IL27RA

Summary

IL27RA (interleukin 27 receptor subunit alpha, HGNC:17290) is a protein-coding gene on chromosome 19p13.12, encoding Interleukin-27 receptor subunit alpha (Q6UWB1). Receptor for IL27.

In mice, CD4+ helper T-cells differentiate into type 1 (Th1) cells, which are critical for cell-mediated immunity, predominantly under the influence of IL12. Also, IL4 influences their differentiation into type 2 (Th2) cells, which are critical for most antibody responses. Mice deficient in these cytokines, their receptors, or associated transcription factors have impaired, but are not absent of, Th1 or Th2 immune responses. This gene encodes a protein which is similar to the mouse T-cell cytokine receptor Tccr at the amino acid level, and is predicted to be a glycosylated transmembrane protein.

Source: NCBI Gene 9466 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Epstein-Barr virus infection (Moderate, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 122 total — 3 pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_004843

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17290
Approved symbol	IL27RA
Name	interleukin 27 receptor subunit alpha
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	WSX-1, TCCR, CRL1, WSX1, zcytor1, IL-27R
Ensembl gene	ENSG00000104998
Ensembl biotype	protein_coding
OMIM	605350
Entrez	9466

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000263379, ENST00000855328, ENST00000855329, ENST00000855330, ENST00000917020, ENST00000917021, ENST00000963616, ENST00000963617

RefSeq mRNA: 1 — MANE Select: NM_004843 NM_004843

CCDS: CCDS12303

Canonical transcript exons

ENST00000263379 — 14 exons

Exon	Start	End
ENSE00000685382	14042453	14042612
ENSE00000685385	14042716	14042789
ENSE00000685387	14046154	14046337
ENSE00000685389	14046430	14046618
ENSE00000685394	14049156	14049314
ENSE00000685396	14050758	14050883
ENSE00000685399	14051607	14051700
ENSE00000685403	14051880	14051973
ENSE00000836540	14032386	14032503
ENSE00000836541	14039508	14039665
ENSE00000836542	14039753	14039910
ENSE00000951071	14048981	14049082
ENSE00001126468	14031762	14031972
ENSE00001232348	14052096	14053218

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 93.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6989 / max 153.0557, expressed in 1580 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174209	9.7991	1563
174208	0.4431	216
174210	0.3029	93
174211	0.1539	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.71	gold quality
leukocyte	CL:0000738	91.27	gold quality
monocyte	CL:0000576	91.03	gold quality
lymph node	UBERON:0000029	88.53	gold quality
blood	UBERON:0000178	87.08	gold quality
vermiform appendix	UBERON:0001154	85.68	gold quality
spleen	UBERON:0002106	81.67	gold quality
apex of heart	UBERON:0002098	79.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.50	gold quality
bone marrow cell	CL:0002092	77.38	gold quality
upper lobe of left lung	UBERON:0008952	77.13	gold quality
omental fat pad	UBERON:0010414	76.47	gold quality
bone marrow	UBERON:0002371	75.65	gold quality
lung	UBERON:0002048	75.63	gold quality
heart left ventricle	UBERON:0002084	75.49	gold quality
tonsil	UBERON:0002372	75.12	gold quality
right lung	UBERON:0002167	74.60	gold quality
adipose tissue	UBERON:0001013	74.54	gold quality
lower esophagus mucosa	UBERON:0035834	74.51	gold quality
thoracic mammary gland	UBERON:0005200	74.21	gold quality
gall bladder	UBERON:0002110	73.74	gold quality
duodenum	UBERON:0002114	73.13	gold quality
cortical plate	UBERON:0005343	72.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.83	gold quality
heart	UBERON:0000948	72.83	gold quality
subcutaneous adipose tissue	UBERON:0002190	72.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.79	gold quality
smooth muscle tissue	UBERON:0001135	72.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.49	gold quality
placenta	UBERON:0001987	72.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting IL27RA, 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-8068	99.98	73.85	2376
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-3130-5P	98.14	66.00	711
HSA-MIR-615-5P	98.10	63.76	591

Literature-anchored findings (GeneRIF, showing 19)

• WSX-1 is essential for transcriptional activation of STAT1 and for augmenting the induction of T-bet expression during initiation of Th1 cell differentiation. (PMID:12734330)
• WSX-1 together with the cytokine receptor gp130 constitutes a functional signal-transducing receptor for IL-27. (PMID:14764690)
• IL-27R possesses hematopoietic cell-transforming properties (PMID:18003935)
• These results indicate that humanin protects neurons by binding to a complex or complexes involving CNTFR/WSX-1/gp130. (PMID:19386761)
• Results reveal an interleukin 27-independent function of WSX1 sensitizing natural killer cell-mediated antitumor surveillance. (PMID:19549909)
• Mutations in the transmembrane and juxtamembrane domains enhance IL27R transforming activity. (PMID:21631431)
• TCCR/WSX-1 is closely associated with angiogenesis and could serve as a novel therapeutic target in patients with age-related macular degeneration. (PMID:22312192)
• Aberrant hypermethylation and reduced expression of IL27RA is associated with myelodysplastic syndromes. (PMID:22936014)
• natural sIL-27Ralpha binds rIL-27, inhibits IL-27 binding to its cell surface receptor, and is a potent inhibitor of IL-27 signaling, as shown by its ability to specifically block IL-27-mediated STAT activation, at low molar excess over IL-27. (PMID:24771852)
• The significant expression of IL-27 in TB and the negative influence of IL-27R on T cell function demonstrate the pathway by which this cytokine/receptor pair is detrimental in TB. (PMID:26282876)
• Findings demonstrated that IL-27 and IL-27R were elevated in multiple sclerosis lesions and that local IL-27 can modulate immune properties of astrocytes and infiltrating immune cells (PMID:26649511)
• These results identify IL-27 and its specific receptor IL27RA as a critical immune axis for the antiviral immune response and as robust correlates of viral load and proviral reservoir size in mononuclear leukocytes in HIV infection. (PMID:28592538)
• this study found elevated expression of IL-27 in human peripheral serum and elevated expression of its specific receptor (wsx-1) on fetal membranes in cases of preterm birth (PMID:28756371)
• Loss of IL-27Ralpha Results in Enhanced Tubulointerstitial Fibrosis Associated with Elevated Th17 Responses. (PMID:32522836)
• WSX1 act as a tumor suppressor in hepatocellular carcinoma by downregulating neoplastic PD-L1 expression. (PMID:34108491)
• IL27 Signaling Serves as an Immunologic Checkpoint for Innate Cytotoxic Cells to Promote Hepatocellular Carcinoma. (PMID:35723626)
• Structural insights into the assembly and activation of the IL-27 signaling complex. (PMID:35920255)
• Cytokine receptor IL27RA is an NF-kappaB-responsive gene involved in CD38 upregulation in multiple myeloma. (PMID:36867577)
• Role of IL-27 in Epstein-Barr virus infection revealed by IL-27RA deficiency. (PMID:38509369)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	ghrb	ENSDARG00000007671
danio_rerio	il11ra	ENSDARG00000026736
danio_rerio	lifrb	ENSDARG00000039863
danio_rerio	il2rgb	ENSDARG00000053702
danio_rerio	ghra	ENSDARG00000054771
danio_rerio	il2rga	ENSDARG00000068858
danio_rerio	crlf2	ENSDARG00000090632
danio_rerio	lifra	ENSDARG00000098857
danio_rerio	il6r	ENSDARG00000104474
mus_musculus	Il27ra	ENSMUSG00000005465
rattus_norvegicus	Il27ra	ENSRNOG00000005747

Paralogs (23): CRLF1 (ENSG00000006016), IL12RB2 (ENSG00000081985), IL5RA (ENSG00000091181), IL12RB1 (ENSG00000096996), 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), IL31RA (ENSG00000164509), IL3RA (ENSG00000185291), CSF2RA (ENSG00000198223), CRLF2 (ENSG00000205755)

Protein

Protein identifiers

Interleukin-27 receptor subunit alpha — Q6UWB1 (reviewed: Q6UWB1)

Alternative names: Cytokine receptor WSX-1, Cytokine receptor-like 1, Type I T-cell cytokine receptor, ZcytoR1

All UniProt accessions (1): Q6UWB1

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for IL27. Requires IL6ST/GP130 to mediate signal transduction in response to IL27. This signaling system acts through STAT3 and STAT1. Acts as a receptor for the neuroprotective peptide humanin as part of a complex with IL6ST/GP130 and CNTFR. Involved in the regulation of Th1-type immune responses. Also appears to be involved in innate defense mechanisms.

Subunit / interactions. Component of a receptor complex composed of IL6ST/GP130, IL27RA/WSX1 and CNTFR which interacts with the neuroprotective peptide humanin.

Subcellular location. Membrane.

Tissue specificity. Highly expressed in lymphoid tissues such as spleen, lymph nodes and peripheral blood leukocytes. Weakly expressed in other tissues examined including heart, brain, fetal and adult lung, liver, skeletal muscle, kidney, pancreas, prostate, testis, ovary, small intestine, kidney and colon. In the lymphoid system, higher level expression in CD4+ T-cell subsets than in CD8+ T-cell subsets. Also weaker expression in CD19+ B-cells and monocytes.

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.

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

RefSeq proteins (1): NP_004834* (*=MANE)

Domains & families (InterPro)

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

UniProt features (40 total): strand 17, glycosylation site 7, domain 3, short sequence motif 2, topological domain 2, helix 2, signal peptide 1, chain 1, compositionally biased region 1, sequence conflict 1, turn 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7T5M	X-RAY DIFFRACTION	1.67
7U7N	ELECTRON MICROSCOPY	3.47
8D85	ELECTRON MICROSCOPY	3.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWB1-F1	78.99	0.41

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 (7): 51, 76, 302, 311, 374, 382, 467

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8984722	Interleukin-35 Signalling
R-HSA-9020956	Interleukin-27 signaling

MSigDB gene sets: 354 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, MODULE_45, MODULE_64, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_B_CELL_PROLIFERATION

GO Biological Process (15): positive regulation of T-helper 1 type immune response (GO:0002827), negative regulation of type 2 immune response (GO:0002829), immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), negative regulation of interleukin-17 production (GO:0032700), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of type II interferon production (GO:0032729), negative regulation of neuron apoptotic process (GO:0043524), regulation of isotype switching to IgG isotypes (GO:0048302), defense response to Gram-positive bacterium (GO:0050830), negative regulation of T-helper 17 type immune response (GO:2000317), negative regulation of T cell extravasation (GO:2000408), negative regulation of cellular extravasation (GO:0002692), interleukin-27-mediated signaling pathway (GO:0070106)

GO Molecular Function (3): transmembrane signaling receptor activity (GO:0004888), interleukin-27 receptor activity (GO:0045509), 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
Interleukin-12 family signaling	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cytokine production	2
positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
regulation of T-helper 1 type immune response	1
T-helper 1 type immune response	1
regulation of type 2 immune response	1
type 2 immune response	1
negative regulation of immune response	1
immune system process	1
response to stimulus	1
signal transduction	1
interleukin-17 production	1
regulation of interleukin-17 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
regulation of isotype switching	1
isotype switching to IgG isotypes	1
defense response to bacterium	1
negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
T-helper 17 type immune response	1
regulation of T-helper 17 type immune response	1
negative regulation of cellular extravasation	1
T cell extravasation	1
negative regulation of T cell migration	1
regulation of T cell extravasation	1
negative regulation of leukocyte migration	1
regulation of cellular extravasation	1
cellular extravasation	1
cytokine-mediated signaling pathway	1
signaling receptor activity	1
interleukin-17 receptor activity	1
interleukin-27 binding	1

Protein interactions and networks

STRING

967 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL27RA	CNTFR	P26992	995
IL27RA	IL6ST	P40189	986
IL27RA	IL27	Q8NEV9	982
IL27RA	IL12RB2	Q99665	978
IL27RA	IL12RB1	P42701	960
IL27RA	IL6R	P08887	889
IL27RA	CNTF	P26441	880
IL27RA	IL6	P05231	844
IL27RA	STAT1	P42224	800
IL27RA	TBX21	Q9UL17	792
IL27RA	JAK2	O60674	777
IL27RA	STAT3	P40763	752
IL27RA	CD4	P01730	731
IL27RA	EBI3	Q14213	727
IL27RA	JAK1	P23458	720

IntAct

47 interactions, top by confidence:

A	B	Type	Score
IL27RA	IL6ST	psi-mi:“MI:0914”(association)	0.590
IL27RA	IL6ST	psi-mi:“MI:0915”(physical association)	0.590
GALNT15	IL27RA	psi-mi:“MI:0915”(physical association)	0.560
IL27RA	MFSD5	psi-mi:“MI:0915”(physical association)	0.560
MFSD5	IL27RA	psi-mi:“MI:0915”(physical association)	0.560
BRICD5	IL27RA	psi-mi:“MI:0915”(physical association)	0.560
DEFB121	IL27RA	psi-mi:“MI:0915”(physical association)	0.560
IL27RA	YIPF6	psi-mi:“MI:0915”(physical association)	0.560
IL27RA	GALNT15	psi-mi:“MI:0915”(physical association)	0.560
IL27RA	DERL3	psi-mi:“MI:0915”(physical association)	0.560
CLDN2	IL27RA	psi-mi:“MI:0915”(physical association)	0.560
IL27RA	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
IL27RA	B4GALT5	psi-mi:“MI:0914”(association)	0.530
IL27RA	AP1G2	psi-mi:“MI:0914”(association)	0.530
rep	IL27RA	psi-mi:“MI:0915”(physical association)	0.490
IL27RA	NRP1	psi-mi:“MI:0914”(association)	0.350
SRPRA	ANXA13	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DRB3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SCN3B	A2ML1	psi-mi:“MI:0914”(association)	0.350
TNFSF18	FAM171A2	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	FAAH	psi-mi:“MI:0914”(association)	0.350

BioGRID (86): IL27RA (Affinity Capture-Western), IL27 (Affinity Capture-Western), EBI3 (Affinity Capture-Western), POTEE (Affinity Capture-MS), TMX4 (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), FNDC3A (Affinity Capture-MS), IL27RA (Affinity Capture-MS), DEPDC1 (Affinity Capture-MS), ULBP3 (Affinity Capture-MS), B4GALT5 (Affinity Capture-MS), RHBDD3 (Affinity Capture-MS), PLD6 (Affinity Capture-MS), AP1G2 (Affinity Capture-MS), LENG8 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A6H8M9, A7LCJ3, A8E0Y8, D3YX43, D3YZF7, O14498, O15197, O70394, O70540, P01877, P0C0K6, P0C788, P0DP72, P35590, P40223, P43121, P50895, P70289, Q00657, Q06418, Q06805, Q15109, Q28173, Q5BK54, Q5NVQ6, Q5TJE4, Q61790, Q61826, Q62151, Q62230, Q63495, Q64612, Q6UVK1, Q6UWB1, Q7Z442, Q86VR7, Q8IZF5, Q8R2Y2, Q8VHY0

Diamond homologs: O70394, Q6UWB1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IL27	up-regulates	IL27RA	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	87
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
4526901	IL27RA, GLN96TER (rs375317876)	Pathogenic
4526902	IL27RA, ARG446GLY (rs201107107)	Pathogenic
4526903	IL27RA, IVS8, A-C, -2 (rs778365769)	Pathogenic

SpliceAI

1516 predictions. Top by Δscore:

Variant	Effect	Δscore
19:14031971:GG:G	donor_gain	1.0000
19:14031972:GG:G	donor_gain	1.0000
19:14032043:GA:G	donor_gain	1.0000
19:14032499:AAGTA:A	donor_gain	1.0000
19:14032501:GTA:G	donor_gain	1.0000
19:14032502:TA:T	donor_gain	1.0000
19:14032504:G:GG	donor_gain	1.0000
19:14039608:GGCAC:G	donor_gain	1.0000
19:14039609:GCAC:G	donor_gain	1.0000
19:14039666:G:GG	donor_gain	1.0000
19:14039751:A:AG	acceptor_gain	1.0000
19:14039752:G:GA	acceptor_gain	1.0000
19:14039752:GT:G	acceptor_gain	1.0000
19:14039910:GGTG:G	donor_loss	1.0000
19:14039911:G:A	donor_loss	1.0000
19:14039911:G:GG	donor_gain	1.0000
19:14039912:T:A	donor_loss	1.0000
19:14042450:CA:C	acceptor_loss	1.0000
19:14042451:A:AG	acceptor_gain	1.0000
19:14042451:A:C	acceptor_loss	1.0000
19:14042451:AGCT:A	acceptor_gain	1.0000
19:14042451:AGCTG:A	acceptor_gain	1.0000
19:14042452:G:GA	acceptor_gain	1.0000
19:14042452:GCT:G	acceptor_gain	1.0000
19:14042452:GCTG:G	acceptor_gain	1.0000
19:14042452:GCTGG:G	acceptor_gain	1.0000
19:14046426:CCA:C	acceptor_loss	1.0000
19:14046427:CA:C	acceptor_loss	1.0000
19:14046428:A:AG	acceptor_gain	1.0000
19:14046429:G:GG	acceptor_gain	1.0000

AlphaMissense

4056 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:14049223:G:C	W437C	0.982
19:14049223:G:T	W437C	0.982
19:14049067:T:C	F410L	0.979
19:14049069:C:A	F410L	0.979
19:14049069:C:G	F410L	0.979
19:14046500:G:C	W341C	0.976
19:14046500:G:T	W341C	0.976
19:14049221:T:A	W437R	0.976
19:14049221:T:C	W437R	0.976
19:14032447:G:C	W54C	0.972
19:14032447:G:T	W54C	0.972
19:14052228:T:C	F617L	0.968
19:14052230:C:A	F617L	0.968
19:14052230:C:G	F617L	0.968
19:14032439:T:A	C52S	0.967
19:14032440:G:C	C52S	0.967
19:14046498:T:A	W341R	0.967
19:14046498:T:C	W341R	0.967
19:14039603:T:A	V105D	0.961
19:14039827:T:A	W151R	0.960
19:14039827:T:C	W151R	0.960
19:14042579:A:C	S221R	0.960
19:14042581:C:A	S221R	0.960
19:14042581:C:G	S221R	0.960
19:14046578:G:C	W367C	0.960
19:14046578:G:T	W367C	0.960
19:14039873:T:C	F166S	0.958
19:14042732:G:C	W237C	0.957
19:14042732:G:T	W237C	0.957
19:14049216:T:A	I435K	0.957

dbSNP variants (sampled 300 via entrez): RS1000194760 (19:14030522 C>G,T), RS1000542564 (19:14041727 A>AC), RS1000781116 (19:14033364 T>G), RS1000949044 (19:14053090 A>G), RS1001409588 (19:14032832 G>A,T), RS1001509509 (19:14032302 T>C), RS1001543645 (19:14032902 C>A), RS1001609508 (19:14038925 G>A), RS1001719499 (19:14031341 T>A), RS1001755388 (19:14044895 G>A,C), RS1001850284 (19:14044583 A>G), RS1002120847 (19:14036638 A>G), RS1002145265 (19:14038660 G>A), RS1002364497 (19:14051774 G>C,T), RS1002534362 (19:14041976 G>A)

Disease associations

OMIM: gene MIM:605350 | disease phenotypes: MIM:621405

GenCC curated gene-disease

Disease	Classification	Inheritance
Epstein-Barr virus infection	Moderate	Autosomal recessive

Mondo (2): immunodeficiency 134 (Epstein-Barr virus-specific) (MONDO:0980729), Epstein-Barr virus infection (MONDO:0005111)

Orphanet (0):

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001399	Hepatic failure
HP:0001433	Hepatosplenomegaly
HP:0001639	Hypertrophic cardiomyopathy
HP:0001888	Decreased total lymphocyte count
HP:0001903	Anemia
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002788	Recurrent upper respiratory tract infections
HP:0003593	Infantile onset
HP:0005404	Increased total B cell count
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0011873	Abnormal platelet count
HP:0011950	Bronchiolitis
HP:0012115	Hepatitis
HP:0020072	Persistent EBV viremia
HP:0025435	Increased circulating lactate dehydrogenase concentration
HP:0025624	Decreased CD4+ effector memory T cell proportion
HP:0030374	Decreased proportion of memory B cells
HP:0030948	Elevated gamma-glutamyltransferase level
HP:0031691	Severe viral infection
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0031964	Elevated circulating alanine aminotransferase concentration
HP:0033050	Pharyngalgia
HP:0033479	Abnormal circulating bilirubin concentration
HP:0100827	Increased total lymphocyte count
HP:0410295	Complete or near-complete absence of specific antibody response to tetanus vaccine
HP:0410390	Decreased effector memory CD8+ T cell proportion
HP:6001425	Hyperleukocytosis

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002441_4	Immune response to measles-mumps-rubella vaccine	3.000000e-07
GCST006585_2066	Blood protein levels	9.000000e-39
GCST90002388_41	Lymphocyte count	2.000000e-13
GCST90002389_393	Lymphocyte percentage of white cells	3.000000e-12
GCST90002399_224	Neutrophil percentage of white cells	1.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020031	Epstein-Barr Virus Infections	C01.925.256.466.313; C01.925.928.313

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-6 receptor family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
epigallocatechin gallate	decreases expression, affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression, affects methylation, decreases methylation	2
Cisplatin	affects expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cupric chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetylcysteine	decreases expression	1
Air Pollutants	increases abundance, increases expression	1

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7S5	Ubigene A-549 IL27RA KO	Cancer cell line	Male
CVCL_D8N6	Ubigene HCT 116 IL27RA KO	Cancer cell line	Male
CVCL_D9H3	Ubigene HEK293 IL27RA KO	Transformed cell line	Female
CVCL_E0F2	Ubigene HeLa IL27RA KO	Cancer cell line	Female
CVCL_E6U7	Genomeditech HEK-293 H_IL27 Reporter	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04183738	PHASE4	WITHDRAWN	Inflammation and Co-Infections in D²EFT
NCT04308278	PHASE4	RECRUITING	Study to Evaluate the Efficacy of 2LEBV® and 2LXFS® on Asthenia in Patients With an Epstein-Barr Virus Infection
NCT04989491	PHASE4	RECRUITING	Evaluation of the Efficacy of a Treatment by One Single Dose of Rituximab (375mg/m2 ) in the Prevention of the Epstein Barr Virus (EBV) Primary Infection and Post-transplant Lymphoproliferative Disorder in Adult EBV Seronegative Patients Who Received an EBV Seropositive Kidney Allograft
NCT05039580	PHASE4	UNKNOWN	Programmed Cell Death Protein-1 (PD-1) Monoclonal Antibody for EBV-HLH and CAEBV as First-line Therapy
NCT04084626	PHASE3	UNKNOWN	PD1 Antibody and Lenalidomide as a Treatment for EBV-HLH or CAEBV
NCT04832607	PHASE3	RECRUITING	Multivirus-specific T-cell Transfer Post SCT vs AdV, CMV and EBV Infections
NCT00430534	PHASE2	COMPLETED	Evaluation of Safety, Immune-Response and Efficacy of GSK Biologicals’ EBV (Epstein Barr Virus) Vaccine (268664).
NCT01058239	PHASE2	COMPLETED	Bortezomib Plus Rituximab for EBV+ PTLD
NCT01094405	PHASE2	COMPLETED	Efficacy of Recombinant Epstein-Barr Virus (EBV) Vaccine in Patients With Nasopharyngeal Cancer Who Had Residual EBV DNA Load After Conventional Therapy
NCT01972035	PHASE2	COMPLETED	ValGanciclovir Versus ValAcyclovir for Viral Prophylaxis in Kidney Transplantation
NCT03258567	PHASE2	RECRUITING	Nivolumab in Epstein-Barr Virus (EBV)-Positive Lymphoproliferative Disorders and EBV-Positive Non-HodgkinLymphomas
NCT03266653	PHASE2	RECRUITING	EBV-specific Cytotoxic T-lymphocytes (CTLs) for Refractory EBV Infection
NCT07261215	PHASE2	NOT_YET_RECRUITING	Zuberitamab for EBV Infection Post-Allo-HSCT
NCT07368153	PHASE2	NOT_YET_RECRUITING	Safety and Tolerability of IDO-1 Inhibition in the Prevention of EBV-related Pathology in EBV Negative Kidney Transplant Recipients Receiving an Organ From EBV Positive Donors
NCT00058591	PHASE1	COMPLETED	Treating Severe Chronic Epstein-Barr Virus (EBV) Infection With EBV Specific Cytotoxic T Lymphocytes (CTLs)
NCT00058604	PHASE1	COMPLETED	Prevention and Treatment of Epstein-Barr Virus (EBV) Lymphoma Following a Solid Organ Transplant Using EBV Specific Cytotoxic T Lymphocytes (CTLs).
NCT00058812	PHASE1	COMPLETED	Giving Epstein-Barr Virus (EBV) Specific Killer T Lymphocytes to Patients Who Have Had Donor Marrow Grafts
NCT00078546	PHASE1	COMPLETED	EBV-Specific CTLs Following CD45 Antibody to Patients With Epstein-Barr Virus (EBV) + Nasopharyngeal Carcinoma (NPC)
NCT01070797	PHASE1	COMPLETED	Administration of Rapidly Generated Multivirus-specific Cytotoxic T-Lymphocytes (VIRAGE)
NCT01256853	PHASE1	COMPLETED	Modified Vaccinia Ankara (MVA) Vaccine Study
NCT01494103	PHASE1	ACTIVE_NOT_RECRUITING	Administration of Donor T Cells With the Caspase-9 Suicide Gene
NCT01535885	PHASE1	COMPLETED	Using Multi-virus Cytotoxic T-cells Following T-Cell Depleted Allogeneic HPCT for Prophylaxis Against EBV, ADV, and CMV
NCT01800071	PHASE1	COMPLETED	A Phase Ib Trial of MVA-EBNA1/LMP2 Vaccine in Nasopharyngeal Carcinoma
NCT04645147	PHASE1	ACTIVE_NOT_RECRUITING	Safety and Immunogenicity of an Epstein-Barr Virus (EBV) gp350-Ferritin Nanoparticle Vaccine in Healthy Adults With or Without EBV Infection
NCT05183490	PHASE1	RECRUITING	R-MVST Cells for Treatment of Viral Infections
NCT05831111	PHASE1	ACTIVE_NOT_RECRUITING	A Study of an Epstein-Barr Virus (EBV) Candidate Vaccine, mRNA-1195, in 18- to 55-Year-Old Healthy Participants
NCT06135922	PHASE1	RECRUITING	Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection
NCT06789159	PHASE1	RECRUITING	A Phase Ib Study of VK-2019 in Patients With Relapsed or Refractory EBV+ Diffuse Large B-cell Lymphomas (DLBCL)
NCT06908096	PHASE1	RECRUITING	Epstein-Barr Virus (EBV) gH/gL/gp42-Ferritin Nanoparticle Vaccine With or Without gp350-Ferritin in Healthy Adults With or Without EBV Infection
NCT07614282	PHASE1	NOT_YET_RECRUITING	Rituximab for PTLD Prevention in Solid Organ Transplant Recipients With EBV DNAemia
NCT02135042	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Individualized Treatment Treating Patients With Stage II-IVB Nasopharyngeal Cancer Based on EBV DNA
NCT04693637	PHASE2/PHASE3	COMPLETED	Posoleucel (ALVR105, Formerly Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant
NCT05305040	PHASE2/PHASE3	TERMINATED	Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus Prevention in Patients Post-Allogeneic Hematopoietic Cell Transplant
NCT00711035	PHASE1/PHASE2	COMPLETED	Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL)
NCT01805037	PHASE1/PHASE2	TERMINATED	Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas
NCT02580539	PHASE1/PHASE2	COMPLETED	A Study of the Safety and Efficacy of EBV Specific T-cell Lines
NCT03159364	PHASE1/PHASE2	UNKNOWN	Antigen-specific Cytotoxic T Cells in the Treatment of Opportunistic Infections
NCT03475212	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation
NCT03769467	PHASE1/PHASE2	TERMINATED	Tabelecleucel in Combination With Pembrolizumab in Subjects With Epstein-Barr Virus-associated Nasopharyngeal Carcinoma (EBV+ NPC)
NCT04507477	PHASE1/PHASE2	UNKNOWN	Ex-vivo Delivery of Rituximab to Prevent PTLD in EBV Mismatch Lung Transplant Recipients: A Pilot Trial