17
- Length
- 99739
- Individuals with no LoFs
- 125583
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 164
- Defined
- 125748
- p
- 0.000656
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.113 | 495 | 502 | 0.986 | 0.0000250 | 6489 |
| Missense (PolyPhen) | 112 | 107.46 | 1.0423 | 1524 | ||
| Synonymous | 0.281 | 182 | 187 | 0.974 | 0.0000100 | 1811 |
| Loss of Function | 1.87 | 34 | 48.0 | 0.709 | 0.00000247 | 561 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00095 | 0.00095 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00056 | 0.00055 | rare |
| South Asian | 0.0014 | 0.0014 | notable |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Associates with IL31RA to form the IL31 receptor. Binds IL31 to activate STAT3 and possibly STAT1 and STAT5. Capable of transducing OSM-specific signaling events. {ECO:0000269|PubMed:15184896, ECO:0000269|PubMed:8999038}.;
- Disease
- DISEASE: Amyloidosis, primary localized cutaneous, 1 (PLCA1) [MIM:105250]: 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:18179886, ECO:0000269|PubMed:19690585}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0866
Intolerance Scores
- LoFtool
- 0.958
- RVIS EVS
- 1.59
- RVIS percentile EVS
- 95.81
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.984
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |