TNFRSF8

Summary

TNFRSF8 (TNF receptor superfamily member 8, HGNC:11923) is a protein-coding gene on chromosome 1p36.22, encoding Tumor necrosis factor receptor superfamily member 8 (P28908). Receptor for TNFSF8/CD30L.

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, and mediate the signal transduction that leads to the activation of NF-kappaB. This receptor is a positive regulator of apoptosis, and also has been shown to limit the proliferative potential of autoreactive CD8 effector T cells and protect the body against autoimmunity. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.

Source: NCBI Gene 943 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 116 total
• Druggable target: yes
• MANE Select transcript: NM_001243

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11923
Approved symbol	TNFRSF8
Name	TNF receptor superfamily member 8
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	KI-1
Ensembl gene	ENSG00000120949
Ensembl biotype	protein_coding
OMIM	153243
Entrez	943

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000263932, ENST00000413146, ENST00000417814, ENST00000479933, ENST00000514649

RefSeq mRNA: 2 — MANE Select: NM_001243 NM_001243, NM_001281430

CCDS: CCDS144, CCDS59989

Canonical transcript exons

ENST00000263932 — 15 exons

Exon	Start	End
ENSE00001690860	12084464	12084551
ENSE00002179428	12063303	12063661
ENSE00003464618	12135588	12135613
ENSE00003467814	12104379	12104531
ENSE00003490379	12123284	12123377
ENSE00003502329	12111898	12112014
ENSE00003521024	12123715	12123827
ENSE00003561792	12115577	12115729
ENSE00003563250	12110041	12110204
ENSE00003597469	12142287	12144207
ENSE00003598326	12126183	12126236
ENSE00003601080	12097101	12097217
ENSE00003615042	12138229	12138436
ENSE00003616674	12125951	12126052
ENSE00003645768	12109566	12109656

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 83.22.

FANTOM5 (CAGE): breadth broad, TPM avg 7.2425 / max 361.1604, expressed in 424 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
678	1.8094	202
682	1.3445	81
680	1.2163	190
681	0.8311	140
697	0.3166	78
684	0.2162	55
677	0.1877	95
676	0.1851	63
679	0.1836	105
695	0.1560	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	83.22	gold quality
monocyte	CL:0000576	83.15	gold quality
leukocyte	CL:0000738	82.76	gold quality
mononuclear cell	CL:0000842	82.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.37	gold quality
blood	UBERON:0000178	76.11	gold quality
pancreatic ductal cell	CL:0002079	74.59	gold quality
decidua	UBERON:0002450	73.17	silver quality
omental fat pad	UBERON:0010414	71.74	gold quality
peritoneum	UBERON:0002358	71.70	gold quality
adipose tissue of abdominal region	UBERON:0007808	71.12	gold quality
subcutaneous adipose tissue	UBERON:0002190	70.85	gold quality
periodontal ligament	UBERON:0008266	67.98	silver quality
buccal mucosa cell	CL:0002336	67.49	gold quality
adipose tissue	UBERON:0001013	67.43	gold quality
connective tissue	UBERON:0002384	66.83	gold quality
vermiform appendix	UBERON:0001154	66.78	gold quality
right atrium auricular region	UBERON:0006631	66.00	gold quality
parotid gland	UBERON:0001831	64.89	gold quality
triceps brachii	UBERON:0001509	64.76	gold quality
cardiac atrium	UBERON:0002081	64.61	gold quality
tendon of biceps brachii	UBERON:0008188	63.88	gold quality
putamen	UBERON:0001874	63.58	gold quality
nucleus accumbens	UBERON:0001882	63.51	gold quality
gluteal muscle	UBERON:0002000	63.45	gold quality
apex of heart	UBERON:0002098	63.25	gold quality
caudate nucleus	UBERON:0001873	62.80	gold quality
caecum	UBERON:0001153	62.61	gold quality
lymph node	UBERON:0000029	62.42	gold quality
germinal epithelium of ovary	UBERON:0001304	62.03	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ETS1, JUN, JUNB, MYC, PITX2, SATB1, SP1, SP3, STAT1, STAT6, YY1

miRNA regulators (miRDB)

38 targeting TNFRSF8, 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-6748-5P	100.00	65.81	1057
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656

Literature-anchored findings (GeneRIF, showing 40)

• expression in T cells up-regulated by CD30L (PMID:11728464)
• Differential expression of CD30 and p80 between peripheral blood and bone marrow lymphoma cells is a property of the small cell variant of anaplastic large cell lymphoma. (PMID:11891807)
• constitutive signaling by CD30 drives NF-kappaB activation in Hodgkin-Reed-Sternberg cells (PMID:11971184)
• Single-cell analysis of CD30+ cells in lymphomatoid papulosis demonstrates a common clonal T-cell origin. (PMID:12091351)
• CD30, but not 4-1BB or OX-40, is preferentially induced by alloantigen, suggesting that CD30 may be important in human alloimmune responses (PMID:12165500)
• REVIEW: CD30-mediated signal transduction pathways and possible roles in Hodgkins disease and anaplastic large cell lymphoma (PMID:12389614)
• only in a subset of both benign and malignant thyroid nodules the interleukin-6/interleukin-6 receptor signal could be induced by the CD30 ligand/CD30 (PMID:12553555)
• Results suggest that the N- and C-termini of the extracellular portion of CD30 are in close vicinity of each other, suggesting a flower-like structure for the membrane-bound homotrimeric CD30 molecule. (PMID:12557237)
• REVIEW: the biological link between 2 characteristic features of H-RS cells: CD30 overexpression and constitutive NF-kappaB activation (PMID:12568298)
• REVIEW: role of CD30 in determining the activity of T cells toward synthesis of cytokines and involvement in reactions of Th2 characteristics. (PMID:12799531)
• Data suggest that overexpression and binding of JunB to the AP-1 site may relieve the repression of the core promoter by CD30 in Hodgkin-Redd Sternberg cells, which provide one basis for the constitutive overexpression of CD30 in Hodgkin’s lymphoma. (PMID:12875982)
• the anti-inflammatory activity of IL-4-producing CD30+ CD4+ T cells in rheumatoid arthritis may be limited in the synovium due to a poor induction of surface CD30 and a susceptibility to CD30-mediated cell death. (PMID:14726963)
• Increased levels of CD30 is associted with ineffective antitumor immunity in Hodgkin’s disease (PMID:15026356)
• CD30 shedding is stimulated by an elevated local availability of cysteine-rich domain 2 or 5, possibly by forming a docking station for the releasing enzyme through substrate aggregation. (PMID:15033921)
• CD30-regulated expression of cIAP1 & cIAP2 is mediated by NFkappaB & correlates with protection from etoposide-induced apoptosis. CD30-induced signaling may have a major impact on the clinical outcome of patients with anaplastic large cell lymphoma cells. (PMID:15050749)
• CD30 can act as both a positive and negative growth factor depending on cell type (PMID:15175022)
• CD30 activation plays a role in eosinophil apoptosis. (PMID:15265955)
• results suggest that CD30-mediated apoptosis is not a common feature in this cell type and that p38 MAP kinase is involved in CD30-mediated singal transduction. (PMID:15291361)
• Immunity to CD30 could play a role in Marek disease lymphoma regression. (PMID:15356338)
• The results showed that: (1) epithelial cells in the developing intestinal crypts express the CD30 (Ki-1) antigen; (2) CD30 expression in these epithelial cells is higher in cases of hormonal administration than in normal gestation. (PMID:15644135)
• CD30 transformed cells trigger the noncanonical NF-kappaB activation pathway, and suggest that deregulated CD30 signaling contributes to the neoplastic features of Hodgkin Reed Sternberg cells. (PMID:15782119)
• Elevated CD30 expression is considered one of the causes of constitutive NF-kappaB activation in adult T-cell Leukemia (ATL) cells, and may be involved in ATL development. (PMID:15876358)
• Pretransplant soluble CD30 is a more accurate predictor of acute rejection when compared with panel reactive antibodiees in kidney transplantation. (PMID:15880060)
• This marker provides a risk factor for chronic kidney transplant rejection independent of classical immunological risk factors and may be down-regulated using Tacrolimus treatment. (PMID:15919463)
• Presence of CD30 T cells correlated with preservation of graft function following lung transplantation. (PMID:15964393)
• CD30 is a costimulatory molecule and marker of a regulatory subpopulation of DCs which induces and modulates immune cells involved in the maintenance of the balance between TH1/TH2 immune responses and tolerance. (PMID:15990453)
• High pre-transplant levels of soluble CD30 are associated with antibody-mediated rejection of Kidney Transplantation (PMID:15996240)
• Expression patterns of the tumor marker CD30, which is a cell surface antigen expressed Hodgkin’s lymphoma in mice. (PMID:16108827)
• (p52)2/Bcl-3P ternary complex, which is specifically induced in CD30-stimulated anaplasstic larage cell lymphoma, can modulate expression of apoptosis-related genes regulated by NF-kappaB. (PMID:16108830)
• CD30 antigen is of importance in cell development, and proliferation and is also pathway-related to terminal differentiation in many fetal tissues and organs. (PMID:16244703)
• CD30-L/CD30 and IL-6/IL-6R systems could play a major role in the pathogenesis of Graves’disease (GD), but the expression of CD30L/CD30 and IL-6/IL-6R in Hashimoto’s thyroiditis (HT) suggests that Th2 mechanisms are involved in tissue damage. (PMID:16372246)
• Good HLA matching seems to be effective in neutralizing the negative effect of a high pretransplant serum CD30. (PMID:16378078)
• Soluble CD30 could be an important biomarker for an immune system environment conducive to B cell hyperactivation and the development of AIDS-associated B cell lymphoma (PMID:16651853)
• Findings provide additional evidence that CD30 expression is not restricted to neoplasms of lymphoid origin. (PMID:16722935)
• elevated soluble CD30 and neopterin predict graft deterioration by chronic allograft nephropathy (PMID:16771810)
• Patients positive for sCD30 contents are at high risk for the development of donor-specific HLA antibodies and acute rejection after kidney transplantation. (PMID:16842522)
• Measurement of plasma CD30 is a useful procedure for the recognition of rejection in its earliest stages. (PMID:16980071)
• Significant differences were found between systemic lupus erythematosus patients and controls (p=0.0001). (PMID:17103120)
• Increase of CD30 expression is associated with advancement of Hodgkin’s disease. ’ (PMID:17106517)
• Neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients. (PMID:17175343)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdr	ENSDARG00000004392
danio_rerio	tnfrsfa	ENSDARG00000004451
danio_rerio	cd40	ENSDARG00000054968
danio_rerio	tnfrsf1b	ENSDARG00000070165
danio_rerio	tnfrsf11a	ENSDARG00000087804
mus_musculus	Tnfrsf8	ENSMUSG00000028602
rattus_norvegicus	Tnfrsf8	ENSRNOG00000016782

Paralogs (21): FAS (ENSG00000026103), TNFRSF1B (ENSG00000028137), TNFRSF9 (ENSG00000049249), RELT (ENSG00000054967), NGFR (ENSG00000064300), TNFRSF1A (ENSG00000067182), CD40 (ENSG00000101017), TNFRSF10A (ENSG00000104689), LTBR (ENSG00000111321), TNFRSF10B (ENSG00000120889), CD27 (ENSG00000139193), TNFRSF11A (ENSG00000141655), TNFRSF21 (ENSG00000146072), TNFRSF14 (ENSG00000157873), TNFRSF11B (ENSG00000164761), TNFRSF10D (ENSG00000173530), TNFRSF10C (ENSG00000173535), TNFRSF4 (ENSG00000186827), TNFRSF18 (ENSG00000186891), TNFRSF25 (ENSG00000215788), TNFRSF6B (ENSG00000243509)

Protein

Protein identifiers

Tumor necrosis factor receptor superfamily member 8 — P28908 (reviewed: P28908)

Alternative names: CD30L receptor, Ki-1 antigen, Lymphocyte activation antigen CD30

All UniProt accessions (2): D6RAG8, P28908

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for TNFSF8/CD30L. May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa-B.

Subunit / interactions. Interacts with TRAF1, TRAF2, TRAF3 and TRAF5.

Subcellular location. Cell membrane Cytoplasm.

Tissue specificity. Detected in alveolar macrophages (at protein level).

Post-translational modifications. Phosphorylated on serine and tyrosine residues. Isoform 2 is constitutively phosphorylated.

Miscellaneous. Most specific Hodgkin disease associated antigen.

Similarity. Belongs to the TNFR8 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P28908-1	1, Long	yes
P28908-2	2, Cytoplasmic, Short, C30V
P28908-3	3

RefSeq proteins (2): NP_001234, NP_001268359 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR020416	TNFR_8	Family
IPR034002	TNFRSF8_N	Domain
IPR052862	TNFR_superfamily_member_8	Family

Pfam: PF00020

UniProt features (49 total): disulfide bond 14, repeat 6, sequence variant 6, region of interest 5, compositionally biased region 4, glycosylation site 4, splice variant 3, topological domain 2, modified residue 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1D01	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28908-F1	61.90	0.22

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 (2): 438, 452

Disulfide bonds (14): 29–44, 45–58, 48–65, 69–81, 84–98, 87–106, 108–122, 131–149, 233–240, 244–256, 259–273, 262–281, 283–297, 289–300

Glycosylation sites (4): 32, 101, 276, 336

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 149 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, SA_MMP_CYTOKINE_CONNECTION, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP, GOBP_POSITIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_SUPERFAMILY_CYTOKINE_PRODUCTION, MUELLER_PLURINET, CATTTCA_MIR203, KLEIN_PRIMARY_EFFUSION_LYMPHOMA_UP, GOBP_CYTOKINE_PRODUCTION, MODULE_99, TGACATY_UNKNOWN, MARZEC_IL2_SIGNALING_UP, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, PEART_HDAC_PROLIFERATION_CLUSTER_DN

GO Biological Process (6): signal transduction (GO:0007165), negative regulation of cell population proliferation (GO:0008285), positive regulation of TRAIL production (GO:0032759), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of apoptotic process (GO:0043065), cellular response to mechanical stimulus (GO:0071260)

GO Molecular Function (3): protease binding (GO:0002020), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

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
cellular anatomical structure	3
positive regulation of tumor necrosis factor superfamily cytokine production	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
TRAIL production	1
regulation of TRAIL production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
enzyme binding	1
signaling receptor activity	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

1770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFRSF8	TNFSF8	P32971	999
TNFRSF8	FCGR3A	P08637	990
TNFRSF8	FCGR3B	O75015	986
TNFRSF8	CD40	P25942	950
TNFRSF8	TRAF5	O00463	941
TNFRSF8	TNFRSF4	P43489	935
TNFRSF8	CD27	P26842	934
TNFRSF8	TNFSF4	P23510	897
TNFRSF8	TRAF3	Q13114	887
TNFRSF8	FUT4	P22083	872
TNFRSF8	CD70	P32970	871
TNFRSF8	TNF	P01375	853
TNFRSF8	TNFRSF14	Q92956	850
TNFRSF8	CD40LG	P29965	846
TNFRSF8	CD5	P06127	840

IntAct

11 interactions, top by confidence:

A	B	Type	Score
TNFSF8	TNFRSF8	psi-mi:“MI:0915”(physical association)	0.610
TNFSF8	TNFRSF8	psi-mi:“MI:0407”(direct interaction)	0.610
TNFRSF8	DAPK3	psi-mi:“MI:0914”(association)	0.530
TNFRSF8	TNFRSF8	psi-mi:“MI:0407”(direct interaction)	0.440
TNFRSF8	Traf1	psi-mi:“MI:0915”(physical association)	0.400
Traf2	TNFRSF8	psi-mi:“MI:0915”(physical association)	0.400
DLL1	TNFRSF8	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF8	DSCAM	psi-mi:“MI:0915”(physical association)	0.400
BCL6	CACNA1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (67): NAA25 (Affinity Capture-MS), CCDC112 (Affinity Capture-MS), NAA20 (Affinity Capture-MS), CEP57 (Affinity Capture-MS), TRAF3 (Affinity Capture-MS), DPY19L1 (Affinity Capture-MS), DAPK3 (Affinity Capture-MS), TRAF1 (Affinity Capture-MS), SPATS2 (Affinity Capture-MS), BLOC1S1 (Affinity Capture-MS), TRAF2 (Affinity Capture-MS), EXOC1 (Affinity Capture-MS), ATP6V1D (Affinity Capture-MS), GOLPH3L (Affinity Capture-MS), RACGAP1 (Affinity Capture-MS)

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: A5D7R1, D3ZF92, O00300, O08712, O08727, O35305, O73559, O75509, O95407, P0DSV7, P0DSV8, P25119, P25942, P25943, P27512, P28908, P83626, Q28203, Q3LRP1, Q3ZTK5, Q7YRL5, Q8SQ34, Q9EPU5, Q9Y6Q6, P97525, Q60846

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	17
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2690 predictions. Top by Δscore:

Variant	Effect	Δscore
1:12063662:G:GA	donor_loss	1.0000
1:12063663:T:G	donor_loss	1.0000
1:12097215:GAG:G	donor_gain	1.0000
1:12097217:GGTAA:G	donor_loss	1.0000
1:12097218:G:GG	donor_gain	1.0000
1:12097218:GTA:G	donor_loss	1.0000
1:12097219:T:G	donor_loss	1.0000
1:12111896:A:AG	acceptor_gain	1.0000
1:12111897:G:GA	acceptor_gain	1.0000
1:12111897:G:GT	acceptor_loss	1.0000
1:12111897:GGT:G	acceptor_gain	1.0000
1:12111897:GGTC:G	acceptor_gain	1.0000
1:12111897:GGTCT:G	acceptor_gain	1.0000
1:12112012:GAG:G	donor_gain	1.0000
1:12112014:GGTA:G	donor_loss	1.0000
1:12112015:G:GG	donor_gain	1.0000
1:12112015:GTAAG:G	donor_loss	1.0000
1:12112016:T:A	donor_loss	1.0000
1:12115575:A:AG	acceptor_gain	1.0000
1:12115576:G:GG	acceptor_gain	1.0000
1:12115728:GG:G	donor_gain	1.0000
1:12115729:GG:G	donor_gain	1.0000
1:12115729:GGTAA:G	donor_loss	1.0000
1:12115731:T:G	donor_loss	1.0000
1:12123825:CAGGT:C	donor_loss	1.0000
1:12123826:AGGTA:A	donor_loss	1.0000
1:12123828:G:GC	donor_loss	1.0000
1:12123829:T:G	donor_loss	1.0000
1:12126048:GCAGA:G	donor_gain	1.0000
1:12126051:GA:G	donor_gain	1.0000

AlphaMissense

3846 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:12142299:T:C	I519T	0.995
1:12142299:T:A	I519N	0.994
1:12142299:T:G	I519S	0.994
1:12142293:T:C	I517T	0.992
1:12142293:T:G	I517S	0.991
1:12115630:T:A	C283S	0.984
1:12115631:G:C	C283S	0.984
1:12142320:T:A	I526N	0.984
1:12138434:T:G	I514S	0.983
1:12142303:G:A	M520I	0.983
1:12142303:G:C	M520I	0.983
1:12142303:G:T	M520I	0.983
1:12104447:T:C	F113L	0.982
1:12104449:C:A	F113L	0.982
1:12104449:C:G	F113L	0.982
1:12104483:T:A	C125S	0.981
1:12104484:G:C	C125S	0.981
1:12104432:T:A	C108S	0.979
1:12104433:G:C	C108S	0.979
1:12115681:T:A	C300S	0.979
1:12115682:G:C	C300S	0.979
1:12142295:T:G	Y518D	0.979
1:12142317:T:A	V525E	0.979
1:12104485:C:G	C125W	0.978
1:12142307:G:C	A522P	0.978
1:12115624:T:A	C281S	0.976
1:12115625:G:C	C281S	0.976
1:12115630:T:C	C283R	0.976
1:12142320:T:G	I526S	0.976
1:12142325:G:T	G528W	0.976

dbSNP variants (sampled 300 via entrez): RS1000017817 (1:12091497 T>A), RS1000023885 (1:12117563 C>T), RS1000080422 (1:12132796 C>T), RS1000092118 (1:12073266 A>G), RS1000130287 (1:12112069 G>A,T), RS1000175618 (1:12084529 G>A), RS1000190655 (1:12082831 C>T), RS1000198284 (1:12122195 A>C), RS1000202710 (1:12113495 G>A), RS1000204879 (1:12088828 T>C), RS1000305754 (1:12062204 T>A), RS1000306937 (1:12127470 A>C), RS1000325095 (1:12067188 C>T), RS1000327415 (1:12129022 A>G), RS1000339314 (1:12077600 G>A,C,T)

Disease associations

OMIM: gene MIM:153243 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST004600_57	Eosinophil percentage of white cells	2.000000e-12
GCST004606_177	Eosinophil count	9.000000e-11
GCST004617_51	Eosinophil percentage of granulocytes	9.000000e-12
GCST004623_144	Neutrophil percentage of granulocytes	5.000000e-11
GCST004624_203	Sum eosinophil basophil counts	1.000000e-09
GCST004863_39	Mosquito bite size	4.000000e-08
GCST004923_1	Tuberculosis	1.000000e-11
GCST009798_30	Asthma	8.000000e-13
GCST010042_94	Asthma	4.000000e-12
GCST010043_79	Asthma	2.000000e-09
GCST011353_31	Serum alkaline phosphatase levels	7.000000e-09
GCST90002381_563	Eosinophil count	1.000000e-21
GCST90002382_58	Eosinophil percentage of white cells	5.000000e-10
GCST90002382_59	Eosinophil percentage of white cells	4.000000e-28
GCST90014325_28	Asthma	2.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0008378	mosquito bite reaction size measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364161 (SINGLE PROTEIN)

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

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
AFM13	Binding	8.03	pKd

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases reaction, affects cotreatment, decreases expression, affects methylation, increases methylation (+1 more)	3
entinostat	increases expression, affects cotreatment	2
Catechin	affects cotreatment, decreases expression, decreases reaction	2
Valproic Acid	affects expression, increases methylation	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
hydroxyhydroquinone	decreases expression, decreases reaction	1
arsenite	increases methylation	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	decreases reaction, affects cotreatment, decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
4-aminobenzhydrazide	decreases reaction, decreases expression	1
usnic acid	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
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Aripiprazole	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Ethanol	increases expression, increases reaction	1
Arsenic	increases expression	1
Calcitriol	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Cycloheximide	decreases reaction, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Dust	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Menthol	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Oxygen	affects cotreatment, decreases secretion	1

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2J4	Abcam HeLa TNFRSF8 KO	Cancer cell line	Female
CVCL_B8R6	Abcam HCT 116 TNFRSF8 KO	Cancer cell line	Male
CVCL_B9TK	Abcam A-549 TNFRSF8 KO	Cancer cell line	Male
CVCL_D2HI	Abcam MCF-7 TNFRSF8 KO	Cancer cell line	Female
CVCL_E6S6	Genomeditech CHO-K1 H_TNFRSF8(CD30)	Spontaneously immortalized cell line	Female
CVCL_E8JF	HT1080 human CD30	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer