TNFRSF10D

Summary

TNFRSF10D (TNF receptor superfamily member 10d, HGNC:11907) is a protein-coding gene on chromosome 8p21.3, encoding Tumor necrosis factor receptor superfamily member 10D (Q9UBN6). 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, a transmembrane domain, and a truncated cytoplamic death domain. This receptor does not induce apoptosis, and has been shown to play an inhibitory role in TRAIL-induced cell apoptosis.

Source: NCBI Gene 8793 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_003840

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11907
Approved symbol	TNFRSF10D
Name	TNF receptor superfamily member 10d
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	DcR2, TRUNDD, TRAILR4, CD264
Ensembl gene	ENSG00000173530
Ensembl biotype	protein_coding
OMIM	603614
Entrez	8793

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000312584, ENST00000870290

RefSeq mRNA: 1 — MANE Select: NM_003840 NM_003840

CCDS: CCDS6038

Canonical transcript exons

ENST00000312584 — 9 exons

Exon	Start	End
ENSE00001203508	23144450	23144635
ENSE00001203514	23145058	23145089
ENSE00001203520	23145668	23145921
ENSE00001203527	23146961	23147072
ENSE00001221758	23154874	23154979
ENSE00001221777	23163786	23164027
ENSE00001311135	23135588	23138003
ENSE00001661145	23138188	23138260
ENSE00001758987	23148438	23148551

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 93.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.8519 / max 496.7846, expressed in 1532 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92287	36.8519	1532

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	93.68	gold quality
epithelial cell of pancreas	CL:0000083	91.80	gold quality
stromal cell of endometrium	CL:0002255	90.46	gold quality
pancreatic ductal cell	CL:0002079	87.10	silver quality
islet of Langerhans	UBERON:0000006	82.15	gold quality
ileal mucosa	UBERON:0000331	81.21	gold quality
right lobe of liver	UBERON:0001114	81.09	gold quality
endothelial cell	CL:0000115	80.19	silver quality
mucosa of stomach	UBERON:0001199	80.07	gold quality
monocyte	CL:0000576	79.56	gold quality
leukocyte	CL:0000738	79.23	gold quality
omental fat pad	UBERON:0010414	79.12	gold quality
peritoneum	UBERON:0002358	79.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.04	gold quality
visceral pleura	UBERON:0002401	78.92	gold quality
liver	UBERON:0002107	78.82	gold quality
smooth muscle tissue	UBERON:0001135	78.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.12	gold quality
adipose tissue of abdominal region	UBERON:0007808	78.12	gold quality
rectum	UBERON:0001052	77.93	gold quality
gall bladder	UBERON:0002110	77.74	gold quality
left uterine tube	UBERON:0001303	77.59	gold quality
upper lobe of left lung	UBERON:0008952	77.55	gold quality
mucosa of transverse colon	UBERON:0004991	77.34	gold quality
ventricular zone	UBERON:0003053	77.28	gold quality
upper lobe of lung	UBERON:0008948	77.01	gold quality
ascending aorta	UBERON:0001496	76.79	gold quality
granulocyte	CL:0000094	76.77	gold quality
thoracic aorta	UBERON:0001515	76.75	gold quality
metanephros cortex	UBERON:0010533	76.63	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6911	yes	116.00
E-GEOD-135922	yes	37.60
E-ANND-3	yes	18.87
E-MTAB-6386	no	11.93
E-HCAD-13	no	2.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): REL, TP53

miRNA regulators (miRDB)

77 targeting TNFRSF10D, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-1976	99.74	65.48	1127
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-7161-5P	99.68	68.92	1592
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868

Literature-anchored findings (GeneRIF, showing 36)

• 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)
• Enhanced expression of DcR2 promotes peripheral blood eosinophil survival in the airways of allergic asthmatics following segmental antigen challenge. (PMID:12421985)
• 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)
• Respiratory syncytial virus infection strongly up-regulated the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its functional receptors death receptor 4 (DR4) and DR5. (PMID:12915532)
• 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 DcR2 was found to have a truncated and non-functional death domain. (PMID:15538968)
• TRAIL-R4 but not TRAIL-R3 is the decoy receptor which appeared to influence TRAIL sensitivity in breast cancer cells (PMID:15916713)
• CD8+ lymphocytes and NKT lymphocytes, but not CD4+ lymphocytes, express TRAIL-R4 (PMID:15919363)
• Resistance to TRAIL-induced apoptosis in acute myeloid leukemia cells is associated with expression of TRAIL-R4. (PMID:15921376)
• Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis. (PMID:16319225)
• DCR2 was found positive in 81 and 33% normal, 46 and 10% nodular hyperplasia, 74 and 36% PIN tissues, 87 and 89% low-grade carcinomas, and 100 and 93% high-grade carcinomas (PMID:16799475)
• TRAIL-R4-beta is a new splice variant of TRAIL-receptor 4 lacking the cysteine rich domain 1 (PMID:16934748)
• The specificity of DcR1- and DcR2-mediated TRAIL inhibition reveals an additional level of complexity for the regulation of TRAIL signaling. (PMID:16980609)
• CASP8, DCR2, and HIN-1 methylation leads to progression of neuroblastoma (PMID:17545522)
• These data strongly support a recent proposal that a segment at 8p21.3 contains crucial prostate cancer tumor suppressors. (PMID:18460741)
• DCR2-methylated patients showed significantly poorer 5-year event-free survival in the whole neuroblastoma group (43% (PMID:18980997)
• High TRAIL death receptor 4 and decoy receptor 2 expression correlates with significant cell death in pancreatic ductal adenocarcinoma patients. (PMID:18981952)
• Results indicate that disc cells, after herniation, undergo apoptotic cell death via the DR5/TRAIL pathway. (PMID:19730199)
• Higher levels of TRAIL and the TRAIL decoy receptor, TRAIL R4, were expressed by leukocytes in inflamed human periodontal tissues. (PMID:19948942)
• these results demonstrated that hypoxia-inducible factor 1alpha played a crucial role in regulating the transcription of DcR2. (PMID:20018172)
• TRAIL receptor-4 expression profiles on T cells might be important in revelation of rheumatoid arthritis pathogenesis. (PMID:20799941)
• ANT2 shRNA treatment sensitized MCF7, T47 D, and BT474 cells to TRAIL-induced apoptosis by up-regulating the expression of TRAIL death receptors 4 and 5 (DR4 and DR5) and down-regulating the TRAIL decoy receptor 2 (DcR2). (PMID:20875141)
• transcript levels of UCHL1, COL1A2, THBS1 and TNFRSF10D were inversely correlated with promoter methylation (PMID:22028813)
• 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)
• membrane expression more common in endometrioid endometrial cancer than in normal endometrium (PMID:24649804)
• This study identified TNFRSF10D DNA methylation status as an independent prognostic biomarker for relapse-free survival and overall mortality in non-metastatic melanoma patients. (PMID:25003639)
• 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)
• Urinary DcR2 could potentially serve as a novel biomarker for tubulointerstitial injury and may reflect senescence of renal proximal tubular cells in diabetic nephropathy. (PMID:28356293)
• results suggest that CD264 is a surface marker of cellular age for bone marrow-derived mesenchymal stem cells. (PMID:28962588)
• The high-dose hook effect was apparent during ELISA testing of uDcR2 in chronic kidney disease (CKD) patients, yet dilution of the urine samples neutralized this effect. However, the use of a four-fold dilution of urine for uDcR2/cre testing may eliminate the high-dose hook effect and make it possible to effectively monitor the severity of TII in CKD patients. (PMID:29879421)
• data suggest that the determination of intracellular co-expression patterns of TRAIL-R1, TRAIL-R2, and TRAIL-R4 provides an innovative and robust method for risk stratification in breast cancer patients beyond conventional prognostic markers. (PMID:31183506)
• Survival of aging CD264(+) and CD264(-) populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency. (PMID:31612990)
• ELF3 plays an important role in defining TRAIL sensitivity in breast cancer by modulating the expression of decoy receptor 2 (DCR2). (PMID:38787503)

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), TNFRSF10C (ENSG00000173535), TNFRSF4 (ENSG00000186827), TNFRSF18 (ENSG00000186891), TNFRSF25 (ENSG00000215788), TNFRSF6B (ENSG00000243509)

Protein

Protein identifiers

Tumor necrosis factor receptor superfamily member 10D — Q9UBN6 (reviewed: Q9UBN6)

Alternative names: Decoy receptor 2, TNF-related apoptosis-inducing ligand receptor 4, TRAIL receptor with a truncated death domain

All UniProt accessions (1): Q9UBN6

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the cytotoxic ligand TRAIL. Contains a truncated death domain and hence is not capable of inducing apoptosis but protects against TRAIL-mediated apoptosis. Reports are contradictory with regards to its ability to induce the NF-kappa-B pathway. According to PubMed:9382840, it cannot but according to PubMed:9430226, it can induce the NF-kappa-B pathway.

Subcellular location. Membrane.

Tissue specificity. Widely expressed, in particular in fetal kidney, lung and liver, and in adult testis and liver. Also expressed in peripheral blood leukocytes, colon and small intestine, ovary, prostate, thymus, spleen, pancreas, kidney, lung, placenta and heart.

RefSeq proteins (1): NP_003831* (*=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 (25 total): disulfide bond 7, sequence variant 4, repeat 3, region of interest 2, glycosylation site 2, topological domain 2, signal peptide 1, chain 1, compositionally biased region 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBN6-F1	60.71	0.25

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 (7): 83–96, 99–115, 118–131, 121–139, 141–155, 158–172, 162–180

Glycosylation sites (2): 127, 182

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-6803211	TP53 Regulates Transcription of Death Receptors and Ligands
R-HSA-75158	TRAIL signaling

MSigDB gene sets: 112 (showing top): PEREZ_TP63_TARGETS, MODULE_45, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOCC_CELL_SURFACE, chr8p21, LAU_APOPTOSIS_CDKN2A_UP, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, PID_P53_DOWNSTREAM_PATHWAY, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, PEREZ_TP53_AND_TP63_TARGETS, NOJIMA_SFRP2_TARGETS_UP, DOUGLAS_BMI1_TARGETS_UP, MODULE_38, REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL, MODULE_104

GO Biological Process (3): apoptotic process (GO:0006915), signal transduction (GO:0007165), negative regulation of apoptotic process (GO:0043066)

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

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Hemostasis	1
TP53 Regulates Transcription of Cell Death Genes	1
Death Receptor Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
signaling receptor activity	1
protein binding	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFRSF10D	TNFSF10	P50591	988
TNFRSF10D	TNFRSF10B	O14763	742
TNFRSF10D	DOCK5	Q9H7D0	732
TNFRSF10D	CFLAR	O15519	713
TNFRSF10D	CASP10	Q92851	645
TNFRSF10D	TNFRSF10C	O14798	610
TNFRSF10D	CASP8	Q14790	603
TNFRSF10D	FADD	Q13158	581
TNFRSF10D	DCXR	Q7Z4W1	572
TNFRSF10D	TP53	P04637	557
TNFRSF10D	FASLG	P48023	550
TNFRSF10D	CASP7	P55210	509
TNFRSF10D	TNF	P01375	480
TNFRSF10D	TNFRSF6B	O95407	479
TNFRSF10D	CXCL8	P10145	478

IntAct

135 interactions, top by confidence:

A	B	Type	Score
LRRC32	SMPD2	psi-mi:“MI:0914”(association)	0.640
TNFRSF10D	TNFSF10	psi-mi:“MI:0407”(direct interaction)	0.620
TUFM	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
RMDN2	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
ARFIP1	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
CIAO2A	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
GAD2	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
SLC39A7	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
FAM114A1	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
TBRG4	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
RBP1	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
INPP5K	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
HSBP1L1	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
APOL3	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
LAT	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10D	PITPNC1	psi-mi:“MI:0915”(physical association)	0.560
ECPAS	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
TARS2	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
SUCLA2	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
THAP4	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
MIEF1	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
SEMA4G	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
MTERF4	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
PCYT1A	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
SENP2	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10D	POLL	psi-mi:“MI:0915”(physical association)	0.560
NKAPL	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF10D	COL1A1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (47): LRPPRC (Affinity Capture-MS), MYH10 (Affinity Capture-MS), PFAS (Affinity Capture-MS), SF3B3 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TNFRSF10D (Synthetic Lethality), TNFRSF10D (Two-hybrid), TNFRSF10D (Two-hybrid), TNFRSF10D (Two-hybrid), TNFRSF10D (Two-hybrid), TNFRSF10D (Two-hybrid), TNFRSF10D (Two-hybrid), TNFRSF10D (Two-hybrid), TNFRSF10D (Two-hybrid), TNFRSF10D (Two-hybrid)

ESM2 similar proteins: D3ZF92, D5K8A9, O00220, O14763, O15553, O35305, O35714, O75509, P12342, P20333, P22934, P25118, P25119, P26898, P27987, P28908, P50284, P97525, Q2YDG7, Q3U4N7, Q5HZW5, Q5ND28, Q5PQX1, Q60846, Q80WY6, Q86T13, Q86VZ4, Q8BX35, Q8BZW2, Q8CB67, Q8IY92, Q8NC42, Q8TBE3, Q8VCP9, Q8WWF5, Q90VY2, Q921T2, Q96L08, Q9DA48, Q9EPU5

Diamond homologs: O00220, O14763, O14798, P15725, P47741, P83626, Q9QZM4, Q9UBN6, O19131, P19438, P50555, Q80WM9, O00300, O77736, O73559, P0DSV7, P0DSV8, P0DTN0, P22934, P25118, P25943, P29825, P36941, P68636, P68637, Q76ZJ3, A5D7R1, O08712, P20333, P21106, P25119, Q805P6, Q80WY6, Q92956, F5HAM0, P07174, P08138, P18519, P25445, P25942

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TNFRSF10D	down-regulates	TNFSF10	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

994 predictions. Top by Δscore:

Variant	Effect	Δscore
8:23137999:GCTGA:G	acceptor_loss	1.0000
8:23138000:CTGA:C	acceptor_gain	1.0000
8:23138001:TGA:T	acceptor_gain	1.0000
8:23138001:TGAC:T	acceptor_loss	1.0000
8:23138002:GA:G	acceptor_gain	1.0000
8:23138003:ACTGA:A	acceptor_loss	1.0000
8:23138004:C:CC	acceptor_gain	1.0000
8:23138004:CTG:C	acceptor_loss	1.0000
8:23138005:T:G	acceptor_loss	1.0000
8:23138186:A:AC	donor_gain	1.0000
8:23138187:C:CC	donor_gain	1.0000
8:23145056:A:AC	donor_gain	1.0000
8:23145057:C:CC	donor_gain	1.0000
8:23145057:CT:C	donor_gain	1.0000
8:23146955:TCTTA:T	donor_loss	1.0000
8:23146956:CTTA:C	donor_loss	1.0000
8:23146957:TTACC:T	donor_loss	1.0000
8:23146958:TACC:T	donor_loss	1.0000
8:23146959:AC:A	donor_gain	1.0000
8:23146959:ACCC:A	donor_loss	1.0000
8:23146960:CC:C	donor_gain	1.0000
8:23147068:TTGAC:T	acceptor_gain	1.0000
8:23147069:TGAC:T	acceptor_gain	1.0000
8:23147073:C:CC	acceptor_gain	1.0000
8:23147074:T:C	acceptor_loss	1.0000
8:23154888:T:TA	donor_gain	1.0000
8:23163782:TCA:T	donor_loss	1.0000
8:23163783:CA:C	donor_loss	1.0000
8:23163784:A:AC	donor_gain	1.0000
8:23163785:C:CC	donor_gain	1.0000

AlphaMissense

2463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:23147005:G:C	F146L	0.992
8:23147005:G:T	F146L	0.992
8:23147007:A:G	F146L	0.992
8:23147006:A:C	F146C	0.970
8:23147051:C:G	C131S	0.965
8:23147052:A:T	C131S	0.965
8:23148455:C:G	C118S	0.962
8:23148456:A:T	C118S	0.962
8:23147027:C:G	C139S	0.959
8:23147028:A:T	C139S	0.959
8:23147021:C:G	C141S	0.956
8:23147022:A:T	C141S	0.956
8:23154882:C:G	C83S	0.951
8:23154883:A:T	C83S	0.951
8:23147050:A:C	C131W	0.950
8:23148512:C:G	C99S	0.950
8:23148513:A:T	C99S	0.950
8:23148446:C:G	C121S	0.949
8:23148447:A:T	C121S	0.949
8:23148464:C:G	C115S	0.949
8:23148465:A:T	C115S	0.949
8:23145865:C:G	C180S	0.943
8:23145866:A:T	C180S	0.943
8:23146979:C:G	C155S	0.942
8:23146980:A:T	C155S	0.942
8:23147052:A:G	C131R	0.941
8:23148465:A:G	C115R	0.941
8:23154883:A:G	C83R	0.939
8:23147051:C:T	C131Y	0.937
8:23148454:A:C	C118W	0.936

dbSNP variants (sampled 300 via entrez): RS1000048329 (8:23162638 C>T), RS1000183157 (8:23156564 T>C), RS1000583145 (8:23159124 T>C), RS1000636931 (8:23159437 G>A), RS1000736290 (8:23144154 T>C), RS1000858095 (8:23148809 G>A), RS1000892652 (8:23135466 C>A), RS1000935802 (8:23162403 A>G), RS1000967911 (8:23139953 G>A,C), RS1001091492 (8:23148884 T>C), RS1001204426 (8:23154023 G>C,T), RS1001236410 (8:23152947 T>A,C), RS1001534325 (8:23158889 C>T), RS1001581368 (8:23152560 G>C), RS1001632662 (8:23143860 A>G)

Disease associations

OMIM: gene MIM:603614 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000751_1	Attention deficit hyperactivity disorder	3.000000e-06
GCST90002389_171	Lymphocyte percentage of white cells	1.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007993	lymphocyte 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Arsenic	affects methylation, increases expression, affects cotreatment, increases abundance, increases reaction	3
Quercetin	increases expression	3
Cadmium Chloride	increases abundance, increases expression, decreases expression	3
bisphenol A	increases methylation, affects cotreatment, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Arsenic Trioxide	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects expression, increases expression	2
Fluorouracil	increases expression, affects reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Aflatoxin B1	increases expression	2
aristolochic acid I	increases expression	1
picrasidine I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
geldanamycin	increases expression	1
urushiol	decreases expression	1
methylmercuric chloride	increases expression	1
naringenin	affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tributyltin	decreases expression	1
3,4-dichloroaniline	increases expression	1
arsenite	affects expression	1
sulforaphane	increases expression	1
butyraldehyde	increases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
ochratoxin A	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9UJ	Ubigene HEK293 TNFRSF10D KO	Transformed cell line	Female

Clinical trials (associated diseases)

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