TNFRSF10C

Summary

TNFRSF10C (TNF receptor superfamily member 10c, HGNC:11906) is a protein-coding gene on chromosome 8p21.3, encoding Tumor necrosis factor receptor superfamily member 10C (O14798). Receptor for the cytotoxic ligand TRAIL.

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain and a transmembrane domain, but no cytoplasmic death domain. This receptor is not capable of inducing apoptosis, and is thought to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis. This gene was found to be a p53-regulated DNA damage-inducible gene. The expression of this gene was detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL.

Source: NCBI Gene 8794 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_003841

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11906
Approved symbol	TNFRSF10C
Name	TNF receptor superfamily member 10c
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	DcR1, TRAILR3, LIT, TRID, CD263
Ensembl gene	ENSG00000173535
Ensembl biotype	protein_coding
OMIM	603613
Entrez	8794

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000356864, ENST00000517558, ENST00000518135, ENST00000877636

RefSeq mRNA: 1 — MANE Select: NM_003841 NM_003841

CCDS: CCDS6037

Canonical transcript exons

ENST00000356864 — 5 exons

Exon	Start	End
ENSE00001487240	23116641	23117445
ENSE00003565944	23115508	23115616
ENSE00003573140	23111720	23111825
ENSE00003601121	23114657	23114770
ENSE00003902983	23102921	23103181

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 98.23.

FANTOM5 (CAGE): breadth broad, TPM avg 9.3092 / max 1458.6918, expressed in 914 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87882	8.9695	869
87881	0.1702	70
87883	0.1695	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	98.23	gold quality
granulocyte	CL:0000094	91.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.46	gold quality
periodontal ligament	UBERON:0008266	88.65	gold quality
bone marrow	UBERON:0002371	87.86	gold quality
leukocyte	CL:0000738	87.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.20	gold quality
monocyte	CL:0000576	87.05	gold quality
mononuclear cell	CL:0000842	86.55	gold quality
spleen	UBERON:0002106	85.24	gold quality
gall bladder	UBERON:0002110	84.21	gold quality
bone marrow cell	CL:0002092	84.09	gold quality
trabecular bone tissue	UBERON:0002483	80.31	gold quality
vermiform appendix	UBERON:0001154	78.22	gold quality
cervix squamous epithelium	UBERON:0006922	77.93	gold quality
upper lobe of left lung	UBERON:0008952	77.83	gold quality
right lung	UBERON:0002167	77.63	gold quality
diaphragm	UBERON:0001103	77.47	gold quality
caecum	UBERON:0001153	76.67	gold quality
upper lobe of lung	UBERON:0008948	76.41	gold quality
pancreatic ductal cell	CL:0002079	74.64	silver quality
buccal mucosa cell	CL:0002336	73.12	gold quality
palpebral conjunctiva	UBERON:0001812	72.38	gold quality
nasal cavity epithelium	UBERON:0005384	72.03	silver quality
omental fat pad	UBERON:0010414	71.98	gold quality
peritoneum	UBERON:0002358	71.96	gold quality
adipose tissue of abdominal region	UBERON:0007808	71.76	gold quality
apex of heart	UBERON:0002098	71.08	gold quality
smooth muscle tissue	UBERON:0001135	71.01	gold quality
ascending aorta	UBERON:0001496	70.94	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	538.25
E-ANND-3	yes	3.75
E-CURD-85	no	86.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2, TP53

miRNA regulators (miRDB)

24 targeting TNFRSF10C, 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-6888-3P	99.97	65.95	1170
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-6879-3P	93.93	64.00	759

Literature-anchored findings (GeneRIF, showing 32)

• TNF-related apoptosis-inducing ligand (TRAIL) is not constitutively expressed in the human brain, whereas both apoptosis-mediating and apoptosis-blocking TRAIL receptors are found on neurons, astrocytes, and oligodendrocytes (PMID:11844843)
• analysis of the transcription initiation sites and promoter structure of the TRAIL-R3 gene (PMID:12417331)
• Cytotoxicity and apoptosis induced by TRAIL to beta-cell lines CM were inhibited competitively by soluble TRAIL receptors, R1, R2, R3 or R4. (PMID:12488957)
• likely to be involved in chronic pancreatitis; pancreatic stellate cells may directly contribute to acinar regression by inducing apoptosis of parenchymal cells in a TRAIL-dependent manner (PMID:12808117)
• cloned and characterized a p53 consensus element located within the first intron of the TRAIL-R3 gene (PMID:14623878)
• Our results demonstrate that DcR1 and DcR2 genes are frequently methylated in various tumor types, and aberrant methylation was the cause for silencing of DcR1 and DcR2 expression. (PMID:14999791)
• The DcR1 had no death domain and was anchored to the membrane via a glycophosphatidyl inositol tail. (PMID:15538968)
• TRAIL-R4 but not TRAIL-R3 is the decoy receptor which appeared to influence TRAIL sensitivity in breast cancer cells (PMID:15916713)
• Resistance to TRAIL-induced apoptosis in acute myeloid leukemia cells is associated with expression of TRAIL-R3. (PMID:15921376)
• The specificity of DcR1- and DcR2-mediated TRAIL inhibition reveals an additional level of complexity for the regulation of TRAIL signaling. (PMID:16980609)
• tryptophol induces apoptosis through DR5 and the resistance of PBL to tryptophol-induced apoptosis might be due to competition from DcR1 (PMID:17690453)
• p53 negatively regulates oxaliplatin-mediated TRAIL-induced apoptotic activity through DcR1 upregulation. (PMID:18345033)
• These data strongly support a recent proposal that a segment at 8p21.3 contains crucial prostate cancer tumor suppressors. (PMID:18460741)
• TRAILR3 (TNF-related apoptosis inducing ligand receptor 3) levels were significantly higher in lung parenchyma in subjects with emphysema (PMID:18511705)
• Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (PMID:18590575)
• inactivation of TNFRSF10C by chromosomal deletion and promoter methylation may play an important role in prostate cancer development (PMID:19035483)
• Low DCR1 is associated with non-small cell lung cancer. (PMID:19661294)
• Results suggest that DcR1 expression occurs in a subset of endometrial carcinomas and may contribute to resistance to TRAIL-induced apoptosis. (PMID:19936781)
• Decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4-positive T cells, are positively correlated with patients’ DAS scores. (PMID:20799941)
• Data show that about 20% of AML patients highly expressed decoy receptor TRAIL-R3, which was strongly correlated to a shortened overall survival. (PMID:21281967)
• Primary EOC is associated to a lower TRAIL-R3 expression. (PMID:22555108)
• GATA4 and DcR1 promoter hypermethylation is tumor specific event in glioblastoma but they promoter methylation cannot be considered as a prognostic marker of glioblastoma survival. (PMID:23320456)
• The membrane expression of the TRAIL receptors DR4, DR5, DcR1 and DcR2 is greater in normal endometrium than endometrioid adenocarcinoma (EAC). The level of the receptors in EAC is not dependent on grading and staging and does not predict survival. (PMID:23584885)
• the results presented here claim for a relevant impact of aberrant methylation of decoy receptors in melanoma and allow to understand how the silencing of DcR1 and DcR2 is related to melanomagenesis. (PMID:24211571)
• DcR1 levels in serum sample which were significantly lower in AMD patients. (PMID:24534820)
• membrane expression more common in endometrioid endometrial cancer than in normal endometrium (PMID:24649804)
• DcR1 upregulation mediates temozolomide resistance. (PMID:25808868)
• DcRs regulate TRAIL sensitivity at a supracellular level (PMID:26050621)
• Results identified epigenetic inactivation of TNFRSF10C and TNFRSF10D in majority of cervical cancer cases. (PMID:26542757)
• High levels of TRAIL-R3 and CCR-2 expression in tumor epithelial cells identified patients with early breast cancer with poor outcomes. (PMID:28420351)
• TRAIL receptors are differentially regulated and clinically significant in gallbladder cancer. (PMID:32111400)
• Hepatitis B Virus (HBV) Upregulates TRAIL-R3 Expression in Hepatocytes Resulting in Escape From Both Cell Apoptosis and Suppression of HBV Replication by TRAIL. (PMID:35226068)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdr	ENSDARG00000004392
danio_rerio	tnfrsfa	ENSDARG00000004451
danio_rerio	cd40	ENSDARG00000054968
danio_rerio	nradd	ENSDARG00000057143
danio_rerio	tnfrsf1b	ENSDARG00000070165
danio_rerio	tnfrsf11a	ENSDARG00000087804
mus_musculus	Tnfrsf22	ENSMUSG00000010751
mus_musculus	Tnfrsf23	ENSMUSG00000037613
mus_musculus	Tnfrsf26	ENSMUSG00000045362
rattus_norvegicus	Tnfrsf26	ENSRNOG00000043486
rattus_norvegicus	Tnfrsf22	ENSRNOG00000070689

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), TNFRSF4 (ENSG00000186827), TNFRSF18 (ENSG00000186891), TNFRSF25 (ENSG00000215788), TNFRSF6B (ENSG00000243509)

Protein

Protein identifiers

Tumor necrosis factor receptor superfamily member 10C — O14798 (reviewed: O14798)

Alternative names: Antagonist decoy receptor for TRAIL/Apo-2L, Decoy TRAIL receptor without death domain, Decoy receptor 1, Lymphocyte inhibitor of TRAIL, TNF-related apoptosis-inducing ligand receptor 3, TRAIL receptor without an intracellular domain

All UniProt accessions (2): O14798, E5RJI1

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the cytotoxic ligand TRAIL. Lacks a cytoplasmic death domain and hence is not capable of inducing apoptosis. May protect cells against TRAIL mediated apoptosis by competing with TRAIL-R1 and R2 for binding to the ligand.

Subcellular location. Cell membrane.

Tissue specificity. Higher expression in normal tissues than in tumor cell lines. Highly expressed in peripheral blood lymphocytes, spleen, skeletal muscle, placenta, lung and heart.

Post-translational modifications. N-glycosylated and O-glycosylated.

RefSeq proteins (1): NP_003832* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR020465	TNFR_10	Family
IPR034024	TNFRSF10_N	Domain
IPR052491	TNFRSF10	Family

Pfam: PF00020

UniProt features (29 total): repeat 8, disulfide bond 7, glycosylation site 3, region of interest 2, compositionally biased region 2, sequence variant 2, signal peptide 1, chain 1, lipid moiety-binding region 1, propeptide 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14798-F1	72.22	0.37

Functional residue map

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

Post-translational modifications (1): 236

Disulfide bonds (7): 53–66, 69–85, 88–101, 91–109, 111–125, 128–141, 131–149

Glycosylation sites (3): 77, 140, 156

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6803211	TP53 Regulates Transcription of Death Receptors and Ligands

MSigDB gene sets: 103 (showing top): PEREZ_TP63_TARGETS, MODULE_45, MODULE_64, GOCC_CELL_SURFACE, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, chr8p21, MODULE_379, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, MODULE_88, PID_P53_DOWNSTREAM_PATHWAY, MODULE_242, MODULE_38, KERLEY_RESPONSE_TO_CISPLATIN_UP, PARENT_MTOR_SIGNALING_UP

GO Biological Process (3): TRAIL-activated apoptotic signaling pathway (GO:0036462), positive regulation of apoptotic process (GO:0043065), apoptotic process (GO:0006915)

GO Molecular Function (3): transmembrane signaling receptor activity (GO:0004888), TRAIL binding (GO:0045569), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), cell surface (GO:0009986), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Death Genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
extrinsic apoptotic signaling pathway via death domain receptors	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
signaling receptor activity	1
protein binding	1
binding	1
cell periphery	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFRSF10C	TNFSF10	P50591	956
TNFRSF10C	TNFRSF10B	O14763	858
TNFRSF10C	TNFRSF10A	O00220	742
TNFRSF10C	CFLAR	O15519	740
TNFRSF10C	TNF	P01375	649
TNFRSF10C	XIAP	P98170	629
TNFRSF10C	CASP8	Q14790	621
TNFRSF10C	TNFRSF10D	Q9UBN6	610
TNFRSF10C	DCXR	Q7Z4W1	583
TNFRSF10C	FADD	Q13158	582
TNFRSF10C	FASLG	P48023	570
TNFRSF10C	TNFRSF6B	O95407	507
TNFRSF10C	CASP7	P55210	499
TNFRSF10C	FAS	P25445	479
TNFRSF10C	CASP3	P42574	447

IntAct

83 interactions, top by confidence:

A	B	Type	Score
TNFSF10	TNFRSF10C	psi-mi:“MI:0407”(direct interaction)	0.620
TNFRSF10C	SGTA	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	ASZ1	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	KCNK5	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	TMEM80	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	SYAP1	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	GPR37L1	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	COQ9	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	AQP6	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	KCNJ6	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	DNAJC1	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	PDZK1IP1	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	MGST1	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	MRPS18B	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	GPR152	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	STOM	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	CD79A	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	CYB5R3	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	SLC30A4	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SRPK1	TNFRSF10C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
HAVCR1	TNFRSF10C	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF10C	SLC22A23	psi-mi:“MI:0914”(association)	0.350
LHFPL6	TNFRSF10C	psi-mi:“MI:0914”(association)	0.350

BioGRID (100): TNFRSF10C (Reconstituted Complex), TNFRSF10C (Two-hybrid), CXCL14 (Reconstituted Complex), TNFRSF10C (Two-hybrid), TNFRSF10C (Two-hybrid), APOA1 (Two-hybrid), FAM101B (Two-hybrid), TNFRSF10C (Two-hybrid), TNFRSF10C (Two-hybrid), TNFRSF10C (Two-hybrid), TNFRSF10C (Two-hybrid), ZHX1 (Two-hybrid), TNFRSF10C (Two-hybrid), TNFRSF10C (Two-hybrid), TNFRSF10C (Two-hybrid)

ESM2 similar proteins: A4H238, A4H241, B4DH59, O14763, O14798, O46598, O88799, P0C6Y7, P19467, P19957, P28908, P38565, P97881, Q02496, Q13342, Q14242, Q28983, Q2EG98, Q30KK3, Q4ZJY8, Q4ZJZ1, Q4ZJZ3, Q5FVR0, Q5QGU6, Q5W9T8, Q60401, Q62010, Q62170, Q6AXX0, Q6AXY3, Q6H9L7, Q6P752, Q8BP27, Q8BVC1, Q8N687, Q95152, Q96D42, Q96EQ9, Q9BXX2, Q9BXX3

Diamond homologs: O00220, O14763, O14798, P15725, P47741, P83626, Q9QZM4, Q9UBN6, O19131, P19438, P50555, Q80WM9, O00300, O77736, P25445, P25446, P51867, Q3ZTK5, Q63199, Q8SQ34, Q92956, Q9BDN0, Q9BDN4, Q9BDP2, Q9TSN4, O35305, P43489, P50284, Q9Y6Q6, O35714, Q9Y5U5, A5D7R1, O08712, O08727, P25943, P29825, Q9ER62, Q9ER63

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TNFRSF10C	down-regulates	TNFSF10	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

650 predictions. Top by Δscore:

Variant	Effect	Δscore
8:23103178:GCCA:G	donor_gain	1.0000
8:23103182:G:GG	donor_gain	1.0000
8:23114652:CCCA:C	acceptor_loss	1.0000
8:23114653:CCAG:C	acceptor_loss	1.0000
8:23114654:CA:C	acceptor_loss	1.0000
8:23114655:A:AC	acceptor_loss	1.0000
8:23114655:A:AG	acceptor_gain	1.0000
8:23114655:AG:A	acceptor_gain	1.0000
8:23114656:G:GG	acceptor_gain	1.0000
8:23114656:GG:G	acceptor_gain	1.0000
8:23114767:TCAGG:T	donor_loss	1.0000
8:23114769:AGGTA:A	donor_loss	1.0000
8:23114770:GGTAC:G	donor_loss	1.0000
8:23114771:GTAC:G	donor_loss	1.0000
8:23116117:GCC:G	donor_gain	1.0000
8:23116162:A:AG	donor_gain	1.0000
8:23103179:CCAG:C	donor_loss	0.9900
8:23103180:CAG:C	donor_loss	0.9900
8:23103181:AGT:A	donor_loss	0.9900
8:23103182:GT:G	donor_loss	0.9900
8:23103183:T:G	donor_loss	0.9900
8:23103184:G:GT	donor_loss	0.9900
8:23103186:G:C	donor_loss	0.9900
8:23111717:CAG:C	acceptor_loss	0.9900
8:23111821:AGCAG:A	donor_loss	0.9900
8:23111823:CAGGT:C	donor_loss	0.9900
8:23111824:AG:A	donor_loss	0.9900
8:23111825:GG:G	donor_loss	0.9900
8:23111826:G:GA	donor_loss	0.9900
8:23111827:T:A	donor_loss	0.9900

AlphaMissense

1692 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:23115573:T:C	F116L	0.997
8:23115575:C:A	F116L	0.997
8:23115575:C:G	F116L	0.997
8:23115558:T:A	C111S	0.985
8:23115559:G:C	C111S	0.985
8:23115574:T:G	F116C	0.985
8:23115552:T:A	C109S	0.980
8:23115553:G:C	C109S	0.980
8:23114743:T:A	C85S	0.979
8:23114744:G:C	C85S	0.979
8:23111816:T:A	C53S	0.977
8:23111817:G:C	C53S	0.977
8:23115600:T:A	C125S	0.977
8:23115601:G:C	C125S	0.977
8:23115528:T:A	C101S	0.975
8:23115529:G:C	C101S	0.975
8:23114761:T:A	C91S	0.974
8:23114762:G:C	C91S	0.974
8:23114745:C:G	C85W	0.972
8:23114686:T:A	C66S	0.970
8:23114687:G:C	C66S	0.970
8:23114695:T:A	C69S	0.970
8:23114696:G:C	C69S	0.970
8:23114752:T:A	C88S	0.970
8:23114753:G:C	C88S	0.970
8:23115511:A:C	Q95P	0.970
8:23115530:C:G	C101W	0.970
8:23114754:T:G	C88W	0.968
8:23115558:T:C	C111R	0.968
8:23114659:T:C	S57P	0.967

dbSNP variants (sampled 300 via entrez): RS1000030867 (8:23113769 T>A), RS1000355685 (8:23115969 G>C), RS1000391350 (8:23116162 A>G), RS1000615086 (8:23117492 T>C), RS1000680125 (8:23103413 C>A,T), RS1000694016 (8:23117210 G>A), RS1000740107 (8:23110300 G>A), RS1000834069 (8:23111183 G>A,T), RS1001472248 (8:23115296 A>G), RS1001743331 (8:23110241 T>C,G), RS1001757441 (8:23115721 A>G), RS1001904078 (8:23117728 G>C), RS1001968677 (8:23116419 G>A), RS1002078868 (8:23112186 T>A), RS1002421926 (8:23105733 C>G)

Disease associations

OMIM: gene MIM:603613 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST004600_40	Eosinophil percentage of white cells	2.000000e-10
GCST004606_164	Eosinophil count	1.000000e-14
GCST004610_163	White blood cell count	1.000000e-11
GCST004613_116	Sum neutrophil eosinophil counts	3.000000e-12
GCST004614_45	Granulocyte count	3.000000e-12
GCST004618_77	White blood cell count (basophil)	6.000000e-12
GCST004620_13	Sum basophil neutrophil counts	1.000000e-10
GCST004623_114	Neutrophil percentage of granulocytes	3.000000e-09
GCST004624_123	Sum eosinophil basophil counts	3.000000e-18
GCST004626_108	Myeloid white cell count	4.000000e-12
GCST004629_122	Neutrophil count	1.000000e-10
GCST90002379_116	Basophil count	2.000000e-19
GCST90002381_367	Eosinophil count	2.000000e-41
GCST90002382_170	Eosinophil percentage of white cells	7.000000e-29
GCST90002394_323	Monocyte percentage of white cells	5.000000e-18
GCST90002397_324	Mean spheric corpuscular volume	3.000000e-11
GCST90002398_398	Neutrophil count	9.000000e-30
GCST90002407_499	White blood cell count	8.000000e-35
GCST90002407_500	White blood cell count	2.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0004833	neutrophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0007989	monocyte percentage of leukocytes

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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression, increases methylation	3
Doxorubicin	affects expression, increases expression	3
Valproic Acid	affects cotreatment, increases expression	3
bisphenol A	affects expression, increases methylation	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Ozone	decreases expression, decreases reaction, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	decreases expression, increases expression	2
Antirheumatic Agents	decreases expression	2
CSC-3436	decreases expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
trimellitic anhydride	increases expression	1
sodium arsenite	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
usnic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
CP 31398	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
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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