IL20RA

Summary

IL20RA (interleukin 20 receptor subunit alpha, HGNC:6003) is a protein-coding gene on chromosome 6q23.3, encoding Interleukin-20 receptor subunit alpha (Q9UHF4). The IL20RA/IL20RB dimer is a receptor for IL19, IL20 and IL24.

This gene encodes a member of the type II cytokine receptor family. The encoded protein is a subunit of the receptor for interleukin 20, a cytokine that may be involved in epidermal function. The interleukin 20 receptor is a heterodimeric complex consisting of the encoded protein and interleukin 20 receptor beta. This gene and interleukin 20 receptor beta are highly expressed in skin, and are upregulated in psoriasis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 53832 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_014432

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6003
Approved symbol	IL20RA
Name	interleukin 20 receptor subunit alpha
Location	6q23.3
Locus type	gene with protein product
Status	Approved
Aliases	ZCYTOR7, IL-20R1
Ensembl gene	ENSG00000016402
Ensembl biotype	protein_coding
OMIM	605620
Entrez	53832

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000316649, ENST00000367746, ENST00000367748, ENST00000460306, ENST00000461799, ENST00000468393, ENST00000541547, ENST00000635289, ENST00000878901, ENST00000878902, ENST00000878903, ENST00000955115, ENST00000955116

RefSeq mRNA: 4 — MANE Select: NM_014432 NM_001278722, NM_001278723, NM_001278724, NM_014432

CCDS: CCDS5181, CCDS64535, CCDS64536

Canonical transcript exons

ENST00000316649 — 7 exons

Exon	Start	End
ENSE00000798902	136999971	137002355
ENSE00001275554	137011274	137011452
ENSE00003538085	137004621	137004760
ENSE00003566025	137009317	137009492
ENSE00003596353	137008599	137008743
ENSE00003615676	137016968	137017103
ENSE00003920991	137044641	137044965

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 92.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4570 / max 33.1182, expressed in 179 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75808	0.2319	119
75809	0.1706	71
75810	0.0439	12
75807	0.0107	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	92.40	gold quality
skin of abdomen	UBERON:0001416	91.30	gold quality
right uterine tube	UBERON:0001302	89.89	gold quality
skin of leg	UBERON:0001511	89.42	gold quality
zone of skin	UBERON:0000014	88.23	gold quality
bronchial epithelial cell	CL:0002328	86.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.85	gold quality
endometrium	UBERON:0001295	83.39	gold quality
upper leg skin	UBERON:0004262	83.21	gold quality
epithelium of bronchus	UBERON:0002031	83.20	gold quality
palpebral conjunctiva	UBERON:0001812	82.52	gold quality
bronchus	UBERON:0002185	82.31	gold quality
upper arm skin	UBERON:0004263	81.61	gold quality
left adrenal gland cortex	UBERON:0035825	81.20	gold quality
minor salivary gland	UBERON:0001830	80.86	gold quality
left adrenal gland	UBERON:0001234	80.78	gold quality
body of pancreas	UBERON:0001150	80.67	gold quality
vagina	UBERON:0000996	80.66	gold quality
right adrenal gland cortex	UBERON:0035827	80.60	gold quality
right adrenal gland	UBERON:0001233	80.37	gold quality
saliva-secreting gland	UBERON:0001044	80.01	gold quality
islet of Langerhans	UBERON:0000006	80.00	gold quality
pancreas	UBERON:0001264	79.67	gold quality
adrenal cortex	UBERON:0001235	79.42	gold quality
parotid gland	UBERON:0001831	79.23	gold quality
choroid plexus epithelium	UBERON:0003911	79.09	gold quality
nasal cavity mucosa	UBERON:0001826	78.94	gold quality
mouth mucosa	UBERON:0003729	78.34	gold quality
mammalian vulva	UBERON:0000997	78.25	gold quality
endocervix	UBERON:0000458	78.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT2

miRNA regulators (miRDB)

77 targeting IL20RA, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-5571-5P	99.49	66.99	1764

Literature-anchored findings (GeneRIF, showing 12)

• forms stable complex with interleukin-19 and interleukin-20 [IL-20R1][IL-20R2] (PMID:14580208)
• sensitivity to recombinant interleukin-26(IL-26) of various cell lines strictly correlated with the expression of IL-20 1 receptor and blocking antibodies against either IL-10 receptor 2 or IL-20 receptor 1 inhibited IL-26-dependent signal transduction (PMID:15178681)
• The hypotheses that genetic variations of the IL-20-RI influence susceptibility to psoriasis was investigated. (PMID:18480827)
• Complete mda-7/IL-24 receptors (IL-22R1/IL-20R2 and IL-20R1/IL-20R2) are seldom expressed in liver cancer cell lines. (PMID:19666410)
• IL-20RA polymorphisms may have a role in psoriasis (PMID:19926456)
• crystallographic asymmetric unit contains one IL-20-IL-20R1-IL-20R2 complex, corresponding to a solvent content of approximately 54% (PMID:22232181)
• IL20R1 correlated with prognosis of patients with pancreatic cancer, and mediates pancreatic cancer cell growth and migration. It may be a potential biomarker for IL24 molecular-targeted therapy. (PMID:26977011)
• the DNA fragment containing the associated SNPs interacts through chromatin looping not only with TNFAIP3, but also with IL20RA, located 680 kb upstream. (PMID:27799070)
• IL-20RA gene as a risk factor for multiple autoimmune diseases. (PMID:29483615)
• Multiple sequence alignment explains the stabilizing effect of the mutated residues in the IL-24 variants by their presence in the related and more stable cytokines IL-20 and IL-19 (PMID:31152679)
• IL20RA signaling enhances stemness and promotes the formation of an immunosuppressive microenvironment in breast cancer. (PMID:33456560)
• MicroRNA 452 regulates IL20RA-mediated JAK1/STAT3 pathway in inflammatory colitis and colorectal cancer. (PMID:34283251)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	il20ra	ENSDARG00000032571
mus_musculus	Il20ra	ENSMUSG00000020007
rattus_norvegicus	Il20ra	ENSRNOG00000012286

Paralogs (11): IFNGR1 (ENSG00000027697), IL10RA (ENSG00000110324), F3 (ENSG00000117525), IFNAR1 (ENSG00000142166), IL22RA1 (ENSG00000142677), IFNAR2 (ENSG00000159110), IFNGR2 (ENSG00000159128), IL22RA2 (ENSG00000164485), IL20RB (ENSG00000174564), IFNLR1 (ENSG00000185436), IL10RB (ENSG00000243646)

Protein

Protein identifiers

Interleukin-20 receptor subunit alpha — Q9UHF4 (reviewed: Q9UHF4)

Alternative names: Cytokine receptor class-II member 8, Cytokine receptor family 2 member 8, IL-20R1, ZcytoR7

All UniProt accessions (5): Q9UHF4, A0A0U1RQS0, A0A0U1RQU9, A0A0U1RRA1, Q96SH7

UniProt curated annotations — full annotation on UniProt →

Function. The IL20RA/IL20RB dimer is a receptor for IL19, IL20 and IL24. The IL20RA/IL10RB dimer is a receptor for IL26.

Subunit / interactions. Heterodimer with IL20RB and heterodimer with IL10RB.

Subcellular location. Membrane.

Tissue specificity. Widely expressed with highest levels in skin and testis and high levels in brain. Highly expressed in psoriatic skin.

Similarity. Belongs to the type II cytokine receptor family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UHF4-1	1	yes
Q9UHF4-2	2
Q9UHF4-3	3

RefSeq proteins (4): NP_001265651, NP_001265652, NP_001265653, NP_055247* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015373	Interferon/interleukin_rcp_dom	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR050650

Pfam: PF01108, PF09294

UniProt features (43 total): strand 13, glycosylation site 6, splice variant 3, helix 3, compositionally biased region 2, disulfide bond 2, topological domain 2, sequence variant 2, turn 2, domain 2, region of interest 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4DOH	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHF4-F1	63.69	0.37

Functional residue map

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

Disulfide bonds (2): 87–95, 215–236

Glycosylation sites (6): 42, 83, 91, 182, 191, 200

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8854691	Interleukin-20 family signaling

MSigDB gene sets: 141 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_DENDRITIC_CELL_DIFFERENTIATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, TTTGTAG_MIR520D, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_NEGATIVE_REGULATION_OF_TYPE_II_INTERFERON_PRODUCTION, GOBP_CYTOKINE_PRODUCTION

GO Biological Process (3): cytokine-mediated signaling pathway (GO:0019221), regulation of bone resorption (GO:0045124), positive regulation of intrinsic apoptotic signaling pathway (GO:2001244)

GO Molecular Function (3): cytokine receptor activity (GO:0004896), interleukin-20 binding (GO:0042015), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Interleukins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytokine binding	2
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
bone resorption	1
regulation of bone remodeling	1
intrinsic apoptotic signaling pathway	1
positive regulation of intracellular signal transduction	1
positive regulation of apoptotic signaling pathway	1
regulation of intrinsic apoptotic signaling pathway	1
transmembrane signaling receptor activity	1
cytokine-mediated signaling pathway	1
immune receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL20RA	IL24	Q13007	997
IL20RA	IL20RB	Q6UXL0	989
IL20RA	IL10RB	Q08334	987
IL20RA	IL19	Q9UHD0	982
IL20RA	IL26	Q9NPH9	980
IL20RA	IL22RA1	Q8N6P7	927
IL20RA	IL22	Q9GZX6	867
IL20RA	IFNL1	Q8IU54	761
IL20RA	IFNL3	Q8IZI9	733
IL20RA	STAT3	P40763	721
IL20RA	IFNL2	Q8IZJ0	677
IL20RA	STAT1	P42224	643
IL20RA	IL10	P22301	642
IL20RA	IL10RA	Q13651	594
IL20RA	CRHR2	Q13324	543

IntAct

11 interactions, top by confidence:

A	B	Type	Score
IL20	IL20RA	psi-mi:“MI:0407”(direct interaction)	0.640
IL20RA	IL20	psi-mi:“MI:0915”(physical association)	0.640
IL20RB	IL20	psi-mi:“MI:0915”(physical association)	0.600
IL20RB	IL19	psi-mi:“MI:0915”(physical association)	0.600
IL20RA	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
IL20RA	IL20RB	psi-mi:“MI:0915”(physical association)	0.520
IL20RA	IL19	psi-mi:“MI:0915”(physical association)	0.400
IL20RA	MLH1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (58): TNIK (Affinity Capture-MS), UBB (Affinity Capture-MS), NFRKB (Affinity Capture-MS), LAPTM4B (Affinity Capture-MS), DIRAS1 (Affinity Capture-MS), STAT3 (Affinity Capture-MS), PIK3CA (Affinity Capture-MS), CYB5R1 (Affinity Capture-MS), CDC6 (Affinity Capture-MS), ROCK1 (Affinity Capture-MS), TAF7 (Affinity Capture-MS), THAP11 (Affinity Capture-MS), C2CD2L (Affinity Capture-MS), ARF5 (Affinity Capture-MS), SNX17 (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: K9JA28, Q3SYS8, Q80XZ4, Q8CGK5, Q8IU57, Q9UHF4, P15260, P15261, Q08334, Q61190, Q764M8, Q6PHB0, Q7TNI4, Q61727, Q80XF5, Q8N6P7, Q969J5, Q04790, Q28589

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
IL19	up-regulates	IL20RA	binding
IL20RA	up-regulates	JAK1	binding
IL26	up-regulates	IL20RA	binding
IL20RA	up-regulates	STAT3

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1231 predictions. Top by Δscore:

Variant	Effect	Δscore
6:137002351:AAAAT:A	acceptor_gain	1.0000
6:137002352:AAAT:A	acceptor_gain	1.0000
6:137002353:AAT:A	acceptor_gain	1.0000
6:137002353:AATC:A	acceptor_loss	1.0000
6:137002354:AT:A	acceptor_gain	1.0000
6:137002355:TC:T	acceptor_loss	1.0000
6:137002356:C:CC	acceptor_gain	1.0000
6:137008593:GCTTA:G	donor_loss	1.0000
6:137008594:CTTAC:C	donor_loss	1.0000
6:137008595:TTA:T	donor_loss	1.0000
6:137008596:TACC:T	donor_loss	1.0000
6:137008597:A:T	donor_loss	1.0000
6:137008741:CCA:C	acceptor_gain	1.0000
6:137008742:CA:C	acceptor_gain	1.0000
6:137008742:CAC:C	acceptor_gain	1.0000
6:137008743:AC:A	acceptor_loss	1.0000
6:137008744:C:CC	acceptor_gain	1.0000
6:137008744:C:T	acceptor_loss	1.0000
6:137009358:T:TA	donor_gain	1.0000
6:137009494:T:C	acceptor_gain	1.0000
6:137009494:T:TC	acceptor_gain	1.0000
6:137011342:A:C	donor_gain	1.0000
6:137016966:A:AC	donor_gain	1.0000
6:137016967:C:CC	donor_gain	1.0000
6:137016977:TG:T	donor_gain	1.0000
6:137017104:C:CC	acceptor_gain	1.0000
6:137004756:TTGAT:T	acceptor_gain	0.9900
6:137004757:TGATC:T	acceptor_loss	0.9900
6:137004758:GATC:G	acceptor_loss	0.9900
6:137004759:ATCT:A	acceptor_loss	0.9900

AlphaMissense

3594 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:137017024:C:A	W56C	0.999
6:137017024:C:G	W56C	0.999
6:137017026:A:G	W56R	0.999
6:137017026:A:T	W56R	0.999
6:137011290:G:C	F129L	0.996
6:137011290:G:T	F129L	0.996
6:137011292:A:G	F129L	0.996
6:137011393:C:G	C95S	0.995
6:137011394:A:T	C95S	0.995
6:137011434:C:A	W81C	0.995
6:137011434:C:G	W81C	0.995
6:137017025:C:G	W56S	0.995
6:137017036:A:C	N52K	0.995
6:137017036:A:T	N52K	0.995
6:137011387:A:G	L97P	0.994
6:137011393:C:T	C95Y	0.994
6:137017045:G:C	N49K	0.994
6:137017045:G:T	N49K	0.994
6:137017052:G:A	S47F	0.994
6:137011291:A:G	F129S	0.993
6:137011348:G:T	A110D	0.993
6:137011355:A:C	Y108D	0.993
6:137011394:A:G	C95R	0.993
6:137011417:C:G	C87S	0.993
6:137011418:A:G	C87R	0.993
6:137011418:A:T	C87S	0.993
6:137011436:A:G	W81R	0.993
6:137011436:A:T	W81R	0.993
6:137017031:A:G	L54P	0.993
6:137011387:A:T	L97H	0.992

dbSNP variants (sampled 300 via entrez): RS1000117513 (6:137033086 C>G,T), RS1000179133 (6:137022205 C>G), RS1000199418 (6:137002404 A>C), RS1000312850 (6:137028870 C>G,T), RS1000416528 (6:137035278 C>T), RS1000505815 (6:137022421 A>G), RS1000591930 (6:137030365 C>T), RS1000624953 (6:137042678 T>C), RS1000646762 (6:137027393 A>G,T), RS1000723026 (6:137034472 C>T), RS1000789117 (6:137035617 C>T), RS1000805898 (6:137040807 A>T), RS1000894904 (6:137035016 A>T), RS1000966853 (6:137010294 G>A), RS1000998527 (6:137024683 G>A)

Disease associations

OMIM: gene MIM:605620 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002352_1	Type 2 diabetes	7.000000e-06
GCST009597_286	Multiple sclerosis	9.000000e-36

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — IL-10 receptor family

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Nickel	decreases expression	2
Progesterone	increases expression, affects cotreatment	2
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenate	decreases expression, increases abundance	1
S 1 (combination)	increases response to substance	1
CGP 52608	affects binding, increases reaction	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects binding, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Dihydrotestosterone	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases 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_E8EE	HEK-Blue IL-19/IL-20	Transformed cell line	Female

Clinical trials (associated diseases)

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