TNFRSF8

protein-coding

TNF receptor superfamily member 8, the group of CD molecules|Tumor necrosis factor receptor superfamily

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:

CD30
D1S166E

MANE transcript

NM_001243.5

Inheritance

—

ClinVar variants

U:93B:22

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr1:12,063,303-12,144,207

External References & Databases

Ensembl (ENSG00000120949)

Transcript & Mutation Effects

hg38 • Region Span ~80.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TNFRSF8 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 98

not providedTotal: 9

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001243.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar	5 clinvar	8
missense			88 clinvar	15 clinvar	1 clinvar	104
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	93	16	6	115

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001243.5	RefSeq	NP_001234.3	15	MANE Select
ENST00000263932.7	Ensembl	ENSP00000263932.2	15	MANE Select
NM_001281430.3	RefSeq	NP_001268359.2	12	Standard
ENST00000413146.6	Ensembl	ENSP00000398337.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cytokine-cytokine receptor interaction - Homo sapiens (human)
TNFR2 non-canonical NF-kB pathway
Cytokine Signaling in Immune system
Immune System
TNFs bind their physiological receptors

Biological Process

signal transduction
negative regulation of cell population proliferation
tumor necrosis factor-mediated signaling pathway
positive regulation of tumor necrosis factor biosynthetic process
positive regulation of apoptotic process

Molecular Function

transmembrane signaling receptor activity

Cellular Component

cytoplasm
plasma membrane
integral component of membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263932
Coding exons: 15
Length: 80831
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125747
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.941	320	371	0.863	0.0000233	3795
Missense (PolyPhen)		80	106.88	0.74848		1147
Synonymous	0.299	162	167	0.971	0.0000122	1239
Loss of Function	4.35	6	33.0	0.182	0.00000191	341

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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.;

Recessive Scores

pRec: 0.295

Intolerance Scores

LoFtool: 0.237
RVIS EVS: 0.18
RVIS percentile EVS: 66.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.895

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium