EBI3

Summary

EBI3 (Epstein-Barr virus induced 3, HGNC:3129) is a protein-coding gene on chromosome 19p13.3, encoding Interleukin-27 subunit beta (Q14213). Associates with IL27 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity.

This gene was identified by its induced expression in B lymphocytes in response Epstein-Barr virus infection. It encodes a secreted glycoprotein belonging to the hematopoietin receptor family, and heterodimerizes with a 28 kDa protein to form interleukin 27 (IL-27). IL-27 regulates T cell and inflammatory responses, in part by activating the Jak/STAT pathway of CD4+ T cells.

Source: NCBI Gene 10148 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_005755

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3129
Approved symbol	EBI3
Name	Epstein-Barr virus induced 3
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	IL27B, IL35B
Ensembl gene	ENSG00000105246
Ensembl biotype	protein_coding
OMIM	605816
Entrez	10148

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000221847, ENST00000599339, ENST00000905122, ENST00000925715

RefSeq mRNA: 1 — MANE Select: NM_005755 NM_005755

CCDS: CCDS12123

Canonical transcript exons

ENST00000221847 — 5 exons

Exon	Start	End
ENSE00000664053	4231191	4231323
ENSE00000664054	4233129	4233307
ENSE00000664055	4234667	4234824
ENSE00000868776	4229523	4229617
ENSE00001115419	4236936	4237528

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 96.81.

FANTOM5 (CAGE): breadth broad, TPM avg 33.0616 / max 3365.5893, expressed in 914 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173302	31.8821	907
173303	0.6980	126
173304	0.3834	108
173307	0.0669	31
173309	0.0225	7
173308	0.0088	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	96.81	gold quality
decidua	UBERON:0002450	92.48	gold quality
spleen	UBERON:0002106	88.84	gold quality
buccal mucosa cell	CL:0002336	81.32	gold quality
vermiform appendix	UBERON:0001154	80.35	gold quality
lymph node	UBERON:0000029	80.06	gold quality
caecum	UBERON:0001153	76.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.91	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.16	gold quality
gall bladder	UBERON:0002110	74.97	gold quality
cervix squamous epithelium	UBERON:0006922	74.54	gold quality
right adrenal gland	UBERON:0001233	74.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.92	gold quality
right coronary artery	UBERON:0001625	73.89	gold quality
right adrenal gland cortex	UBERON:0035827	73.70	gold quality
left adrenal gland	UBERON:0001234	72.96	gold quality
left adrenal gland cortex	UBERON:0035825	72.86	gold quality
spinal cord	UBERON:0002240	72.10	gold quality
adrenal cortex	UBERON:0001235	71.94	gold quality
small intestine	UBERON:0002108	71.84	gold quality
descending thoracic aorta	UBERON:0002345	71.84	gold quality
thoracic aorta	UBERON:0001515	71.20	gold quality
left uterine tube	UBERON:0001303	71.17	gold quality
omental fat pad	UBERON:0010414	71.01	gold quality
peritoneum	UBERON:0002358	70.98	gold quality
ascending aorta	UBERON:0001496	70.66	gold quality
adipose tissue of abdominal region	UBERON:0007808	70.43	gold quality
left coronary artery	UBERON:0001626	70.10	gold quality
adrenal gland	UBERON:0002369	69.91	gold quality
tibial nerve	UBERON:0001323	69.73	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	1899.33
E-MTAB-6678	yes	1612.57
E-MTAB-8498	yes	9.21
E-ANND-3	yes	8.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB1, NFKBIA, RELA, SPI1

miRNA regulators (miRDB)

30 targeting EBI3, 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-4775	99.98	75.00	6394
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-1285-5P	98.01	68.71	779
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-4508	90.37	59.62	240
HSA-MIR-1538	85.86	60.08	75
HSA-MIR-6784-5P	84.56	60.91	126
HSA-MIR-4745-3P	83.50	60.58	126

Literature-anchored findings (GeneRIF, showing 40)

• a new heterodimeric cytokine that consists of EBI3, an IL-12p40-related protein, and p28, a newly discovered IL-12p35-related polypeptide (IL-27) (PMID:12121660)
• results suggest that increased numbers of Epstein-Barr virus-infected cells in areas of active inflammatory bowel disease are secondary to influx or local proliferation of inflammatory cells & do not contribute significantly to local production of EBI3 (PMID:15170639)
• findings indicate that the restricted Th1 responses in newborns owing to deficient IL-12 production may be compensated for, in part, by enhanced IL-27 secretion (PMID:18167155)
• The genome-wide mRNA expression profile under the condition of short-term stimulation (4h) with IL-18 using the Affymetrix GeneChip((R)) Array System, was characterized. (PMID:18336908)
• Our data support a possible role of Ebi3 in atherogenesis (PMID:19556516)
• This study demonstrated that interleukin-35 expression could be detected in the CD4(+) T cells from peripheral blood of chronic hepatitis B patients. (PMID:21285006)
• Data show that Epstein-Barr virus-induced gene 3 (EBI3) is differentially expressed among Burkitt lymphoma and diffuse large B-cell lymphoma. (PMID:21931777)
• IL-27 expression is one host immune factor produced in response to influenza A virus infection and that elevated IL-27 levels inhibit viral replication. (PMID:22343630)
• in contrast to TGF-beta, IL-35 is not constitutively expressed in tissues but it is inducible in response to inflammatory stimuli (PMID:22438968)
• The findings of this study support the potential role of regulatory T cells and genetic variations in the regions around FOXP3 and EBI3 genes in modifying the risk for AR development in Chinese patients. (PMID:22836044)
• these results reveal a novel functional role for IL-35 in suppressing cancer activity, inhibiting cancer cell growth, and increasing the apoptosis sensitivity of human cancer cells through the regulation of genes related to the cell cycle and apoptosis. (PMID:23154182)
• The findings of this study suggest that SNPs in FOXP3 and EBI3 genes modify the risk for development of chronic rhinosinusitis. (PMID:23562195)
• expressed by trophoblast cells (PMID:23619469)
• EBI3-overexpression in MRL/lpr mice induces generation of regulatory T cells, causing suppression of autoimmune and inflammatory reactions by affecting the T helper (Th)1 cell/Th2 cytokine balance. (PMID:23845089)
• the findings from the past decade identify IL-27 as a critical immunoregulatory cytokine, especially for T cells, whereas some controversy is fueled by results challenging the view of IL-27 as a classical silencer of inflammation. (PMID:23904441)
• circulating IL-35 in PDAC patients significantly increased, suggesting that regulating the expression of IL-35 may provide a new possible target for the treatment of PDAC patients, especially for the resectable ones. (PMID:24121041)
• The increased expression of IL-35 in chronic and aggressive periodontitis suggests its possible role in pathogenesis of periodontitis. (PMID:24376289)
• Interleukin-35 induces regulatory B cells that suppress autoimmune disease. [il-35] (PMID:24743305)
• ingestion of apoptotic cells by DCs leads to increased expression of IL-12p35 and Ebi3 without affecting IL-12p40. (PMID:24782489)
• The results suggest that the decreased expression of IL-35 could be involved in the pathogenesis of childhood asthma. (PMID:24970690)
• IL-35 levels are dramatically decreased in immune thrombocytopenia patients, suggesting that IL-35 may be involved in the pathogenesis of this disease. (PMID:24994465)
• IL-17 and IL-35 may be critically involved in the pathogenesis of hepatitis B-related LC. (PMID:25323532)
• The levels of EBI3 and IL-12p35 mRNAs in peripheral blood mononuclear cells in moderate or hyper-responders were significantly higher than those in non- or hypo-responders. (PMID:25575066)
• IL35 appears to contribute to the loss of immunological self-tolerance in ITP patients by modulating T cells and immunoregulatory cytokines. (PMID:25640666)
• IL-35 is highly expressed in chronic HBV CD4(+) T-cells and plays an important role in the inhibition of the cellular immune response in chronic HBV. (PMID:25869609)
• IL-35 mRNA and protein were higher in tuberculous pleural effusions than in malignant ones. (PMID:25935866)
• EBI3 gene rs4740 polymorphism is closely associated with susceptibility to pulmonary tuberculosis and the elevation and enrichment of EBI3 in the lung derived from macrophages may contribute to the exacerbation of mycobacterial infection. (PMID:25937126)
• IL-35 can effectively suppress the proliferation and IL-4 production of activated CD4+CD25- T cells in allergic asthma, and that IL-35 may be a new immunotherapy for asthma patients. (PMID:26044961)
• Elevated circulating IL-35, particularly at early phase, its decrease after treatment initiation, and a positive association between synovial fluid IL-35 and disease activity support an involvement of IL-35 in the pathogenesis of RA. (PMID:26204444)
• Data suggest that the toll like receptor 3 (TLR3)-interferon regulatory factor 6 protein (IRF6)-interleukin-23 subunit p19 (p19)/EBI3 protein axis may regulate keratinocyte functions in the skin. (PMID:26303210)
• EBI3 Downregulation Contributes to Type I Collagen Overexpression in Scleroderma Skin. (PMID:26355156)
• IL-35 was elevated in bone marrow of adult AML patients and this increase was correlated with the clinical stages of malignancy, suggesting that IL-35 is involved in pathogenesis of AML. (PMID:26431888)
• higher decidual mRNA expression in preeclampsia (PMID:26472010)
• Data show that interleukin-35 (Epstein-Barr virus-induced gene 3 (EBI3) and the interleukin-12 Subunit p35 (p35) subunit) levels were significantly elevated in the patients with influenza infection. (PMID:26844658)
• The plasma levels of interleukin-35 were significantly higher in the hepatocellular carcinoma patients than the controls. (PMID:27699510)
• this study introduces IL-35 as a new treatment for pemphigus (PMID:27855302)
• The study revealed that post-therapeutic recovery of circulating IL-35 concentration might be an independent predictor for effective response to IST in pediatric AA. (PMID:28211781)
• over-expression of EBI3 could reduce the apoptosis of Treg/CD4(+)T/CD8(+)T cells and prevent radiation-induced immunosuppression of cervical cancer HeLa cells by inhibiting the activation of PD-1/PD-L1 signaling pathway (PMID:28351328)
• IL-35 expression was significantly increased in patients with chronic hepatitis C and was positively correlated with the levels of viral RNA (PMID:28644966)
• Letter: circulating IL-35 is significantly higher than healthy controls and associate with disease activity in systemic lupus erythematosus. (PMID:28752680)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ebi3	ENSDARG00000053620
mus_musculus	Ebi3	ENSMUSG00000003206
rattus_norvegicus	Ebi3	ENSRNOG00000050509

Paralogs (23): CRLF1 (ENSG00000006016), IL12RB2 (ENSG00000081985), IL5RA (ENSG00000091181), IL12RB1 (ENSG00000096996), IL27RA (ENSG00000104998), 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 subunit beta — Q14213 (reviewed: Q14213)

Alternative names: Epstein-Barr virus-induced gene 3 protein

All UniProt accessions (1): Q14213

UniProt curated annotations — full annotation on UniProt →

Function. Associates with IL27 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity. IL-27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that has diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17). It drives rapid clonal expansion of naive but not memory CD4 T-cells. It also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines.

Subunit / interactions. Heterodimer with IL27/IL27A; not disulfide-linked. This heterodimer is known as interleukin IL-27. Heterodimer with IL12A; not disulfide-linked. This heterodimer is known as interleukin IL-35. Interacts with SQSTM1.

Subcellular location. Secreted.

Induction. By Epstein-Barr virus (EBV).

Similarity. Belongs to the type I cytokine receptor family. Type 3 subfamily.

RefSeq proteins (1): NP_005746* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003530	Hematopoietin_rcpt_L_F3_CS	Conserved_site
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR053073	IL11/IL27_subunit_beta	Family
IPR056621	FN3_IL27B_N	Domain

Pfam: PF00041, PF24031

UniProt features (28 total): strand 15, turn 3, domain 2, glycosylation site 2, sequence variant 2, signal peptide 1, chain 1, helix 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7ZXK	X-RAY DIFFRACTION	2.2
8XWY	X-RAY DIFFRACTION	3.4
7U7N	ELECTRON MICROSCOPY	3.47
8D85	ELECTRON MICROSCOPY	3.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14213-F1	88.34	0.72

Antibody-complex structures (SAbDab): 1 — 7ZXK

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 (2): 55, 105

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: 353 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_B_CELL_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GCM_MYCL1, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION

GO Biological Process (8): humoral immune response (GO:0006959), positive regulation of type II interferon production (GO:0032729), T-helper 1 type immune response (GO:0042088), T cell proliferation (GO:0042098), positive regulation of alpha-beta T cell proliferation (GO:0046641), immune system process (GO:0002376), signal transduction (GO:0007165), cytokine-mediated signaling pathway (GO:0019221)

GO Molecular Function (4): cytokine receptor activity (GO:0004896), cytokine activity (GO:0005125), interleukin-27 receptor binding (GO:0045523), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), 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
cellular anatomical structure	2
immune response	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
T cell activation	1
lymphocyte proliferation	1
positive regulation of T cell proliferation	1
alpha-beta T cell proliferation	1
positive regulation of alpha-beta T cell activation	1
regulation of alpha-beta T cell proliferation	1
biological_process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
transmembrane signaling receptor activity	1
cytokine-mediated signaling pathway	1
cytokine binding	1
immune receptor activity	1
receptor ligand activity	1
cytokine receptor binding	1
binding	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EBI3	IL27	Q8NEV9	994
EBI3	IL12A	P29459	785
EBI3	IL27RA	Q6UWB1	727
EBI3	IL12RB2	Q99665	475
EBI3	IL23A	Q9NPF7	473
EBI3	CRLF3	Q8IUI8	351
EBI3	IL10	P22301	348
EBI3	FOXP3	Q9BZS1	319
EBI3	IL6	P05231	318
EBI3	STAT1	P42224	317
EBI3	IFNG	P01579	311
EBI3	CD4	P01730	307
EBI3	IL6ST	P40189	288
EBI3	IL17A	Q16552	275
EBI3	NBPF4	Q96M43	274

IntAct

21 interactions, top by confidence:

A	B	Type	Score
HLA-G	B2M	psi-mi:“MI:0915”(physical association)	0.780
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
IL27RA	IL6ST	psi-mi:“MI:0914”(association)	0.590
IL27RA	IL6ST	psi-mi:“MI:0915”(physical association)	0.590
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
IL12A	EBI3	psi-mi:“MI:0915”(physical association)	0.400
IL27	EBI3	psi-mi:“MI:0915”(physical association)	0.400
EBI3	SMAD3	psi-mi:“MI:0915”(physical association)	0.370
MDFI	EBI3	psi-mi:“MI:0915”(physical association)	0.370
EBI3	ZZEF1	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DNAJA2	ENC1	psi-mi:“MI:0914”(association)	0.350
FBXO6	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SLC18A1	USP1	psi-mi:“MI:0914”(association)	0.350
TUBB	VWA8	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	ARHGAP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): EBI3 (Two-hybrid), IL27 (Affinity Capture-Western), EBI3 (Affinity Capture-Western), EBI3 (Affinity Capture-Western), CANX (Affinity Capture-Western), IL27RA (Affinity Capture-Western), ARMC8 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), PRKCD (Affinity Capture-MS), MAEA (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), ZMYND19 (Affinity Capture-MS), S100P (Reconstituted Complex), S100A6 (Reconstituted Complex), EBI3 (Reconstituted Complex)

ESM2 similar proteins: A0A140LHF2, O35228, O70394, P0DP72, P14753, P21183, P22272, P22273, P26951, P26952, P31785, P34902, P40223, P40238, P40321, P42701, P55144, P55146, Q00941, Q00993, Q01114, Q06418, Q07303, Q08351, Q14213, Q14773, Q2KL21, Q5NKT8, Q60837, Q6UWB1, Q6UXL0, Q6ZVW7, Q7TNI4, Q80XF5, Q8K4C2, Q8MJS1, Q91ZV8, Q92154, Q923P0, Q95118

Diamond homologs: O02744, P29460, P43432, P46282, P46658, P48095, P68220, P68221, Q14213, Q28234, Q28268, Q28938, Q2PE76, Q61729, Q865W9, Q865Y3, Q866G3, Q8CJE6, Q91ZK7, Q924V5, Q9XSQ5, O35228, O88507, P26992, P51641, P70225, Q08406, Q14626, Q5RF19, Q64385, Q71DR4, Q99MF4, O18796, P08887, P22272, P22273, Q62959, Q9MYL0, D3YYU8, O02671

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

485 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4229614:A:T	donor_gain	1.0000
19:4229615:AAGGT:A	donor_loss	1.0000
19:4229618:G:C	donor_loss	1.0000
19:4229619:T:A	donor_loss	1.0000
19:4233308:G:GG	donor_gain	1.0000
19:4234640:T:TA	acceptor_gain	1.0000
19:4234653:T:A	acceptor_gain	1.0000
19:4234665:A:AG	acceptor_gain	1.0000
19:4234666:G:GA	acceptor_gain	1.0000
19:4234666:GTC:G	acceptor_gain	1.0000
19:4234666:GTCA:G	acceptor_gain	1.0000
19:4234666:GTCAA:G	acceptor_gain	1.0000
19:4236932:TCAGG:T	acceptor_loss	1.0000
19:4236934:AGGTG:A	acceptor_gain	1.0000
19:4236935:GGTGG:G	acceptor_gain	1.0000
19:4229613:GAAAG:G	donor_gain	0.9900
19:4229618:G:GG	donor_gain	0.9900
19:4231189:A:AG	acceptor_gain	0.9900
19:4231189:AG:A	acceptor_gain	0.9900
19:4231190:G:GG	acceptor_gain	0.9900
19:4231190:GG:G	acceptor_gain	0.9900
19:4231385:GCCC:G	donor_gain	0.9900
19:4231440:GCC:G	donor_gain	0.9900
19:4233279:C:G	donor_gain	0.9900
19:4233303:CATCA:C	donor_gain	0.9900
19:4233304:ATCA:A	donor_gain	0.9900
19:4233305:TCA:T	donor_gain	0.9900
19:4234646:T:TA	acceptor_gain	0.9900
19:4234666:GT:G	acceptor_gain	0.9900
19:4234804:G:GT	donor_gain	0.9900

AlphaMissense

1468 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4234734:G:C	W149C	0.997
19:4234734:G:T	W149C	0.997
19:4231267:G:C	W48C	0.994
19:4231267:G:T	W48C	0.994
19:4234732:T:A	W149R	0.991
19:4234732:T:C	W149R	0.991
19:4234752:G:C	W155C	0.991
19:4234752:G:T	W155C	0.991
19:4237008:G:C	A204P	0.990
19:4234780:T:G	Y165D	0.989
19:4237049:G:C	W217C	0.987
19:4237049:G:T	W217C	0.987
19:4237041:A:C	S215R	0.985
19:4237043:T:A	S215R	0.985
19:4237043:T:G	S215R	0.985
19:4234781:A:C	Y165S	0.984
19:4237042:G:T	S215I	0.984
19:4237050:A:C	S218R	0.984
19:4237052:T:A	S218R	0.984
19:4237052:T:G	S218R	0.984
19:4234750:T:A	W155R	0.981
19:4234750:T:C	W155R	0.981
19:4234768:T:C	F161L	0.981
19:4234770:C:A	F161L	0.981
19:4234770:C:G	F161L	0.981
19:4233245:T:A	V106D	0.980
19:4237000:T:A	V201D	0.980
19:4231261:C:G	C46W	0.979
19:4231265:T:A	W48R	0.979
19:4231265:T:C	W48R	0.979

dbSNP variants (sampled 300 via entrez): RS1000037504 (19:4234193 G>A), RS1000097068 (19:4237335 C>A,G,T), RS1000180347 (19:4229970 G>A,C), RS1000636688 (19:4233083 G>A), RS1000691685 (19:4232115 C>T), RS1000711247 (19:4235958 C>T), RS1000748589 (19:4228510 C>G), RS1000755268 (19:4230853 G>A,C), RS1001296690 (19:4231103 G>C,T), RS1001547769 (19:4235581 T>A), RS1002328260 (19:4237182 T>A,C), RS1002518049 (19:4233007 T>C,G), RS1002589983 (19:4232261 G>A,C,T), RS1002634859 (19:4228565 C>A,G,T), RS1002821490 (19:4230882 A>C)

Disease associations

OMIM: gene MIM:605816 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_457	Blood protein levels	0.000000e+00
GCST009731_51	Blood protein levels in cardiovascular risk	5.000000e-119
GCST010173_165	Triglyceride levels	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008183	interleukin 27 receptor subunit alpha measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	3
nickel sulfate	decreases reaction, increases expression, affects reaction	2
entinostat	increases expression, affects cotreatment	2
Decitabine	affects expression, increases expression	2
Cisplatin	increases expression, affects expression, affects cotreatment	2
Lipopolysaccharides	affects response to substance, affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
Aflatoxin B1	increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
nickel chloride	increases expression	1
perfluorooctanoic acid	increases expression	1
tris(chloroethyl)phosphate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
pentanal	increases expression	1
tri-(2-chloroisopropyl)phosphate	increases expression	1
BAY 11-7085	decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8F1	Abcam HCT 116 EBI3 KO	Cancer cell line	Male
CVCL_B8V3	Abcam MCF-7 EBI3 KO	Cancer cell line	Female
CVCL_B9H9	Abcam A-549 EBI3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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