TNFRSF6B

Summary

TNFRSF6B (TNF receptor superfamily member 6b, HGNC:11921) is a protein-coding gene on chromosome 20q13.33, encoding Tumor necrosis factor receptor superfamily member 6B (O95407). Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL.

This gene belongs to the tumor necrosis factor receptor superfamily. The encoded protein is postulated to play a regulatory role in suppressing FasL- and LIGHT-mediated cell death. It acts as a decoy receptor that competes with death receptors for ligand binding. Over-expression of this gene has been noted in gastrointestinal tract tumors. Read-through transcription into this gene from the neighboring upstream gene, which encodes regulator of telomere elongation helicase 1 (RTEL1), generates a non-coding transcript.

Source: NCBI Gene 8771 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_003823

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11921
Approved symbol	TNFRSF6B
Name	TNF receptor superfamily member 6b
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	DcR3, DCR3, TR6, M68
Ensembl gene	ENSG00000243509
Ensembl biotype	protein_coding
OMIM	603361
Entrez	8771

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000369996, ENST00000878502, ENST00000878503, ENST00000878504, ENST00000878505, ENST00000964573

RefSeq mRNA: 1 — MANE Select: NM_003823 NM_003823

CCDS: CCDS13532

Canonical transcript exons

ENST00000369996 — 3 exons

Exon	Start	End
ENSE00002494994	63696652	63697191
ENSE00003487411	63698280	63698684
ENSE00003576664	63697328	63697522

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 86.45.

FANTOM5 (CAGE): breadth broad, TPM avg 13.6018 / max 502.9043, expressed in 685 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185848	13.4688	678
185847	0.1330	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	86.45	gold quality
spleen	UBERON:0002106	85.49	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.92	gold quality
right lung	UBERON:0002167	83.57	gold quality
upper lobe of left lung	UBERON:0008952	83.55	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.89	gold quality
vermiform appendix	UBERON:0001154	82.88	gold quality
adenohypophysis	UBERON:0002196	82.44	gold quality
pituitary gland	UBERON:0000007	82.23	gold quality
adipose tissue	UBERON:0001013	81.94	gold quality
amygdala	UBERON:0001876	81.71	gold quality
temporal lobe	UBERON:0001871	81.56	gold quality
hypothalamus	UBERON:0001898	81.20	gold quality
putamen	UBERON:0001874	81.12	gold quality
cerebellum	UBERON:0002037	80.90	gold quality
cerebellar cortex	UBERON:0002129	80.89	gold quality
cerebellar hemisphere	UBERON:0002245	80.86	gold quality
left uterine tube	UBERON:0001303	80.48	gold quality
omental fat pad	UBERON:0010414	80.45	gold quality
caudate nucleus	UBERON:0001873	79.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.49	silver quality
tibial nerve	UBERON:0001323	79.49	gold quality
Ammon’s horn	UBERON:0001954	79.32	gold quality
lower esophagus muscularis layer	UBERON:0035833	78.43	gold quality
lower esophagus	UBERON:0013473	78.36	gold quality
substantia nigra	UBERON:0002038	78.32	gold quality
right lobe of thyroid gland	UBERON:0001119	77.94	gold quality
left lobe of thyroid gland	UBERON:0001120	77.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TBX10

miRNA regulators (miRDB)

16 targeting TNFRSF6B, 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-3658	99.96	73.87	4379
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-3668	98.52	68.76	951
HSA-MIR-1265	98.36	66.46	598
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-2682-3P	97.10	66.16	840
HSA-MIR-7109-3P	94.23	67.19	743

Literature-anchored findings (GeneRIF, showing 40)

• As a soluble receptor.Fc fusion protein, DcR3 modulates dendritic cell differentiation and maturation from CD14+ monocytes by up-regulation of CD86/B7.2 and down-regulation of CD40, CD54/ICAM-1, CD80/B7.1, CD1a, and HLA-DR. (PMID:11994433)
• DCR3 is located on 20q13; when amplified in colorectal cancer, patients are less likely to respond to chemotherapy (PMID:12397645)
• Data show that mRNA encoding LIGHT and its receptors [HVEM, LTbetaR, and TR6 (DcR3)] are present in placentas and cytotrophoblast cells at term. (PMID:12466117)
• TR6 delivers costimulation through its ligand(s) on the T cell surface, and at least the major part of such costimulation is via LIGHT. (PMID:12471113)
• role in modulating immune cell interactions (PMID:12761893)
• DcR3 blocks the growth inhibition signals mediated by mFasL (PMID:12794752)
• Recombinant TR6 can inhibit T cell chemotaxis both in vitro and in vivo, an effect that is likely mediated by reverse signaling from TR6 to LIGHT on the T cell surface. (PMID:14500635)
• interferes with the differentiation and maturation of bone marrow-derived dendritic cells (PMID:14634066)
• phagocytic activity toward immune complexes and apoptotic bodies as well as the production of free radicals and proinflammatory cytokines in response to lipopolysaccharide were impaired in DcR3.Fc-treated monocyte-derived macrophages (PMID:14657214)
• data suggest a novel role for TR6 in immune responses to bacteria (PMID:14688085)
• DcR3 is able to induce actin reorganization and enhance the adhesion of monocytes by activating multiple signaling molecules, such as protein kinase C, phosphatidylinositol 3-kinase, focal adhesion kinase and Src kinases. (PMID:14697332)
• DCR3 and cIAP-2 protect trophoblast cells against LIGHT-mediated apoptosis. (PMID:15215185)
• athe ability of DCR3 to promote TRAIL-triggered death may be used to potentiate TRAIL efficacy during treatment tumors overexpressing DcR3. (PMID:15475369)
• The high DcR3 mRNA expression and protein expression may be positively related to the gene amplification in astrocytic brain tumors, especially glioblastomas. (PMID:15627206)
• DcR3 exerts a direct effect on endothelial cells in activating the NF-kappa B signal pathway, up-regulating transcription of adhesion molecules and IL-8 secretion, and enhancing monocyte adhesion. (PMID:15661928)
• significantly more overexpression of DcR3 in high-grade dysplasia or carcinoma in situ and esophageal adenocarcinoma (PMID:16040301)
• Dcr3 transgenic mice provide a model system for the study of modulatory effect of Dcr3 on host immune response in patients suffering from cancers and autoimmune diseases (PMID:16210617)
• LIGHT and two of its receptors, a membrane-bound receptor that mediates apoptosis (LTbetaR) and a soluble receptor that interferes with LIGHT signaling (DcR3), were present in syncytiotrophoblast and cytotrophoblast cells in all samples (PMID:17010447)
• DcR3 expressed in rheumatoid arthritis fibroblast-like synoviocytes is increased by TNFalpha by protecting the cells against Fas-induced apoptosis; DcR3 may be a therapeutic target in rheumatoid arthritis. (PMID:17393415)
• DCR3 prevents and protects kidney in autoimmune crescentic glomerulonephritis through modulation of T cell activation/proliferation, B cell activation, inhibition of apoptosis, and suppression of mononuclear leukocyte infiltration. (PMID:17687076)
• Expression of DcR3 protein in laryngeal carcinoma tissues was obviously higher than those in para-carcinoma and normal laryngeal mucosa tissues. (PMID:17802823)
• DcR3 overexpression could lead to an systemic lupus erythematosus-like syndrome in transgenic mice (PMID:17968950)
• elucidates a novel mechanism of DcR3-mediated immunosuppression (PMID:18006694)
• Gastric cancer patients with high DcR3 expression presented more advanced pN2 disease than those with low DcR3 expression. (PMID:18251184)
• variants of IL5RA and TNFRSF6B may predispose to sporadic IgA nephropathy (PMID:18256354)
• role of DcR3 in the development of tumor-associated macrophages (PMID:18349319)
• High DcR3 expression is associated with advanced stage gastric cancer (PMID:18376232)
• diagnostic parameter for systemic lupus erythematosus (PMID:18562337)
• overexpression of DcR3 is associated with a worse prognosis in diffuse large B cell lymphoma and the possible mechanism may act through the increase of chemo-resistance of lymphoma cells (PMID:18695885)
• Severe rhaumatoid arthritis stage was associated with highly elevated TL1A and DcR3 serum levels. (PMID:18757243)
• TNFRSF6B gene variants are associated with pediatric-onset inflammatory bowel disease. (PMID:18758464)
• The assessment of DcR3 expression levels offers valuable prognostic information that could be used to select patients for adjuvant therapy studies. (PMID:18813347)
• DcR3 is over-expressed in human GC and positively correlated with development and metastases of gastric lesions (PMID:18991242)
• Elevated levels of DcR3 in tissue are positively correlated with hepatocellular carcinoma growth. (PMID:19093253)
• DcR3 expression varies during the menstrual cycle and is regulated by sex steroid hormones in vitro in endometrial cells; decidual DcR3 protein was lower in anembryonic than normal pregnancies (PMID:19246462)
• The anti-inflammatory properties and high DcR3 concentrations in the CSF warrant further investigations in the expression pattern and the function of DcR3 within the CNS. (PMID:19269042)
• DcR3 mRNAs were detected by Reverse transcription polymerase chain reaction and their surface expressions were measured by flow cytometry (PMID:19305072)
• Overexpression of Decoy receptor 3 enhances nasopharyngeal carcinoma cell migration and invasion. (PMID:19483191)
• evidence of the expression of DcR3 in multiple myeloma, and the involvement of this molecule in supporting the survival and formation of osteoclasts from multiple myeloma bone disease patients (PMID:19587706)
• High plasma DcR3(decoy receptor 3 ) levels correlate with development of multiple-organ dysfunction and predict the 28-day mortality in patients with Acute respiratory distress syndrome. (PMID:19644047)

Cross-species orthologs

0 orthologs

Paralogs (21): FAS (ENSG00000026103), TNFRSF1B (ENSG00000028137), TNFRSF9 (ENSG00000049249), RELT (ENSG00000054967), NGFR (ENSG00000064300), TNFRSF1A (ENSG00000067182), CD40 (ENSG00000101017), TNFRSF10A (ENSG00000104689), LTBR (ENSG00000111321), TNFRSF10B (ENSG00000120889), TNFRSF8 (ENSG00000120949), CD27 (ENSG00000139193), TNFRSF11A (ENSG00000141655), TNFRSF21 (ENSG00000146072), TNFRSF14 (ENSG00000157873), TNFRSF11B (ENSG00000164761), TNFRSF10D (ENSG00000173530), TNFRSF10C (ENSG00000173535), TNFRSF4 (ENSG00000186827), TNFRSF18 (ENSG00000186891), TNFRSF25 (ENSG00000215788)

Protein

Protein identifiers

Tumor necrosis factor receptor superfamily member 6B — O95407 (reviewed: O95407)

Alternative names: Decoy receptor 3, Decoy receptor for Fas ligand, M68

All UniProt accessions (1): O95407

UniProt curated annotations — full annotation on UniProt →

Function. Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL. Protects against apoptosis.

Subcellular location. Secreted.

Tissue specificity. Detected in fetal lung, brain and liver. Detected in adult stomach, spinal cord, lymph node, trachea, spleen, colon and lung. Highly expressed in several primary tumors from colon, stomach, rectum, esophagus and in SW480 colon carcinoma cells.

RefSeq proteins (1): NP_003814* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR034023	TNFRSF6B_N	Domain
IPR052459	TNFRSF_decoy_receptor	Family

Pfam: PF00020

UniProt features (36 total): strand 18, disulfide bond 9, repeat 4, signal peptide 1, chain 1, turn 1, helix 1, glycosylation site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
4KGQ	X-RAY DIFFRACTION	2.27
4J6G	X-RAY DIFFRACTION	2.4
3K51	X-RAY DIFFRACTION	2.45
4MSV	X-RAY DIFFRACTION	2.5
4KGG	X-RAY DIFFRACTION	2.78
3MHD	X-RAY DIFFRACTION	2.9
3MI8	X-RAY DIFFRACTION	2.95
5L36	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95407-F1	87.21	0.74

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 (9): 91–105, 95–113, 115–126, 132–150, 153–168, 174–193, 49–62, 52–70, 73–88

Glycosylation sites (1): 173

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5669034	TNFs bind their physiological receptors

MSigDB gene sets: 54 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, MODULE_379, FOURNIER_ACINAR_DEVELOPMENT_LATE_DN, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_INFLAMMATORY_RESPONSE, MODULE_88, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, RYTTCCTG_ETS2_B, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE, MODULE_242, KOBAYASHI_EGFR_SIGNALING_24HR_DN, NERF_Q2

GO Biological Process (2): apoptotic process (GO:0006915), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TNFR2 non-canonical NF-kB pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
molecular transducer activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFRSF6B	TNFSF15	O95150	998
TNFRSF6B	FASLG	P48023	997
TNFRSF6B	TNFSF14	O43557	951
TNFRSF6B	TNFRSF25	P78507	836
TNFRSF6B	TNFRSF1A	P19438	718
TNFRSF6B	TNFSF8	P32971	708
TNFRSF6B	TNF	P01375	678
TNFRSF6B	STMN1	P16949	670
TNFRSF6B	NR2C2	P49116	608
TNFRSF6B	PSMG1	O95456	593
TNFRSF6B	IL1A	P01583	580
TNFRSF6B	TNFSF10	P50591	571
TNFRSF6B	LTB	P78370	531
TNFRSF6B	TNFRSF14	Q92956	513
TNFRSF6B	TNFRSF10C	O14798	507

IntAct

38 interactions, top by confidence:

A	B	Type	Score
TNFRSF6B	TNFSF14	psi-mi:“MI:0407”(direct interaction)	0.720
TNFSF14	TNFRSF6B	psi-mi:“MI:0407”(direct interaction)	0.720
TNFRSF6B	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF6B		psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	TNFRSF6B	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF6B	TNFSF15	psi-mi:“MI:0407”(direct interaction)	0.560
TNFSF14	TNFRSF6B	psi-mi:“MI:0915”(physical association)	0.520
TNFRSF6B	FASLG	psi-mi:“MI:0407”(direct interaction)	0.440
SIGLEC10	TNFRSF6B	psi-mi:“MI:0915”(physical association)	0.400
KLHL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
EDN3	POTEF	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	ZNF316	psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350
ELSPBP1	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
OIT3	WNT10B	psi-mi:“MI:0914”(association)	0.350
SLURP1	MAN2B1	psi-mi:“MI:0914”(association)	0.350
CLEC2B	ADAM10	psi-mi:“MI:0914”(association)	0.350
ARSA	CLGN	psi-mi:“MI:0914”(association)	0.350
CST11	PLXNB2	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): KRTAP10-9 (Two-hybrid), KRTAP10-3 (Two-hybrid), Tnfsf14 (Affinity Capture-Western), TNFRSF6B (Reconstituted Complex), TNFRSF6B (Two-hybrid), TNFRSF6B (Affinity Capture-RNA), TNFRSF6B (Affinity Capture-Western), TNFSF14 (Affinity Capture-Western), FASLG (Affinity Capture-Western), TNFRSF6B (Affinity Capture-Western), TNFRSF6B (Affinity Capture-MS), TNFRSF6B (Affinity Capture-MS), TNFSF14 (Affinity Capture-Western), FASLG (Affinity Capture-Western), FASLG (Affinity Capture-Western)

ESM2 similar proteins: A4FV93, A5A8Y8, B2LW77, D3ZUK3, O00468, O70534, O75074, O88204, O88839, O95407, P06579, P07204, P15306, P60882, P80370, Q09163, Q13444, Q14162, Q3SWY4, Q501P1, Q53RD9, Q5ND28, Q5VY43, Q5W7P8, Q61810, Q6AZ60, Q6GUQ1, Q6MG84, Q6UY11, Q71U07, Q75N90, Q7Z7M0, Q8K1E3, Q8K1S7, Q8K4G1, Q8NCW0, Q8ND94, Q8VIK5, Q8WUT4, Q93038

Diamond homologs: A5D7R1, D3ZF92, O00300, O08712, O08727, O35305, O75509, O95407, P0DTN0, P20333, P25119, P25942, P25943, P27512, P29825, P36941, P43489, P83626, Q28203, Q3LRP1, Q3ZTK5, Q63199, Q7YRL5, Q8SQ34, Q9EPU5, Q9Y6Q6, Q80WM9, O73559, P0DSV7, P0DSV8, P68636, P68637, P28908, P07174, P08138, P15725, P20334, P47741, P50284, Q07011

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TNFRSF6B	down-regulates	TNFSF15	binding
TNFRSF6B	down-regulates	FASLG	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

652 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63697190:GG:G	donor_gain	1.0000
20:63697191:GG:G	donor_gain	1.0000
20:63697319:T:A	acceptor_gain	1.0000
20:63697172:TGCCG:T	donor_gain	0.9900
20:63697173:GCCGG:G	donor_gain	0.9900
20:63697174:CCGGC:C	donor_gain	0.9900
20:63697189:CGGG:C	donor_loss	0.9900
20:63697190:GGGTG:G	donor_loss	0.9900
20:63697191:GGT:G	donor_loss	0.9900
20:63697191:GGTGA:G	donor_loss	0.9900
20:63697192:G:C	donor_loss	0.9900
20:63697192:G:GG	donor_gain	0.9900
20:63697193:T:A	donor_loss	0.9900
20:63697319:T:TA	acceptor_gain	0.9900
20:63697320:G:A	acceptor_gain	0.9900
20:63697325:CA:C	acceptor_loss	0.9900
20:63697326:A:AG	acceptor_gain	0.9900
20:63697326:AGGC:A	acceptor_loss	0.9900
20:63697327:G:GG	acceptor_gain	0.9900
20:63697327:GGC:G	acceptor_gain	0.9900
20:63697518:ACCAG:A	donor_loss	0.9900
20:63697520:CAG:C	donor_loss	0.9900
20:63697520:CAGGT:C	donor_loss	0.9900
20:63697521:AGGTG:A	donor_loss	0.9900
20:63697522:GGT:G	donor_loss	0.9900
20:63697522:GGTGA:G	donor_loss	0.9900
20:63697523:G:A	donor_loss	0.9900
20:63698273:A:AG	acceptor_gain	0.9900
20:63698279:GGA:G	acceptor_gain	0.9900
20:63697182:A:AG	donor_gain	0.9800

AlphaMissense

1897 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63697016:C:A	N83K	0.995
20:63697016:C:G	N83K	0.995
20:63697375:T:C	F158L	0.994
20:63697377:C:A	F158L	0.994
20:63697377:C:G	F158L	0.994
20:63696930:G:T	G55C	0.991
20:63697015:A:T	N83I	0.990
20:63697376:T:G	F158C	0.988
20:63696931:G:T	G55V	0.987
20:63697013:G:C	W82C	0.987
20:63697013:G:T	W82C	0.987
20:63697125:T:C	F120L	0.984
20:63697127:C:A	F120L	0.984
20:63697127:C:G	F120L	0.984
20:63697000:A:G	Y78C	0.983
20:63697039:G:A	C91Y	0.983
20:63697029:T:A	C88S	0.982
20:63697030:G:C	C88S	0.982
20:63696921:T:A	C52S	0.980
20:63696922:G:C	C52S	0.980
20:63697405:T:A	C168S	0.980
20:63697406:G:C	C168S	0.980
20:63696936:T:C	F57L	0.979
20:63696938:T:A	F57L	0.979
20:63696938:T:G	F57L	0.979
20:63697110:T:A	C115S	0.979
20:63697111:G:C	C115S	0.979
20:63697096:A:T	N110I	0.978
20:63697480:T:A	C193S	0.978
20:63697481:G:C	C193S	0.978

dbSNP variants (sampled 300 via entrez): RS1000273367 (20:63699173 T>G), RS1000624496 (20:63696278 G>A), RS1001515087 (20:63698801 C>G), RS1001674915 (20:63695903 T>G), RS1001735960 (20:63698991 C>T), RS1001842434 (20:63698197 G>A), RS1002125851 (20:63696042 C>G,T), RS1002980369 (20:63697683 C>G,T), RS1003786111 (20:63697643 T>A,C,G), RS1004281355 (20:63696633 A>C,G), RS1005124908 (20:63698601 C>A,T), RS1005725681 (20:63696619 C>T), RS1006214570 (20:63698812 T>A,C), RS1006744801 (20:63697669 C>T), RS1006901190 (20:63696411 C>A,T)

Disease associations

OMIM: gene MIM:603361 | disease phenotypes: MIM:615190

GenCC curated gene-disease

Mondo (2): long QT syndrome (MONDO:0002442), dyskeratosis congenita, autosomal recessive 5 (MONDO:0014076)

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000225_1	Inflammatory bowel disease	9.000000e-15
GCST000964_24	Ulcerative colitis	2.000000e-10
GCST001633_3	Glioma	1.000000e-10
GCST001725_68	Inflammatory bowel disease	1.000000e-23
GCST001942_22	Prostate cancer	4.000000e-16
GCST002737_7	Atopic dermatitis	8.000000e-10
GCST003097_33	Pediatric autoimmune diseases	9.000000e-07
GCST003184_28	Atopic dermatitis	2.000000e-09
GCST003184_35	Atopic dermatitis	7.000000e-13
GCST004131_34	Inflammatory bowel disease	3.000000e-26
GCST004132_110	Crohn’s disease	3.000000e-13
GCST004133_15	Ulcerative colitis	9.000000e-17
GCST005537_58	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2.000000e-30
GCST006585_2588	Blood protein levels	2.000000e-08
GCST007563_15	Allergic disease (asthma, hay fever or eczema)	3.000000e-08
GCST007564_6	Asthma or allergic disease (pleiotropy)	3.000000e-10
GCST008916_69	Asthma	3.000000e-09
GCST009720_73	Asthma	7.000000e-09
GCST010002_71	Refractive error	1.000000e-14
GCST010090_5	Atopic dermatitis	8.000000e-17

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

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 — Tumour necrosis factor (TNF) receptor family

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
picrasidine I	increases expression, decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
3,19-(2-bromobenzylidene)andrographolide	decreases expression, decreases response to substance	1
bisphenol A	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
coronarin D	increases expression	1
Arsenic Trioxide	decreases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	decreases expression	1
Copper	affects binding, increases expression	1
Disulfiram	affects binding, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Menthol	decreases expression	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Sarin	increases expression	1
Smoke	decreases expression, increases abundance	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	increases methylation	1
Topotecan	affects response to substance	1
1-Butanol	increases abundance, increases expression, affects cotreatment	1
Particulate Matter	increases expression, affects cotreatment, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea