IL31RA

Summary

IL31RA (interleukin 31 receptor A, HGNC:18969) is a protein-coding gene on chromosome 5q11.2, encoding Interleukin-31 receptor subunit alpha (Q8NI17). Associates with OSMR to form the interleukin-31 receptor which activates STAT3 and to a lower extent STAT1 and STAT5.

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.

Source: NCBI Gene 133396 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial primary localized cutaneous amyloidosis (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 136 total — 1 pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes
• MANE Select transcript: NM_139017

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18969
Approved symbol	IL31RA
Name	interleukin 31 receptor A
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	CRL3, GLM-R, CRL, Glmr, IL-31RA
Ensembl gene	ENSG00000164509
Ensembl biotype	protein_coding
OMIM	609510
Entrez	133396

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000297015, ENST00000354961, ENST00000359040, ENST00000396834, ENST00000396836, ENST00000490985, ENST00000651239, ENST00000651309, ENST00000651605, ENST00000652039, ENST00000652347, ENST00000652528

RefSeq mRNA: 6 — MANE Select: NM_139017 NM_001242636, NM_001242637, NM_001242638, NM_001242639, NM_001297570, NM_139017

CCDS: CCDS3970, CCDS56365, CCDS56366, CCDS56367, CCDS75244, CCDS75245

Canonical transcript exons

ENST00000652347 — 15 exons

Exon	Start	End
ENSE00001084994	55907359	55907460
ENSE00001084996	55899916	55900132
ENSE00001085000	55906106	55906288
ENSE00001126882	55910532	55910672
ENSE00001158085	55908265	55908411
ENSE00001158122	55896350	55896429
ENSE00001158131	55889970	55890135
ENSE00001158143	55883044	55883195
ENSE00001236276	55914847	55914928
ENSE00001236285	55913477	55913570
ENSE00003603405	55868791	55868908
ENSE00003627332	55872270	55872451
ENSE00003660709	55859509	55859599
ENSE00003848665	55851357	55851633
ENSE00003922096	55916644	55922850

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 78.71.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5656 / max 134.5088, expressed in 323 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56473	0.7755	219
56477	0.3234	43
56478	0.1951	44
56475	0.0872	26
56474	0.0767	42
56476	0.0737	18
56479	0.0340	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.20	gold quality
monocyte	CL:0000576	71.48	gold quality
leukocyte	CL:0000738	71.02	gold quality
thoracic aorta	UBERON:0001515	67.56	gold quality
ascending aorta	UBERON:0001496	67.40	gold quality
dorsal root ganglion	UBERON:0000044	67.06	gold quality
descending thoracic aorta	UBERON:0002345	66.50	gold quality
secondary oocyte	CL:0000655	64.34	gold quality
granulocyte	CL:0000094	64.16	gold quality
pancreatic ductal cell	CL:0002079	62.80	silver quality
trigeminal ganglion	UBERON:0001675	61.14	gold quality
bone marrow cell	CL:0002092	60.90	gold quality
tibia	UBERON:0000979	60.78	silver quality
tendon of biceps brachii	UBERON:0008188	60.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	58.69	gold quality
gingival epithelium	UBERON:0001949	57.39	gold quality
cartilage tissue	UBERON:0002418	57.36	silver quality
aorta	UBERON:0000947	57.06	gold quality
cardiac muscle of right atrium	UBERON:0003379	56.40	gold quality
zone of skin	UBERON:0000014	56.32	gold quality
skin of leg	UBERON:0001511	56.24	gold quality
superficial temporal artery	UBERON:0001614	56.08	gold quality
thymus	UBERON:0002370	55.58	silver quality
skin of abdomen	UBERON:0001416	55.18	gold quality
epithelial cell of pancreas	CL:0000083	54.99	gold quality
nasal cavity epithelium	UBERON:0005384	54.51	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
bone marrow	UBERON:0002371	54.21	gold quality
sural nerve	UBERON:0015488	54.10	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting IL31RA, 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-1207-5P	99.49	69.11	2983
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-5088-3P	98.29	66.63	1310

Literature-anchored findings (GeneRIF, showing 16)

• A novel type I cytokine receptor is expressed on monocytes, signals proliferation, and activates STAT-3 and STAT-5. (PMID:11877449)
• GPL is a novel cytokine receptor related to GP130 and leukemia inhibitory factor receptor (PMID:14504285)
• the molecular mechanisms underlying GPL-mediated signal transduction (PMID:15194700)
• IL-31 receptor alpha expression in epidermal keratinocytes is modulated by cell differentiation and interferon gamma (PMID:18580959)
• ). Binding of IL-31 to its receptor activates Jak/STAT, PI3K/AKT and MAPK pathways.[review] (PMID:18926762)
• 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)
• IFN-gamma-induced IL-31RA upregulation in dermal microvascular endothelium is processed via JNK and PI3 kinase activation (PMID:20849534)
• IL-31 and IL-31RA are upregulated in patients with allergic rhinitis, and induce MUC5AC gene expression in human airway epithelial cells. (PMID:23392388)
• IL31RA is a functional receptor expressed by a small subpopulation of IL-31RA(+)/TRPV1(+)/TRPA1(+) neurons and is a critical neuroimmune link between TH2 cells and sensory nerves for the generation of T cell-mediated itch. (PMID:24373353)
• detected in keratinocytes and nerve fibers in the dermis of atopic dermatitis and in the neurons of normal dorsal root ganglia (PMID:24667097)
• The interleukin IL-31/IL-31receptor axis contributes to tumor growth in human follicular lymphoma. (PMID:25283844)
• The first demonstration of the involvement of the IL-31/IL-31R axis in cancer came from studies in patients with mycosis fungoides/Sezary syndrome, the most frequent, cutaneous T cell lymphoma. Tumor cells were shown to produce IL-31, whose serum levels correlated with pruritus intensity. (PMID:28408397)
• Feline Interleukin-31 Shares Overlapping Epitopes with the Oncostatin M Receptor and IL-31RA. (PMID:32459958)
• Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis. (PMID:34642338)
• IL-31 and IL-31 receptor alpha in pemphigus: Contributors to more than just itch? (PMID:36651089)
• Interleukin 31 receptor alpha promotes smooth muscle cell contraction and airway hyperresponsiveness in asthma. (PMID:38081868)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il31ra	ENSMUSG00000050377
rattus_norvegicus	Il31ra	ENSRNOG00000042080

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), OSMR (ENSG00000145623), IL2RG (ENSG00000147168), IL6R (ENSG00000160712), IL23R (ENSG00000162594), IL3RA (ENSG00000185291), CSF2RA (ENSG00000198223), CRLF2 (ENSG00000205755)

Protein

Protein identifiers

Interleukin-31 receptor subunit alpha — Q8NI17 (reviewed: Q8NI17)

Alternative names: Cytokine receptor-like 3, GLM-R, Gp130-like monocyte receptor, ZcytoR17

All UniProt accessions (4): Q8NI17, A0A494BZY2, A0A494C190, A0A499FJ31

UniProt curated annotations — full annotation on UniProt →

Function. Associates with OSMR to form the interleukin-31 receptor which activates STAT3 and to a lower extent STAT1 and STAT5. May function in skin immunity. Mediates IL31-induced itch, probably in a manner dependent on cation channels TRPA1 and TRPV1. 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.

Subunit / interactions. Heterodimer with OSMR. Interacts with JAK1 and STAT3.

Subcellular location. Cell membrane. Presynaptic cell membrane. Cell projection. Axon.

Tissue specificity. Expressed in CD14- and CD56-positive blood cells. Expressed in macrophages. Expressed in keratinocytes. Expressed in a subset of dorsal root ganglia neurons (at protein level). Expressed at low levels in testis, ovary, brain, prostate, placenta, thymus, bone marrow, trachea and skin. Expressed in bronchial and alveolar epithelial cells and pulmonary fibroblasts. Detected in all of the myelomonocytic lineage. Isoform 6: Expressed at higher levels in lesional skin compared to healthy skin of atopic dermatitis patients.

Post-translational modifications. N-glycosylated.

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

Induction. Up-regulated in lesional keratinocytes of patients with atopic dermatitis. Up-regulated by IFNG/IFN-gamma. Up-regulated by bacterial lipopolysaccharides (LPS). Up-regulated by triacylated lipoprotein (Pam3Cys). Up-regulated by TGFB1/TGF-beta.

Miscellaneous. Major isoform. Dominant negative IL31 receptor. Major isoform. Functional IL31 receptor.

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

Isoforms (12)

UniProt ID	Names	Canonical?
Q8NI17-1	1	yes
Q8NI17-2	2, v3
Q8NI17-3	3, v4
Q8NI17-4	4, v2
Q8NI17-5	5, v1
Q8NI17-6	6
Q8NI17-7	7
Q8NI17-8	8
Q8NI17-9	9, GPL560, short
Q8NI17-10	10, GPL610
Q8NI17-11	11, GPL626
Q8NI17-12	12, GPL745, long

RefSeq proteins (6): NP_001229565, NP_001229566, NP_001229567, NP_001229568, NP_001284499, NP_620586* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015321	TypeI_recpt_CBD	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR052672	Type1_Cytokine_Rcpt_Type2	Family

Pfam: PF00041, PF09240

UniProt features (45 total): splice variant 16, glycosylation site 10, mutagenesis site 6, domain 5, sequence variant 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9EZA	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NI17-F1	74.34	0.44

Functional residue map

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

Glycosylation sites (10): 37, 67, 93, 166, 187, 277, 283, 395, 455, 504

Mutagenesis-validated functional residues (6):

Position	Phenotype
639	no effect on stat1 and stat3 activation. slight decrease; when associated with a-670 and a-708.
639	abrogates stat5 activation. mild effect on stat1 activation. no effect on stat3 activation.
670	no effect on stat1 and stat3 activation. slight decrease; when associated with a-639 and a-708.
670	no effect on stat3 and stat5 activation. mild effect on stat1 activation.
708	no effect on stat1 and stat3 activation. slight decrease; when associated with a-639 and a-670.
708	abrogates stat3 activation. loss of interaction with stat3. mild effect on stat1 activation. no effect on stat5 activati

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 164 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION, GOCC_CELL_SURFACE, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_POSITIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_MYELOID_LEUKOCYTE_ACTIVATION

GO Biological Process (19): MAPK cascade (GO:0000165), glandular epithelial cell differentiation (GO:0002067), acute inflammatory response to antigenic stimulus (GO:0002438), defense response (GO:0006952), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), positive regulation of cell population proliferation (GO:0008284), cytokine-mediated signaling pathway (GO:0019221), monocyte differentiation (GO:0030224), macrophage differentiation (GO:0030225), positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531), homeostatic process (GO:0042592), negative regulation of macrophage activation (GO:0043031), negative regulation of apoptotic process (GO:0043066), positive regulation of DNA-templated transcription (GO:0045893), defense response to other organism (GO:0098542), immune system process (GO:0002376), cell differentiation (GO:0030154), cell surface receptor signaling pathway via STAT (GO:0097696)

GO Molecular Function (5): transcription coactivator activity (GO:0003713), cytokine receptor activity (GO:0004896), protein kinase binding (GO:0019901), cytokine binding (GO:0019955), protein binding (GO:0005515)

GO Cellular Component (8): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), axon (GO:0030424), presynaptic membrane (GO:0042734), signaling receptor complex (GO:0043235), cell projection (GO:0042995), synapse (GO:0045202)

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
cell surface receptor signaling pathway	2
myeloid leukocyte differentiation	2
mononuclear cell differentiation	2
biological_process	2
cellular anatomical structure	2
intracellular signaling cassette	1
columnar/cuboidal epithelial cell differentiation	1
inflammatory response to antigenic stimulus	1
acute inflammatory response	1
response to stress	1
enzyme-linked receptor protein signaling pathway	1
cell surface receptor signaling pathway via STAT	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cellular response to cytokine stimulus	1
tyrosine phosphorylation of STAT protein	1
regulation of tyrosine phosphorylation of STAT protein	1
positive regulation of peptidyl-tyrosine phosphorylation	1
negative regulation of leukocyte activation	1
macrophage activation	1
regulation of macrophage activation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
defense response	1
response to other organism	1
cellular developmental process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
transmembrane signaling receptor activity	1
cytokine-mediated signaling pathway	1
cytokine binding	1
immune receptor activity	1
kinase binding	1
protein binding	1
binding	1

Protein interactions and networks

STRING

2737 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL31RA	IL31	Q6EBC2	999
IL31RA	OSMR	Q99650	989
IL31RA	OSM	P13725	928
IL31RA	DDX4	Q9NQI0	722
IL31RA	JAK1	P23458	697
IL31RA	HSD17B12	Q53GQ0	621
IL31RA	LMO1	P25800	582
IL31RA	JAK2	O60674	542
IL31RA	TRPA1	O75762	536
IL31RA	DUSP12	Q9UNI6	530
IL31RA	CRLF2	Q9HC73	522
IL31RA	RETNLB	Q9BQ08	520
IL31RA	RETN	Q9HD89	519
IL31RA	MRGPRD	Q8TDS7	498
IL31RA	TRPV1	Q8NER1	491

IntAct

5 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TXNL4A	IL31RA	psi-mi:“MI:0915”(physical association)	0.370
IL31RA	DUSP14	psi-mi:“MI:0914”(association)	0.350
IL31RA	BAG6	psi-mi:“MI:0914”(association)	0.350

BioGRID (47): FAM26D (Affinity Capture-MS), LYG2 (Affinity Capture-MS), AIM1 (Affinity Capture-MS), HEPHL1 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), DUSP14 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PADI3 (Affinity Capture-MS), S100A3 (Affinity Capture-MS), SELENBP1 (Affinity Capture-MS), NEU2 (Affinity Capture-MS), PKP3 (Affinity Capture-MS)

ESM2 similar proteins: K7NA32, K7NAJ3, O09030, O70458, O70535, P14753, P16310, P17181, P19235, P21183, P22272, P22273, P24055, P26955, P31785, P33896, P34902, P40190, P40223, P40321, P42701, P42702, P42703, P78552, Q00560, Q04790, Q07303, Q28589, Q5XNR9, Q60837, Q65Z14, Q6PHB0, Q6UXL0, Q764M8, Q7TNI4, Q80XF5, Q8K5B1, Q8MJS1, Q8NI17, Q95118

Diamond homologs: Q8K5B1, Q8NI17

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
IL31	up-regulates	IL31RA	binding
IL31RA	up-regulates	JAK1	binding
IL31RA	up-regulates	JAK2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	91
Likely benign	19
Benign	13

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
30790	NM_139017.7(IL31RA):c.1562C>T (p.Ser521Phe)	Pathogenic

SpliceAI

3202 predictions. Top by Δscore:

Variant	Effect	Δscore
5:55872266:AAAGC:A	acceptor_gain	1.0000
5:55872267:A:G	acceptor_gain	1.0000
5:55872448:ATAGG:A	donor_loss	1.0000
5:55872449:TAGG:T	donor_loss	1.0000
5:55872450:AGGT:A	donor_loss	1.0000
5:55872451:GGT:G	donor_loss	1.0000
5:55872452:G:C	donor_loss	1.0000
5:55872453:T:A	donor_loss	1.0000
5:55883191:GCTGG:G	donor_gain	1.0000
5:55883192:CTGGG:C	donor_loss	1.0000
5:55883194:GG:G	donor_gain	1.0000
5:55883194:GGGT:G	donor_loss	1.0000
5:55883195:GG:G	donor_gain	1.0000
5:55883195:GGTAA:G	donor_loss	1.0000
5:55883196:G:GA	donor_loss	1.0000
5:55883196:G:GG	donor_gain	1.0000
5:55883197:TAAGT:T	donor_loss	1.0000
5:55883858:G:T	donor_gain	1.0000
5:55890129:G:GT	donor_gain	1.0000
5:55899907:T:TA	acceptor_gain	1.0000
5:55907492:G:GT	donor_gain	1.0000
5:55907493:A:T	donor_gain	1.0000
5:55908263:A:AG	acceptor_gain	1.0000
5:55908264:G:GA	acceptor_gain	1.0000
5:55908264:GTTCC:G	acceptor_gain	1.0000
5:55908344:GA:G	donor_gain	1.0000
5:55908412:G:GG	donor_gain	1.0000
5:55910530:A:AG	acceptor_gain	1.0000
5:55910531:G:GG	acceptor_gain	1.0000
5:55910673:G:GG	donor_gain	1.0000

AlphaMissense

5028 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000001735 (5:55840409 C>T), RS1000018698 (5:55887394 A>G), RS1000026036 (5:55894295 G>A), RS1000100039 (5:55851862 C>G,T), RS1000161949 (5:55913621 G>A), RS1000193134 (5:55890379 T>G), RS1000277033 (5:55913898 T>A), RS1000324417 (5:55873278 A>G), RS1000448988 (5:55872855 A>G), RS1000478054 (5:55890618 C>T), RS1000480306 (5:55919009 T>C), RS1000593274 (5:55849350 C>T), RS1000603278 (5:55843142 A>G), RS1000607833 (5:55915301 A>G), RS1000626688 (5:55895927 G>T)

Disease associations

OMIM: gene MIM:609510 | disease phenotypes: MIM:613955

GenCC curated gene-disease

Disease	Classification	Inheritance
familial primary localized cutaneous amyloidosis	Supportive	Autosomal dominant
amyloidosis, primary localized cutaneous, 2	Limited	Autosomal dominant

Mondo (2): amyloidosis, primary localized cutaneous, 2 (MONDO:0013502), familial primary localized cutaneous amyloidosis (MONDO:0007101)

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

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000989	Pruritus
HP:0012309	Cutaneous amyloidosis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001729_4	Crohn’s disease	4.000000e-12

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): CHEMBL4630894 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — IL-6 receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
nemolizumab	Binding	8.7	pKd

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	2
Smoke	increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
bisphenol F	decreases methylation	1
Asian ginseng	affects cotreatment, decreases expression	1
bisphenol A	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	increases expression	1
Cadmium	decreases expression, increases abundance	1
Diethylhexyl Phthalate	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Oxygen	decreases expression	1
Tretinoin	increases expression	1
Vanadates	increases expression	1
Cyclosporine	increases expression	1
Fluorescein-5-isothiocyanate	affects binding	1
Asbestos, Crocidolite	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E8EG	HEK-Blue IL-31	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01164241	Not specified	COMPLETED	Natural History of Severe Allergic Inflammation and Reactions