IFNLR1

Summary

IFNLR1 (interferon lambda receptor 1, HGNC:18584) is a protein-coding gene on chromosome 1p36.11, encoding Interferon lambda receptor 1 (Q8IU57). The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity.

The protein encoded by this gene belongs to the class II cytokine receptor family. This protein forms a receptor complex with interleukine 10 receptor, beta (IL10RB). The receptor complex has been shown to interact with three closely related cytokines, including interleukin 28A (IL28A), interleukin 28B (IL28B), and interleukin 29 (IL29). The expression of all three cytokines can be induced by viral infection. The cells overexpressing this protein have been found to have enhanced responses to IL28A and IL29, but decreased response to IL28B. Three alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 163702 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 102 total
• Druggable target: yes
• MANE Select transcript: NM_170743

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18584
Approved symbol	IFNLR1
Name	interferon lambda receptor 1
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	CRF2/12, IFNLR, IL-28R1
Ensembl gene	ENSG00000185436
Ensembl biotype	protein_coding
OMIM	607404
Entrez	163702

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000327535, ENST00000327575, ENST00000374418, ENST00000374419, ENST00000374421, ENST00000873466, ENST00000923176

RefSeq mRNA: 3 — MANE Select: NM_170743 NM_170743, NM_173064, NM_173065

CCDS: CCDS248, CCDS249, CCDS250

Canonical transcript exons

ENST00000327535 — 7 exons

Exon	Start	End
ENSE00001290894	24161542	24161684
ENSE00001308424	24159474	24159633
ENSE00001309701	24159052	24159182
ENSE00001760958	24154168	24157891
ENSE00003493660	24169417	24169601
ENSE00003571153	24180731	24180854
ENSE00003849118	24187191	24187289

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 88.30.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8514 / max 20.3231, expressed in 456 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11036	0.8514	456

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	88.30	gold quality
jejunal mucosa	UBERON:0000399	83.31	gold quality
oviduct epithelium	UBERON:0004804	83.07	gold quality
buccal mucosa cell	CL:0002336	80.92	gold quality
kidney epithelium	UBERON:0004819	79.81	gold quality
right lobe of liver	UBERON:0001114	78.56	gold quality
jejunum	UBERON:0002115	78.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.54	silver quality
mucosa of sigmoid colon	UBERON:0004993	77.53	gold quality
colonic mucosa	UBERON:0000317	77.39	gold quality
cerebellar vermis	UBERON:0004720	76.69	gold quality
duodenum	UBERON:0002114	76.25	gold quality
cardiac muscle of right atrium	UBERON:0003379	76.19	gold quality
cerebellar cortex	UBERON:0002129	76.10	gold quality
cerebellar hemisphere	UBERON:0002245	76.07	gold quality
cerebellum	UBERON:0002037	75.76	gold quality
left ventricle myocardium	UBERON:0006566	75.65	gold quality
liver	UBERON:0002107	75.51	gold quality
lymph node	UBERON:0000029	75.44	gold quality
amniotic fluid	UBERON:0000173	74.72	silver quality
right hemisphere of cerebellum	UBERON:0014890	74.61	gold quality
pituitary gland	UBERON:0000007	74.60	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.56	silver quality
skin of leg	UBERON:0001511	74.04	gold quality
tonsil	UBERON:0002372	74.01	gold quality
body of pancreas	UBERON:0001150	73.94	gold quality
lower esophagus mucosa	UBERON:0035834	73.90	gold quality
pancreas	UBERON:0001264	73.68	gold quality
palpebral conjunctiva	UBERON:0001812	73.54	gold quality
zone of skin	UBERON:0000014	73.42	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IKZF1, STAT1

miRNA regulators (miRDB)

102 targeting IFNLR1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
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-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-302E	99.96	70.74	2669
HSA-LET-7D-5P	99.96	71.76	1632

Literature-anchored findings (GeneRIF, showing 33)

• IL-28 and IL-29 interact with a heterodimeric class II cytokine receptor that consisted of IL-10 receptor beta (IL-10Rbeta) and an orphan class II receptor chain, designated IL-28Ralpha. (PMID:12469119)
• distinct receptor complex that is utilized by all three IFN-lambda proteins for signaling and is composed of two subunits, a receptor designated CRF2-12 (also designated as IFN-lambdaR1) and a second subunit, CRF2-4 (also known as IL-10R2) (PMID:12483210)
• interleukin (IL)-28 receptor tyrosine residues have roles in antiviral and antiproliferative activity of IL-29/interferon-lambda 1 (PMID:15166220)
• Results suggested that the g.32349 G>A polymorphism of IL-28RA might be associated with susceptibility to allergic rhinitis. (PMID:16819289)
• study supports that IFN-lambdas do not influence every type of cell and that membrane-associated variant IFN-lambda R1 expression is not sufficient to ensure cellular sensitivity toward these cytokines. (PMID:19798076)
• Although the IFN-lambda1(Bac)-IFN-lambda1R1 and IFN-lambda1(Ins)-IFN-lambda1R1 complexes differed only in the nature of the expression system used for the ligand, their crystallization conditions and crystal forms were quite different (PMID:20057073)
• IFN-lambdaR1 consists of two distinct domains having fibronectin type III topology. (PMID:20934432)
• two SNPs in IL28RA are correlated with susceptibility to HCV infection and spontaneous viral clearance, which implicates a primary role of IL28RA in the outcomes of HCV infection (PMID:21742059)
• No consistent association is found between IL28RA and multiple sclerosis in a Basque-Spanish population. (PMID:22386267)
• Plasmacytoid dendritic cells are major producers of IFN-lambda2 (a type III interferon) in response to viral stimulation and also express functional receptors for this cytokine. (PMID:22891284)
• The rs12980275 AG/GG genotype and rs10903035 G allele remained independently associated with early pegylated interferon and ribavirin failure of hepatitis C in hepatitis C/HIV coinfected patients. (PMID:23565619)
• Results show that the distribution of IL10RB and IL28RA genotypes among the Hepatitis C virus-infected and control groups did not differ significantly. (PMID:24144988)
• Epigenetic reprogramming of IFNLR1-mediated response potentiates antiviral activity and suppresses tumor growth. (PMID:24409098)
• IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype. (PMID:24438680)
• This study is the first to show the activation of a type III interferon response in low-risk human papillomavirus positive cervical cells and suggests that the lack of this response may be related to lesion progression. (PMID:24510368)
• IFN-lambda receptor 1 expression is induced in chronic hepatitis C and correlates with the IFN-lambda3 genotype and with nonresponsiveness to IFN-alpha therapies. (PMID:24752298)
• expression of IL-28RA mRNA may be correlated with the pathogenesis of systemic lupus erythematosus (PMID:25911176)
• Polymorphism within the IL-28R1, but not in IL-28B, is associated with benign prostatic hyperplasia and lower urinary tract symptoms in Chinese. (PMID:26400298)
• Results show that IFNLR1 box1 and box2 motifs are required for stable complex formation with JAK1 and the crystal structure of JAK1 reveals IFNLR1 box1 binding site in the FERM domain. Also, structure-based mutagenesis reveals IFNLR1 PxxLxF motif that is essential for binding. Structure of JAK1 with IL10RA box1 indicates conservation among class II receptors. (PMID:27133025)
• Selective expression of IFNlambdaR1 was considered to be a plus point towards the targeted anti-viral activity of IFNlambdas but artificial control on its expression will surely make IFNlambdas a better drug with enhanced activity. (PMID:27166550)
• In this structure, the receptor peptide forms an 85-A-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. (PMID:27725180)
• Significant associations were observed for 4 variants in IFNAR2, IFNLR1 with hepatitis B virus infection, and IFNLR1-rs4649203 was associated with hepatitis B recovery. Moreover, the authors demonstrated the clear relevance of 5 polymorphisms in IFNA1, IFNA2, IFNL4 with hepatocellular carcinoma. (PMID:29080269)
• This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism.. IFNLR1 mutations are associated with ADNSHL (PMID:29453195)
• Interferon lambda receptor 1 (IFNLR1) mRNA is increased in human rhinovirus (HRV) bronchiolitis infants. Increased IFNLR1 transcript levels characterized HRV-infected infants with more severe bronchiolitis and blood eosinophilia. IFNLR1 transcript is increased in infants infected with HRVC species. (PMID:29549834)
• IFN-lambda4 suppressed HIV infection of macrophages. This IFN-lambda4-mediated HIV inhibition was compromised by the antibodies against IFN-lambda receptor complex, IFN-lambdaR1/IL-10R2. (PMID:30247785)
• Genetic Polymorphisms of the IFNLR1 Gene Correlate with HCV Infection and Biochemical Features of Chronic HCV Patients in Yunnan, China. (PMID:31366248)
• Significance of IL28RA in diagnosis of early pancreatic cancer and its regulation to pancreatic cancer cells by JAK/STAT signaling pathway - effects of IL28RA on pancreatic cancer. (PMID:31799654)
• Differential expression of interferon-lambda receptor 1 splice variants determines the magnitude of the antiviral response induced by interferon-lambda 3 in human immune cells. (PMID:32353085)
• Interferon III-related IL28RA variant is associated with rheumatoid arthritis and systemic lupus erythematosus and specific disease sub-phenotypes. (PMID:33269531)
• Association of TNFRSF1A and IFNLR1 Gene Polymorphisms with the Risk of Developing Breast Cancer and Clinical Pathologic Features. (PMID:33751344)
• Downregulated expression of IL28RA is involved in the pathogenesis of pancreatic ductal adenocarcinoma. (PMID:34195850)
• Influence of Canonical and Non-Canonical IFNLR1 Isoform Expression on Interferon Lambda Signaling. (PMID:36992341)
• Interferon lambda receptor-1 isoforms differentially influence gene expression and HBV replication in stem cell-derived hepatocytes. (PMID:38070830)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	crfb2	ENSDARG00000040332
mus_musculus	Ifnlr1	ENSMUSG00000062157
rattus_norvegicus	Ifnlr1	ENSRNOG00000033984

Paralogs (11): IL20RA (ENSG00000016402), IFNGR1 (ENSG00000027697), IL10RA (ENSG00000110324), F3 (ENSG00000117525), IFNAR1 (ENSG00000142166), IL22RA1 (ENSG00000142677), IFNAR2 (ENSG00000159110), IFNGR2 (ENSG00000159128), IL22RA2 (ENSG00000164485), IL20RB (ENSG00000174564), IL10RB (ENSG00000243646)

Protein

Protein identifiers

Interferon lambda receptor 1 — Q8IU57 (reviewed: Q8IU57)

Alternative names: Cytokine receptor class-II member 12, Cytokine receptor family 2 member 12, Interleukin-28 receptor subunit alpha, Likely interleukin or cytokine receptor 2

All UniProt accessions (2): Q8IU57, Q5VTX9

UniProt curated annotations — full annotation on UniProt →

Function. The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity. The ligand/receptor complex stimulate the activation of the JAK/STAT signaling pathway leading to the expression of IFN-stimulated genes (ISG), which contribute to the antiviral state. Determines the cell type specificity of the lambda interferon action. Shows a more restricted pattern of expression in the epithelial tissues thereby limiting responses to lambda interferons primarily to epithelial cells of the respiratory, gastrointestinal, and reproductive tracts. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium.

Subunit / interactions. Heterodimer with IL10RB.

Subcellular location. Membrane.

Tissue specificity. Widely expressed.

Post-translational modifications. Ubiquitinated by FBXO45-containing E3 ligase leading to proteasomal degradation.

Similarity. Belongs to the type II cytokine receptor family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8IU57-1	1, IL-28R-alpha-v1	yes
Q8IU57-2	2, IL-28R-alpha-v2
Q8IU57-3	3, IL-28R-alpha-v3
Q8IU57-4	4, Secreted

RefSeq proteins (3): NP_734464, NP_775087, NP_775088 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR050650

Pfam: PF01108

UniProt features (48 total): strand 17, splice variant 5, helix 5, glycosylation site 4, compositionally biased region 3, disulfide bond 3, topological domain 2, mutagenesis site 2, region of interest 2, signal peptide 1, chain 1, transmembrane region 1, turn 1, domain 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
3OG6	X-RAY DIFFRACTION	2.1
5L04	X-RAY DIFFRACTION	2.1
3OG4	X-RAY DIFFRACTION	2.16
5IXI	X-RAY DIFFRACTION	2.57
5T5W	X-RAY DIFFRACTION	2.85
5IXD	X-RAY DIFFRACTION	2.85
9BPV	ELECTRON MICROSCOPY	3
9BPU	ELECTRON MICROSCOPY	3.26

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IU57-F1	64.69	0.33

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 (3): 74–82, 86–150, 195–217

Glycosylation sites (4): 29, 36, 142, 169

Mutagenesis-validated functional residues (2):

Position	Phenotype
319	more resistant to viral-induced degradation; when associated with r-320.
320	more resistant to viral-induced degradation; when associated with r-319.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-449836	Other interleukin signaling
R-HSA-8854691	Interleukin-20 family signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-449147	Signaling by Interleukins

MSigDB gene sets: 106 (showing top): GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DEFENSE_RESPONSE_TO_VIRUS, AACTTT_UNKNOWN, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_REGULATION_OF_DEFENSE_RESPONSE, GOBP_REGULATION_OF_CELLULAR_RESPIRATION

GO Biological Process (9): mucosal immune response (GO:0002385), negative regulation of cell population proliferation (GO:0008285), cytokine-mediated signaling pathway (GO:0019221), response to type III interferon (GO:0034342), type III interferon-mediated signaling pathway (GO:0038196), regulation of defense response to virus by host (GO:0050691), defense response to virus (GO:0051607), cellular response to virus (GO:0098586), positive regulation of cellular respiration (GO:1901857)

GO Molecular Function (2): cytokine receptor activity (GO:0004896), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), interleukin-28 receptor complex (GO:0032002)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by Interleukins	2
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to virus	2
organ or tissue specific immune response	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
response to cytokine	1
innate immune response	1
cellular response to type III interferon	1
interferon-mediated signaling pathway	1
regulation of defense response to virus	1
defense response	1
positive regulation of metabolic process	1
regulation of cellular respiration	1
cellular respiration	1
transmembrane signaling receptor activity	1
cytokine-mediated signaling pathway	1
cytokine binding	1
immune receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1
plasma membrane signaling receptor complex	1

Protein interactions and networks

STRING

1311 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFNLR1	IL10RB	Q08334	999
IFNLR1	IFNL1	Q8IU54	999
IFNLR1	IFNL3	Q8IZI9	999
IFNLR1	IFNL2	Q8IZJ0	999
IFNLR1	IFNAR1	P17181	966
IFNLR1	JAK1	P23458	956
IFNLR1	IL10RA	Q13651	930
IFNLR1	TYK2	P29597	862
IFNLR1	STAT1	P42224	853
IFNLR1	IFNAR2	P48551	828
IFNLR1	IFNA13	P01562	821
IFNLR1	IL26	Q9NPH9	820
IFNLR1	STAT2	P52630	803
IFNLR1	IL10	P22301	798
IFNLR1	IFNB1	P01574	782

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CTXN3	IFNLR1	psi-mi:“MI:0915”(physical association)	0.560
IFNLR1	ANKRD46	psi-mi:“MI:0915”(physical association)	0.560
ANKRD46	IFNLR1	psi-mi:“MI:0915”(physical association)	0.560
PAEP	IFNLR1	psi-mi:“MI:0915”(physical association)	0.560
BRICD5	IFNLR1	psi-mi:“MI:0915”(physical association)	0.560
IFNLR1	JAK1	psi-mi:“MI:0914”(association)	0.530
IFNL1	IFNLR1	psi-mi:“MI:0407”(direct interaction)	0.440
AP2B1	IFNLR1	psi-mi:“MI:0407”(direct interaction)	0.440
IFNLR1	AURKA	psi-mi:“MI:0914”(association)	0.350
PAEP	IFNLR1	psi-mi:“MI:0915”(physical association)	0.000
BRICD5	IFNLR1	psi-mi:“MI:0915”(physical association)	0.000
LSM8	IFNLR1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (50): IFNLR1 (Reconstituted Complex), RANBP9 (Affinity Capture-Western), IFNLR1 (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), IFNLR1 (Two-hybrid), IFNLR1 (Two-hybrid), ANKRD46 (Two-hybrid), CTXN3 (Two-hybrid), ATP2B2 (Affinity Capture-MS), PNPLA6 (Affinity Capture-MS), MR1 (Affinity Capture-MS), TMEM18 (Affinity Capture-MS), AP1G2 (Affinity Capture-MS), SGPL1 (Affinity Capture-MS), GPR50 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, D3YX43, D3YZF7, D7PDD4, O70394, O70540, P01877, P01880, P13599, P14784, P16297, P22272, P22273, P26896, P26952, P40223, P40238, P40321, P70289, P97378, Q15109, Q28173, Q38J84, Q38J85, Q3TYX2, Q5BK54, Q5DID0, Q5NKT8, Q60837, Q61559, Q61790, Q61826, Q62151, Q63495, Q64612, Q6UWB1, Q7TN88, Q7Z442, Q86VR7, Q8IU57

Diamond homologs: K9JA28, Q3SYS8, Q80XZ4, Q8CGK5, Q8IU57, Q9UHF4, V5JFY4

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
IFNLR1	up-regulates	JAK1	binding
IFNLR1	up-regulates	TYK2	binding
IFNL1	up-regulates	IFNLR1	binding
IFNL2	up-regulates	IFNLR1	binding
IFNL3	up-regulates	IFNLR1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	18
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1820 predictions. Top by Δscore:

Variant	Effect	Δscore
1:24161583:T:TA	donor_gain	1.0000
1:24161680:CTCCA:C	acceptor_gain	1.0000
1:24161682:CCA:C	acceptor_gain	1.0000
1:24161683:CA:C	acceptor_gain	1.0000
1:24161683:CAC:C	acceptor_gain	1.0000
1:24161685:C:CC	acceptor_gain	1.0000
1:24169415:A:AT	donor_loss	1.0000
1:24169416:CCTTC:C	donor_loss	1.0000
1:24169602:C:CC	acceptor_gain	1.0000
1:24187185:CCTTA:C	donor_loss	1.0000
1:24187186:CTTA:C	donor_loss	1.0000
1:24187187:TTA:T	donor_loss	1.0000
1:24187188:TACC:T	donor_loss	1.0000
1:24187190:C:CA	donor_loss	1.0000
1:24157639:G:A	donor_gain	0.9900
1:24159105:T:TA	donor_gain	0.9900
1:24159180:CTT:C	acceptor_gain	0.9900
1:24159183:C:CC	acceptor_gain	0.9900
1:24159630:GGGT:G	acceptor_gain	0.9900
1:24159631:GGT:G	acceptor_gain	0.9900
1:24159638:T:TC	acceptor_gain	0.9900
1:24161562:T:TA	donor_gain	0.9900
1:24161580:A:AC	donor_gain	0.9900
1:24161581:C:CC	donor_gain	0.9900
1:24161681:TCCA:T	acceptor_gain	0.9900
1:24161682:CCAC:C	acceptor_gain	0.9900
1:24161682:CCACT:C	acceptor_loss	0.9900
1:24161684:ACT:A	acceptor_loss	0.9900
1:24161686:T:A	acceptor_loss	0.9900
1:24161688:C:CT	acceptor_gain	0.9900

AlphaMissense

3369 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:24180784:C:A	W43C	0.996
1:24180784:C:G	W43C	0.996
1:24180786:A:G	W43R	0.994
1:24180786:A:T	W43R	0.994
1:24169580:C:A	W68C	0.993
1:24169580:C:G	W68C	0.993
1:24169488:C:G	R99P	0.990
1:24169539:C:G	C82S	0.989
1:24169540:A:T	C82S	0.989
1:24159514:G:C	S210R	0.988
1:24159514:G:T	S210R	0.988
1:24159516:T:G	S210R	0.988
1:24180791:A:G	L41P	0.988
1:24159551:G:T	A198D	0.986
1:24159560:C:G	C195S	0.985
1:24159561:A:T	C195S	0.985
1:24180802:G:C	F37L	0.983
1:24180802:G:T	F37L	0.983
1:24180804:A:G	F37L	0.983
1:24161563:C:A	W163C	0.982
1:24161563:C:G	W163C	0.982
1:24161669:G:T	P128H	0.982
1:24169538:A:C	C82W	0.982
1:24169582:A:G	W68R	0.980
1:24169582:A:T	W68R	0.980
1:24169539:C:T	C82Y	0.978
1:24159552:C:G	A198P	0.977
1:24169492:C:G	G98R	0.977
1:24169492:C:T	G98R	0.977
1:24169540:A:G	C82R	0.977

dbSNP variants (sampled 300 via entrez): RS1000073414 (1:24175574 C>T), RS1000080231 (1:24171129 C>T), RS1000400185 (1:24177544 G>A), RS1000502823 (1:24160096 G>A), RS1000533888 (1:24160359 G>A), RS1000843678 (1:24172348 C>T), RS1000976367 (1:24179303 G>A,T), RS1001006925 (1:24166721 T>A), RS1001086835 (1:24172662 C>A,T), RS1001105272 (1:24185059 A>C), RS1001118989 (1:24154641 G>A,C), RS1001180628 (1:24177441 C>T), RS1001235892 (1:24164032 G>A), RS1001256568 (1:24160932 C>T), RS1001318135 (1:24157006 C>T)

Disease associations

OMIM: gene MIM:607404 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000833_12	Psoriasis	7.000000e-08
GCST001201_6	Response to platinum-based chemotherapy (cisplatin)	1.000000e-06
GCST001204_4	Response to platinum-based chemotherapy (carboplatin)	1.000000e-06
GCST002740_66	Inflammatory skin disease	2.000000e-09
GCST002874_21	Psoriasis	1.000000e-06
GCST002937_13	Molybdenum levels	6.000000e-06
GCST003268_34	Psoriasis vulgaris	3.000000e-11
GCST005537_147	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	1.000000e-08
GCST006585_2	Blood protein levels	3.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3831284 (PROTEIN COMPLEX)

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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	3
Tetrachlorodibenzodioxin	increases expression	3
(+)-JQ1 compound	decreases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
TL8-506	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	increases expression, affects cotreatment	1
entinostat	increases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
gardiquimod	increases expression, decreases reaction	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	affects expression	1
Doxorubicin	affects expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Phenobarbital	affects expression	1
Poly I-C	affects cotreatment, increases expression	1
Testosterone	decreases expression	1
Urethane	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1ZZ	HAP1 IFNLR1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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