OSMR

Summary

OSMR (oncostatin M receptor, HGNC:8507) is a protein-coding gene on chromosome 5p13.1, encoding Oncostatin-M-specific receptor subunit beta (Q99650). Associates with IL31RA to form the IL31 receptor.

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.

Source: NCBI Gene 9180 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyloidosis, primary localized cutaneous, 1 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 24
• Clinical variants (ClinVar): 216 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes
• MANE Select transcript: NM_003999

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8507
Approved symbol	OSMR
Name	oncostatin M receptor
Location	5p13.1
Locus type	gene with protein product
Status	Approved
Aliases	OSMRB, OSMRbeta
Ensembl gene	ENSG00000145623
Ensembl biotype	protein_coding
OMIM	601743
Entrez	9180

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 nonsense_mediated_decay

ENST00000274276, ENST00000502536, ENST00000508882, ENST00000509237, ENST00000513831, ENST00000880313, ENST00000880314, ENST00000880315, ENST00000959611

RefSeq mRNA: 5 — MANE Select: NM_003999 NM_001168355, NM_001323504, NM_001323505, NM_001323506, NM_003999

CCDS: CCDS3928, CCDS54847

Canonical transcript exons

ENST00000274276 — 18 exons

Exon	Start	End
ENSE00000971344	38876201	38876373
ENSE00000971345	38881593	38881764
ENSE00000971346	38883827	38884111
ENSE00000971347	38885349	38885484
ENSE00000971348	38886039	38886190
ENSE00000971350	38903882	38904024
ENSE00000971351	38904353	38904503
ENSE00000971352	38917546	38917622
ENSE00000971353	38918840	38919062
ENSE00000971355	38921615	38921794
ENSE00000971356	38923150	38923254
ENSE00000971357	38924422	38924595
ENSE00000971358	38925204	38925371
ENSE00000971359	38931883	38931964
ENSE00000971360	38932463	38932535
ENSE00000971361	38932872	38935641
ENSE00002058545	38846012	38846387
ENSE00002388515	38869032	38869117

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.1910 / max 425.4799, expressed in 1396 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56198	30.7499	1377
56197	1.7388	970
56199	0.4848	326
56196	0.2175	104

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	99.09	gold quality
saphenous vein	UBERON:0007318	97.08	gold quality
cartilage tissue	UBERON:0002418	96.51	gold quality
tibia	UBERON:0000979	96.08	gold quality
lower lobe of lung	UBERON:0008949	95.63	gold quality
heart right ventricle	UBERON:0002080	95.02	gold quality
peritoneum	UBERON:0002358	94.30	gold quality
omental fat pad	UBERON:0010414	94.30	gold quality
visceral pleura	UBERON:0002401	94.22	gold quality
parietal pleura	UBERON:0002400	94.03	gold quality
superficial temporal artery	UBERON:0001614	93.82	gold quality
stromal cell of endometrium	CL:0002255	93.61	gold quality
descending thoracic aorta	UBERON:0002345	93.50	gold quality
upper lobe of lung	UBERON:0008948	93.48	gold quality
tibial artery	UBERON:0007610	93.37	gold quality
popliteal artery	UBERON:0002250	93.36	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.33	gold quality
upper lobe of left lung	UBERON:0008952	93.33	gold quality
aorta	UBERON:0000947	93.17	gold quality
pleura	UBERON:0000977	93.12	gold quality
right coronary artery	UBERON:0001625	93.07	gold quality
thoracic aorta	UBERON:0001515	92.96	gold quality
ascending aorta	UBERON:0001496	92.93	gold quality
right lung	UBERON:0002167	92.63	gold quality
urethra	UBERON:0000057	92.27	gold quality
left coronary artery	UBERON:0001626	92.24	gold quality
coronary artery	UBERON:0001621	92.21	gold quality
synovial joint	UBERON:0002217	92.20	gold quality
germinal epithelium of ovary	UBERON:0001304	92.05	gold quality
left uterine tube	UBERON:0001303	91.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.92
E-MTAB-6386	no	274.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

112 targeting OSMR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 40)

• expression and evidence for STAT3 activation in human ovarian carcinomas (PMID:12061840)
• The expression of OSM and its receptor in ovarian tissue from fetuses and women suggests a possible role of OSM in growth initiation of human primordial follicles. (PMID:15831292)
• sOSMR is able to bind OSM and interleukin-31 when associated to soluble gp130 or soluble interleukin-31R, respectively, and to neutralize both cytokine properties (PMID:17028186)
• FPLCA has been mapped to 5p13.1-q11.2, and by candidate gene analysis, study identified missense mutations in the OSMR gene, encoding oncostatin M-specific receptor beta (OSMRbeta), in three families. (PMID:18179886)
• murine OSMR initiates STAT5 activation directly via the receptor bound Janus kinases. Intriguingly, the murine receptor preferentially recruits JAK2, whereas the human receptor seems to have a higher affinity for JAK1. (PMID:18430728)
• IL-6 and Oncostatin M individually affect the profile of leukocyte trafficking (PMID:18641356)
• The renal parenchyma is capable of generating a strong acute phase response, likely mediated via OSM/OSMR. (PMID:19158344)
• Epigenetic silencing and DNA methylation of OSMR is associated with colorectal cancers. (PMID:19223499)
• study reporta a Japanese family with familial primary localized cutaneous amyloidosis in whom a novel OSMR mutation was observed (PMID:19375894)
• study provides evidence for the existence of a novel pathogenic mutation in the OSMR gene in a caucasian family with familial primary cutaneous amyloidosis (PMID:19466957)
• provides a biologic rationale for silencing of OSMR in colon cancer progression and highlight a new therapeutic target. Moreover, detection and quantification of OSMR promoter methylation in fecal DNA is a highly specific diagnostic biomarker for CRC (PMID:19662090)
• The identification of OSMR and IL31RA gene pathology provides an explanation of the high prevalence of primary cutaneous amyloidosis in Taiwan as well as new insight into disease pathophysiology. (PMID:19690585)
• Two new pathogenic heterozygous missense mutations in the OSMR gene (p.Val631Leu and p.Asp647Tyr) were identified in two Dutch familial primary localized cutaneous amyloidosis families. (PMID:20507362)
• An alternatively spliced variant of OSMR transcribing a soluble form of this receptor has been characterized in esophageal squamous cell carcinoma. (PMID:21394648)
• Aberrant methylation of the OSMR gene is associated with non-invasive colorectal cancer. (PMID:21508378)
• We conclude that OSMR overexpression in cervical SCC cells provides increased sensitivity to OSM, which induces pro-malignant changes. (PMID:21952923)
• This study identified a new heterozygous OSMR missense mutation in primary localized cutaneous amyloidosis. (PMID:22062952)
• enhanced production by beta-defensin-2 in T cells (PMID:22137028)
• A unique loop structure in oncostatin M determines binding affinity toward oncostatin M receptor and leukemia inhibitory factor receptor. (PMID:22829597)
• We conclude that an OSMR/TGM2/integrin-alpha5beta1/fibronectin pathway is of biological significance in cervical squamous cell carcinoma (PMID:23765377)
• The disease severity of rheumatoid arthritis and systemic lupus erythematosus can be partially affected by the OSMR promoter polymorphisms. (PMID:24219225)
• oncostatin M is a cytokine possessing vigorous antiviral and immunostimulatory properties which is released by APC upon interaction with CD40L present on activated CD4+ T cells. (PMID:24418171)
• primary localized cutaneous amyloidosis has a missense mutation in oncostatin M receptor beta (PMID:25054142)
• The interleukin IL-31/IL-31receptor axis contributes to tumor growth in human follicular lymphoma. (PMID:25283844)
• this study offers new findings on the molecular genetics and disease relevance of mutations in OSMR in Familial primary localized cutaneous amyloidosis. (PMID:25792357)
• Oncostatin M and interleukin-31: Cytokines, receptors, signal transduction and physiology. (PMID:26198770)
• OSMRBeta in neurons is critical for neuronal survival during cerebral ischemic/reperfusion. (PMID:26311783)
• the RET p.S891A mutation combined with OSMR p.G513D may underlie a novel phenotype manifesting as familial medullary thyroid carcinoma and cutaneous amyloidosis (PMID:26356818)
• OSM:OSMR interactions are able to induce EMT, increased cancer stem cell-like properties and enhanced lung colonisation in SCC cells (PMID:27351213)
• OSMR-beta deficiency in macrophages improved high-fat diet-induced atherogenesis and plaque vulnerability (PMID:28258089)
• OSM and OSMR are highly expressed in inflammatory bowel disease intestinal mucosa compared to control mucosa. Intestinal stromal cells express abundant OSMR. (PMID:28368383)
• The PLAC1 expression has been demonstrated for the first time in cervical cancers. This preliminary study has further revealed a complex relationship between PLAC1 expression, cervical cancer histologic type, p53, and HPV type that requires further investigation. (PMID:28375929)
• Missense mutatios were found in exon 10 of the oncostatin-M specific receptor beta subunit (OSMR) gene in all of the six patients from family 1, and in exon 14 of the OSMR gene in all of the four patients from family 2. (PMID:29419851)
• substitution of the AB loop and D-helix in LIF with their OSM counterparts was sufficient for OSMR activation (PMID:29511087)
• Polymorphisms of the OSMR rs2292016 locus are related to the development and outcome of DCM. (PMID:29652994)
• The current study suggested that the OSMR gene is highly expressed in human chronic autoimmune urticaria (CAU) skin tissues, and cause the up-regulation of the JAK/STAT3 signaling pathway-related genes. OSMR gene silencing in mice inhibits the activation of the JAK/STAT3 signaling pathway, thereby suppressing the development of CAU. (PMID:30134804)
• Overexpression of LINC00520 contributes to the aggravation of Acute kidney injury by targeting miR-27b-3p/ OSMR. (PMID:30684280)
• The present data indicate OSMR mutations as not only the main cause of fPLCA, but also the potential source of the pathogenesis of sPLCA, although the exact molecular mechanism remains unknown. (PMID:30734345)
• OSMR genotype frequencies were found to be associated with higher recurrence in bladder cancer, and it may serve as a biomarker candidate gene to predict prognosis of this disease. (PMID:30755233)
• High OSMR expression is associated with metastasis in gastric cancer. (PMID:30778797)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ghrb	ENSDARG00000007671
danio_rerio	il11ra	ENSDARG00000026736
danio_rerio	lifrb	ENSDARG00000039863
danio_rerio	ghra	ENSDARG00000054771
danio_rerio	lifra	ENSDARG00000098857
danio_rerio	il6r	ENSDARG00000104474
mus_musculus	Osmr	ENSMUSG00000022146
rattus_norvegicus	Osmr	ENSRNOG00000033192

Paralogs (23): CRLF1 (ENSG00000006016), IL12RB2 (ENSG00000081985), IL5RA (ENSG00000091181), IL12RB1 (ENSG00000096996), IL27RA (ENSG00000104998), EBI3 (ENSG00000105246), GHR (ENSG00000112964), PRLR (ENSG00000113494), LIFR (ENSG00000113594), LEPR (ENSG00000116678), CSF3R (ENSG00000119535), CNTFR (ENSG00000122756), IL13RA2 (ENSG00000123496), IL13RA1 (ENSG00000131724), IL6ST (ENSG00000134352), IL11RA (ENSG00000137070), IL2RG (ENSG00000147168), IL6R (ENSG00000160712), IL23R (ENSG00000162594), IL31RA (ENSG00000164509), IL3RA (ENSG00000185291), CSF2RA (ENSG00000198223), CRLF2 (ENSG00000205755)

Protein

Protein identifiers

Oncostatin-M-specific receptor subunit beta — Q99650 (reviewed: Q99650)

Alternative names: Interleukin-31 receptor subunit beta

All UniProt accessions (4): Q99650, H0Y8W9, H0Y9E3, H0YAD1

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Heterodimer composed of OSMR and IL6ST (type II OSM receptor). Heterodimer with IL31RA to form the IL31 receptor.

Subcellular location. Membrane.

Tissue specificity. Expressed in keratinocytes (at protein level). Expressed at relatively high levels in all neural cells as well as fibroblast and epithelial cells.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. The box 1 motif is required for JAK interaction and/or activation.

Induction. Activated by oncostatin-M. Up-regulated by IFNG/IFN-gamma. Up-regulated by bacterial lipopolysaccharides (LPS). Up-regulated by triacylated lipoprotein (Pam3Cys).

Similarity. Belongs to the type I cytokine receptor family. Type 2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99650-1	1	yes
Q99650-2	2

RefSeq proteins (5): NP_001161827, NP_001310433, NP_001310434, NP_001310435, NP_003990* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003529	Hematopoietin_rcpt_Gp130_CS	Conserved_site
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR040817	LIFR_D2	Domain
IPR048497	LIF-R-like_Ig-like	Domain
IPR052672	Type1_Cytokine_Rcpt_Type2	Family

Pfam: PF00041, PF17971, PF21177, PF25552

UniProt features (32 total): sequence variant 11, glycosylation site 5, domain 4, short sequence motif 2, modified residue 2, splice variant 2, topological domain 2, signal peptide 1, chain 1, disulfide bond 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99650-F1	74.07	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 826, 889

Disulfide bonds (1): 245–255

Glycosylation sites (5): 163, 326, 380, 446, 580

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6788467	IL-6-type cytokine receptor ligand interactions

MSigDB gene sets: 253 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, ACTACCT_MIR196A_MIR196B, YAGI_AML_WITH_INV_16_TRANSLOCATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_RESPONSE_TO_PEPTIDE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MENSE_HYPOXIA_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOCC_CELL_SURFACE

GO Biological Process (5): positive regulation of acute inflammatory response (GO:0002675), positive regulation of cell population proliferation (GO:0008284), cytokine-mediated signaling pathway (GO:0019221), response to cytokine (GO:0034097), oncostatin-M-mediated signaling pathway (GO:0038165)

GO Molecular Function (6): cytokine receptor activity (GO:0004896), ciliary neurotrophic factor receptor binding (GO:0005127), growth factor binding (GO:0019838), cytokine binding (GO:0019955), oncostatin-M receptor activity (GO:0004924), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), type I oncostatin-M receptor complex (GO:0005900), external side of plasma membrane (GO:0009897), apical plasma membrane (GO:0016324), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-6 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytokine-mediated signaling pathway	2
protein binding	2
acute inflammatory response	1
regulation of acute inflammatory response	1
positive regulation of inflammatory response	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
response to peptide	1
transmembrane signaling receptor activity	1
cytokine binding	1
immune receptor activity	1
cytokine receptor binding	1
cytokine receptor activity	1
oncostatin-M-mediated signaling pathway	1
binding	1
membrane	1
cell periphery	1
plasma membrane signaling receptor complex	1
plasma membrane	1
cell surface	1
side of membrane	1
apical part of cell	1
plasma membrane region	1
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1453 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSMR	OSM	P13725	998
OSMR	IL31	Q6EBC2	995
OSMR	IL31RA	Q8NI17	989
OSMR	SHC1	P29353	888
OSMR	CTF1	Q16619	863
OSMR	IL11	P20809	845
OSMR	JAK1	P23458	843
OSMR	LIFR	P42702	813
OSMR	CNTF	P26441	802
OSMR	IL6	P05231	800
OSMR	LIF	P15018	797
OSMR	IL6ST	P40189	761
OSMR	CNTFR	P26992	746
OSMR	ERBB2	P04626	692
OSMR	IL6R	P08887	682

IntAct

108 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
OSMR	JAK1	psi-mi:“MI:0914”(association)	0.560
OSMR	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
LHX2	OSMR	psi-mi:“MI:0915”(physical association)	0.560
OSMR	GPRC5D	psi-mi:“MI:0915”(physical association)	0.560
SGTB	OSMR	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	OSMR	psi-mi:“MI:0915”(physical association)	0.560
OSMR	JAK1	psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
MRAP2	PODXL	psi-mi:“MI:0914”(association)	0.530
DLK1	SCAMP3	psi-mi:“MI:0914”(association)	0.530
TMEM200A	STX6	psi-mi:“MI:0914”(association)	0.530
MANSC1	SMPD2	psi-mi:“MI:0914”(association)	0.530
CTLA4	B4GALT5	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
PCDHA3	CYP51A1	psi-mi:“MI:0914”(association)	0.530
OSMR	HSPA9	psi-mi:“MI:0915”(physical association)	0.500
OSMR	NDUFS2	psi-mi:“MI:0914”(association)	0.500
OSMR	NDUFS1	psi-mi:“MI:0915”(physical association)	0.500
OSMR	NDUFS2	psi-mi:“MI:0915”(physical association)	0.500
OSMR	ATP5IF1	psi-mi:“MI:0915”(physical association)	0.460

BioGRID (75): OSMR (Affinity Capture-MS), OSMR (Affinity Capture-MS), ERBB2 (Co-localization), EGFR (Affinity Capture-Western), OSM (Reconstituted Complex), JAK1 (Affinity Capture-MS), ANKLE2 (Affinity Capture-MS), OSMR (Affinity Capture-RNA), OSMR (Protein-RNA), OSMR (Two-hybrid), OSMR (Two-hybrid), OSMR (Two-hybrid), UBQLN2 (Two-hybrid), SGTB (Two-hybrid), OSMR (Affinity Capture-MS)

ESM2 similar proteins: A2AED3, B0CLX4, B2RU80, B3DK56, B3EX02, E2RK30, F1NWE3, O14522, O70458, O70535, O88488, P08922, P08941, P08F94, P0C5E4, P17948, P20352, P23467, P28827, P28828, P35822, P35969, P35992, P42702, P42703, P53767, P97378, Q15262, Q2EY13, Q2EY15, Q2VWP7, Q2VWP9, Q589G5, Q5RFR6, Q5VJ70, Q5VTL7, Q5XNR9, Q62959, Q63132, Q65Z14

Diamond homologs: O70458, P42702, P42703, Q5XNR9, Q65Z14, Q99650, O70535, P97603, P97798, Q92859, B3EX02

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IL31	up-regulates	OSMR	binding
OSM	up-regulates	OSMR	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

216 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	134
Likely benign	25
Benign	13

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
30220	NM_003999.3(OSMR):c.1940A>T (p.Asp647Val)	Pathogenic
30222	NM_003999.3(OSMR):c.2090A>C (p.Lys697Thr)	Pathogenic
7809	NM_003999.3(OSMR):c.1853G>C (p.Gly618Ala)	Pathogenic
7808	NM_003999.3(OSMR):c.2072T>C (p.Ile691Thr)	Likely pathogenic

SpliceAI

3778 predictions. Top by Δscore:

Variant	Effect	Δscore
5:38876199:A:AG	acceptor_gain	1.0000
5:38876200:G:GG	acceptor_gain	1.0000
5:38881755:G:GT	donor_gain	1.0000
5:38881762:GTG:G	donor_gain	1.0000
5:38883825:A:AG	acceptor_gain	1.0000
5:38883826:G:GG	acceptor_gain	1.0000
5:38883826:GT:G	acceptor_gain	1.0000
5:38883826:GTA:G	acceptor_gain	1.0000
5:38883826:GTAC:G	acceptor_gain	1.0000
5:38883826:GTACA:G	acceptor_gain	1.0000
5:38884112:G:GG	donor_gain	1.0000
5:38885341:AT:A	acceptor_gain	1.0000
5:38885342:T:G	acceptor_gain	1.0000
5:38885445:G:GA	donor_gain	1.0000
5:38885480:GAATC:G	donor_gain	1.0000
5:38885485:G:GG	donor_gain	1.0000
5:38904342:T:A	acceptor_gain	1.0000
5:38904500:GCTG:G	donor_gain	1.0000
5:38917544:A:AG	acceptor_gain	1.0000
5:38917545:G:GA	acceptor_gain	1.0000
5:38919061:CA:C	donor_gain	1.0000
5:38919063:G:GG	donor_gain	1.0000
5:38931876:C:CA	acceptor_gain	1.0000
5:38931881:A:AG	acceptor_gain	1.0000
5:38931882:G:GG	acceptor_gain	1.0000
5:38931882:GCCTC:G	acceptor_gain	1.0000
5:38931962:GTG:G	donor_gain	1.0000
5:38932458:TCTA:T	acceptor_loss	1.0000
5:38932460:TAG:T	acceptor_loss	1.0000
5:38932461:A:AG	acceptor_gain	1.0000

AlphaMissense

6508 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:38885416:G:C	W257C	0.994
5:38885416:G:T	W257C	0.994
5:38885414:T:A	W257R	0.989
5:38885414:T:C	W257R	0.989
5:38885408:T:A	C255S	0.986
5:38885409:G:C	C255S	0.986
5:38904461:T:A	W415R	0.985
5:38904461:T:C	W415R	0.985
5:38876281:T:A	W52R	0.982
5:38876281:T:C	W52R	0.982
5:38904463:G:C	W415C	0.981
5:38904463:G:T	W415C	0.981
5:38885378:T:A	C245S	0.979
5:38885379:G:C	C245S	0.979
5:38904432:G:C	R405P	0.977
5:38924486:G:C	W645C	0.977
5:38924486:G:T	W645C	0.977
5:38881665:T:C	C107R	0.976
5:38881665:T:A	C107S	0.974
5:38881666:G:C	C107S	0.974
5:38885408:T:C	C255R	0.974
5:38886128:T:C	L310P	0.974
5:38884051:T:A	C215S	0.973
5:38884052:G:C	C215S	0.973
5:38883909:T:G	C167W	0.972
5:38885378:T:C	C245R	0.972
5:38885379:G:A	C245Y	0.972
5:38903947:T:A	W353R	0.972
5:38903947:T:C	W353R	0.972
5:38921670:G:C	W547C	0.971

dbSNP variants (sampled 300 via entrez): RS1000032944 (5:38865979 C>T), RS1000087677 (5:38910764 A>G), RS1000122568 (5:38864415 T>G), RS1000154714 (5:38916201 G>A,T), RS1000156871 (5:38909408 A>G), RS1000168682 (5:38853186 A>C), RS1000175351 (5:38934282 A>G), RS1000203057 (5:38934544 C>G,T), RS1000209882 (5:38845654 G>A), RS1000220553 (5:38914443 C>T), RS1000239470 (5:38845849 C>G,T), RS1000245036 (5:38866511 T>A,G), RS1000245741 (5:38846134 C>G,T), RS1000269622 (5:38903152 A>G), RS1000297260 (5:38890922 G>T)

Disease associations

OMIM: gene MIM:601743 | disease phenotypes: MIM:105250

GenCC curated gene-disease

Disease	Classification	Inheritance
amyloidosis, primary localized cutaneous, 1	Strong	Autosomal dominant
familial primary localized cutaneous amyloidosis	Supportive	Autosomal dominant

Mondo (2): amyloidosis, primary localized cutaneous, 1 (MONDO:0024522), familial primary localized cutaneous amyloidosis (MONDO:0007101)

Orphanet (1): Familial primary localized cutaneous amyloidosis (Orphanet:353220)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000958	Dry skin
HP:0000989	Pruritus
HP:0011463	Childhood onset
HP:0012309	Cutaneous amyloidosis
HP:0040189	Scaling skin
HP:0100725	Lichenification

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST001762_699	Obesity-related traits	8.000000e-07
GCST002868_9	Response to serotonin reuptake inhibitors in major depressive disorder	4.000000e-06
GCST003043_72	Inflammatory bowel disease	2.000000e-20
GCST003044_153	Crohn’s disease	2.000000e-16
GCST003045_99	Ulcerative colitis	9.000000e-12
GCST003253_15	Microalbuminuria	8.000000e-06
GCST003518_45	Daytime sleep phenotypes	3.000000e-06
GCST003542_52	Night sleep phenotypes	3.000000e-06
GCST003542_80	Night sleep phenotypes	4.000000e-06
GCST004131_99	Inflammatory bowel disease	5.000000e-10
GCST004132_42	Crohn’s disease	2.000000e-07
GCST004133_41	Ulcerative colitis	4.000000e-06
GCST005537_24	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	8.000000e-15
GCST007650_1	Postoperative survival time in hepatocellular carcinoma	1.000000e-32
GCST007731_5	Postoperative survival time in hepatocellular carcinoma	1.000000e-32
GCST009425_1	Central retinal vein equivalent	7.000000e-07
GCST010083_131	Hemoglobin levels	1.000000e-09
GCST90002383_205	Hematocrit	2.000000e-14
GCST90002384_104	Hemoglobin	3.000000e-14
GCST90002385_270	High light scatter reticulocyte count	8.000000e-12
GCST90002386_17	High light scatter reticulocyte percentage of red cells	2.000000e-14
GCST90002386_18	High light scatter reticulocyte percentage of red cells	9.000000e-15
GCST90002387_103	Immature fraction of reticulocytes	7.000000e-14
GCST90002406_160	Reticulocyte fraction of red cells	8.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007828	daytime rest measurement
EFO:0000638	overall survival
EFO:0010554	retinal vasculature measurement
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562643	amyloidosis IX (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630885 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1239344	OSMR		0.00	0
rs74378198	OSMR		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — IL-6 receptor family

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	4
Aflatoxin B1	affects expression, increases expression	4
Irinotecan	increases expression, decreases response to substance	2
Acetaminophen	decreases expression, increases expression	2
Copper	affects binding, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
ethyl-p-hydroxybenzoate	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	decreases expression	1
doxifluridine	decreases response to substance	1
ciglitazone	affects binding, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
candoxin	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	increases expression	1
Gefitinib	affects response to substance	1
Resveratrol	affects cotreatment, decreases expression	1

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 2 transformed cell line, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1ZK	Abcam HeLa OSMR KO	Cancer cell line	Female
CVCL_B5QN	WAe009-A-82	Embryonic stem cell	Female
CVCL_D7WB	Ubigene A-549 OSMR KO	Cancer cell line	Male
CVCL_D8RU	Ubigene HCT 116 OSMR KO	Cancer cell line	Male
CVCL_D9LX	Ubigene HEK293 OSMR KO	Transformed cell line	Female
CVCL_E0JJ	Ubigene HeLa OSMR KO	Cancer cell line	Female
CVCL_E8EG	HEK-Blue IL-31	Transformed cell line	Female

Clinical trials (associated diseases)

8 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07052214	PHASE3	RECRUITING	PSMA PET Combined With MRI for the Detection of PCa
NCT04680130	Not specified	ENROLLING_BY_INVITATION	Clinico-Pathologic-Genetic-Imaging Study of Neurodegenerative and Related Disorders
NCT04929054	Not specified	UNKNOWN	PCR Based CEUS in BI RADS 4A Nodules
NCT05688371	Not specified	UNKNOWN	Dexmedetomidine Plus Low Dose Morphine Versus Standard Dose of Morphine in PCA in Children .
NCT05845281	Not specified	COMPLETED	Comparison of Erector Spinae Plane Block and Intravenous Patient-controlled Analgesia in Percutaneous Nephrolithotomy
NCT06820190	Not specified	RECRUITING	Analgesic Efficacy of Multiple Mid-Transverse Process to Pleura (MTP) Block and PCA in Idiopathic Scoliosis Patients Undergoing Posterior Spinal Fusion
NCT07051109	Not specified	RECRUITING	Dual-chamber Patient-controlled Analgesia for Postoperative Recovery
NCT01164241	Not specified	COMPLETED	Natural History of Severe Allergic Inflammation and Reactions