IL31RA (interleukin 31 receptor A)

Gene

• Entrez ID: 133396
• Gene name: Interleukin 31 receptor A
• Gene symbol: IL31RA
• Synonyms (NCBI Gene): CRL, CRL3, GLM-R, GLMR, GPL, IL-31RA, PLCA2, PRO21384, hGLM-R, zcytoR17
• Chromosome: 5
• Chromosome location: 5q11.2
• 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1561123748	C>T	Pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019063	hsa-miR-335-5p	Microarray	18185580
MIRT1550119	hsa-miR-4660	CLIP-seq
MIRT1550120	hsa-miR-885-3p	CLIP-seq
MIRT1550119	hsa-miR-4660	CLIP-seq
MIRT1550120	hsa-miR-885-3p	CLIP-seq
MIRT1550119	hsa-miR-4660	CLIP-seq
MIRT1550120	hsa-miR-885-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	NAS	11877449
GO:0002067	Process	Glandular epithelial cell differentiation	IEA
GO:0002376	Process	Immune system process	IEA
GO:0002438	Process	Acute inflammatory response to antigenic stimulus	IEA
GO:0003713	Function	Transcription coactivator activity	NAS	11877449
GO:0004896	Function	Cytokine receptor activity	IBA
GO:0004896	Function	Cytokine receptor activity	TAS	11877449
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006952	Process	Defense response	NAS	11877449
GO:0007169	Process	Cell surface receptor protein tyrosine kinase signaling pathway	NAS	11877449
GO:0007259	Process	Cell surface receptor signaling pathway via JAK-STAT	IEP	11877449
GO:0008284	Process	Positive regulation of cell population proliferation	IBA
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	11877449
GO:0009897	Component	External side of plasma membrane	IBA
GO:0009897	Component	External side of plasma membrane	IEA
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	NAS	11877449
GO:0019221	Process	Cytokine-mediated signaling pathway	IBA
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS	11877449
GO:0019901	Function	Protein kinase binding	NAS	11877449
GO:0019955	Function	Cytokine binding	IBA
GO:0019955	Function	Cytokine binding	IEA
GO:0019955	Function	Cytokine binding	NAS	11877449
GO:0030154	Process	Cell differentiation	IEA
GO:0030224	Process	Monocyte differentiation	IEP	11877449
GO:0030225	Process	Macrophage differentiation	NAS	11877449
GO:0030424	Component	Axon	IEA
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	IEP	11877449
GO:0042592	Process	Homeostatic process	NAS	11877449
GO:0042734	Component	Presynaptic membrane	IEA
GO:0042995	Component	Cell projection	IEA
GO:0043031	Process	Negative regulation of macrophage activation	NAS	11877449
GO:0043066	Process	Negative regulation of apoptotic process	NAS	11877449
GO:0043235	Component	Receptor complex	IBA
GO:0045202	Component	Synapse	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	NAS	11877449
GO:0097696	Process	Cell surface receptor signaling pathway via STAT	IEA
GO:0098542	Process	Defense response to other organism	IEA

Other IDs

• MIM: 609510
• HGNC: 18969
• e!Ensembl: ENSG00000164509

Protein

• UniProt ID: Q8NI17
• Protein name: Interleukin-31 receptor subunit alpha (IL-31 receptor subunit alpha) (IL-31R subunit alpha) (IL-31R-alpha) (IL-31RA) (Cytokine receptor-like 3) (GLM-R) (hGLM-R) (Gp130-like monocyte receptor) (Gp130-like receptor) (ZcytoR17)
• Protein 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:15194700, PubMed:15627637). May function in skin immunity (PubMed:15184896). Mediates
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF09240	IL6Ra-bind	27 → 119	Interleukin-6 receptor alpha chain, binding	Domain
  PF00041	fn3	123 → 215	Fibronectin type III domain	Domain
  PF00041	fn3	425 → 507	Fibronectin type III domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in CD14- and CD56-positive blood cells (PubMed:11877449). Expressed in macrophages (PubMed:16461143, PubMed:18439099). Expressed in keratinocytes (PubMed:21261663). Expressed in a subset of dorsal root ganglia neurons (at pro
• Sequence:

  MMWTWALWMLPSLCKFSLAALPAKPENISCVYYYRKNLTCTWSPGKETSYTQYTVKRTYA
  FGEKHDNCTTNSSTSENRASCSFFLPRITIPDNYTIEVEAENGDGVIKSHMTYWRLENIA
  KTEPPKIFRVKPVLGIKRMIQIEWIKPELAPVSSDLKYTLRFRTVNSTSWMEVNFAKNRK
  DKNQTYNLTGLQPFTEYVIALRCAVKESKFWSDWSQEKMGMTEEEAPCGLELWRVLKPAE
  ADGRRPVRLLWKKARGAPVLEKTLGYNIWYYPESNTNLTETMNTTNQQLELHLGGESFWV
  SMISYNSLGKSPVATLRIPAIQEKSFQCIEVMQACVAEDQLVVKWQSSALDVNTWMIEWF
  PDVDSEPTTLSWESVSQATNWTIQQDKLKPFWCYNISVYPMLHDKVGEPYSIQAYAKEGV
  PSEGPETKVENIGVKTVTITWKEIPKSERKGIICNYTIFYQAEGGKGFSKTVNSSILQYG
  LESLKRKTSYIVQVMASTSAGGTNGTSINFKTLSFSVFEIILITSLIGGGLLILIILTVA
  YGLKKPNKLTHLCWPTVPNPAESSIATWHGDDFKDKLNLKESDDSVNTEDRILKPCSTPS
  DKLVIDKLVVNFGNVLQEIFTDEARTGQENNLGGEKNGYVTCPFRPDCPLGKSFEELPVS
  PEIPPRKSQYLRSRMPEGTRPEAKEQLLFSGQSLVPDHLCEEGAPNPYLKNSVTAREFLV
  SEKLPEHTKGEV

• Sequence length: 732

Pathways

KEGG:

Cytokine-cytokine receptor interaction
JAK-STAT signaling pathway

Reactome:

IL-6-type cytokine receptor ligand interactions

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Amyloidosis, primary localized cutaneous, 2	Pathogenic	rs1561123748	RCV000023775	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AMYLOIDOSIS, PRIMARY CUTANEOUS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BRAIN INJURIES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IL31RA-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	29482503		★☆☆☆☆ Found in Text Mining only
Adult Diffuse Large B-Cell Lymphoma	B-cell Lymphoma	BEFREE	31776466		★☆☆☆☆ Found in Text Mining only
Adult type dermatomyositis	Dermatomyositis	BEFREE	29494763		★☆☆☆☆ Found in Text Mining only
Allergic rhinitis (disorder)	Allergic rhinitis	BEFREE	23392388		★☆☆☆☆ Found in Text Mining only
Amyloidosis Primary Cutaneous	Amyloidosis	Pubtator	19690585	Associate	★☆☆☆☆ Found in Text Mining only
Amyloidosis, Primary Cutaneous	Amyloidosis	BEFREE	19690585, 22062952, 26356818, 30734345		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Amyloidosis, Primary Cutaneous	Amyloidosis	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Amyloidosis, Primary Cutaneous	Amyloidosis	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AMYLOIDOSIS, PRIMARY LOCALIZED CUTANEOUS, 1	Amyloidosis	ORPHANET_DG	19690585		★☆☆☆☆ Found in Text Mining only
AMYLOIDOSIS, PRIMARY LOCALIZED CUTANEOUS, 2	Amyloidosis	UNIPROT_DG	19690585		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
AMYLOIDOSIS, PRIMARY LOCALIZED CUTANEOUS, 2	Amyloidosis	GENOMICS_ENGLAND_DG	19690585		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Asthma	Asthma	Pubtator	26956917, 35606283	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	36685508	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	28383684		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	30054229		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	29262645		★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic Fibrosis	BEFREE	19828687		★☆☆☆☆ Found in Text Mining only
Dermatitis, Atopic	Dermatitis	BEFREE	16461143, 24373353, 27714851, 28249150, 29524262, 31434203		★☆☆☆☆ Found in Text Mining only
Dermatomyositis	Dermatomyositis	BEFREE	29494763		★☆☆☆☆ Found in Text Mining only
Dermatomyositis	Dermatomyositis	Pubtator	29494763	Associate	★☆☆☆☆ Found in Text Mining only
Diffuse Large B-Cell Lymphoma	Diffuse Lymphoma	BEFREE	31776466		★☆☆☆☆ Found in Text Mining only
Eczema	Eczema	BEFREE	16461143, 24373353, 27714851, 28249150, 29524262, 31434203		★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	38108937	Associate	★☆☆☆☆ Found in Text Mining only
Ewings sarcoma	Ewing sarcoma	BEFREE	30481065		★☆☆☆☆ Found in Text Mining only
Familial lichen amyloidosis	Lichen amyloidosis	BEFREE	19690585		★☆☆☆☆ Found in Text Mining only
Familial lichen amyloidosis	Lichen amyloidosis	ORPHANET_DG	19690585		★☆☆☆☆ Found in Text Mining only
Familial medullary thyroid carcinoma	Medullary thyroid carcinoma	BEFREE	26356818		★☆☆☆☆ Found in Text Mining only
Familial primary localized cutaneous amyloidosis	Localized Cutaneous Amyloidosis	Orphanet			★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	29990333		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	8145003		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	8145003		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	31476910		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	31680842		★☆☆☆☆ Found in Text Mining only
Lymphangioma, Cystic	Cystic hygroma	BEFREE	12001183		★☆☆☆☆ Found in Text Mining only
Lymphoma, Follicular	Lymphoma	BEFREE	25283844		★☆☆☆☆ Found in Text Mining only
Lymphoma, T-Cell, Cutaneous	Lymphoma	BEFREE	24373353		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	28383684		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	22221038		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	23912815, 28147314, 30481065		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	23912815		★☆☆☆☆ Found in Text Mining only
Miscarriage	Miscarriage	BEFREE	29175064		★☆☆☆☆ Found in Text Mining only
Multiple Endocrine Neoplasia Type 2a	Multiple Endocrine Neoplasia	BEFREE	29420094		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29128526		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	21436895, 23222812	Associate	★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	23222812		★☆☆☆☆ Found in Text Mining only
Osteogenesis Imperfecta	Osteogenesis imperfecta	Pubtator	2981843	Associate	★☆☆☆☆ Found in Text Mining only
Osteogenesis imperfecta, dominant perinatal lethal	Osteogenesis Imperfecta	BEFREE	3857621		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	3470599		★☆☆☆☆ Found in Text Mining only
Pruritus	Pruritus	Pubtator	22041865, 27001482	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	22221038		★☆☆☆☆ Found in Text Mining only
Thrombophilia, hereditary	Thrombophilia	BEFREE	19447935		★☆☆☆☆ Found in Text Mining only
Ventricular Fibrillation, Paroxysmal Familial, 1	Ventricular Fibrillation	BEFREE	29175064		★☆☆☆☆ Found in Text Mining only