TNFSF8

protein-coding

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

Gene summary

The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for TNFRSF8/CD30, which is a cell surface antigen and a marker for Hodgkin lymphoma and related hematologic malignancies. The engagement of this cytokine expressed on B cell surface plays an inhibitory role in modulating Ig class switch. This cytokine was shown to enhance cell proliferation of some lymphoma cell lines, while to induce cell death and reduce cell proliferation of other lymphoma cell lines. The pleiotropic biologic activities of this cytokine on different CD30+ lymphoma cell lines may play a pathophysiologic role in Hodgkin's and some non-Hodgkin's lymphomas. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

Previous symbols:

CD30LG

MANE transcript

NM_001244.4

Inheritance

—

ClinVar variants

U:23B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr9:114,893,343-114,930,595

External References & Databases

Ensembl (ENSG00000106952)

Transcript & Mutation Effects

hg38 • Region Span ~37.3 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 TNFSF8 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 27

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001244.4. 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						0
missense			23 clinvar	5 clinvar		28
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	23	5	0	28

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001244.4	RefSeq	NP_001235.1	4	MANE Select
ENST00000223795.3	Ensembl	ENSP00000223795.2	4	MANE Select
NM_001252290.1	RefSeq	NP_001239219.1	5	Standard
ENST00000618336.4	Ensembl	ENSP00000484651.1	5	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

apoptotic process
immune response
signal transduction
cell-cell signaling
cell population proliferation

Molecular Function

signaling receptor binding
cytokine activity
tumor necrosis factor receptor binding

Cellular Component

extracellular space
plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000223795
Coding exons: 4
Length: 36695
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125746
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.834	99	125	0.790	0.00000643	1518
Missense (PolyPhen)		24	33.414	0.71827		438
Synonymous	0.674	48	54.3	0.884	0.00000322	464
Loss of Function	2.48	1	9.03	0.111	3.82e-7	116

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
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)	0.0000088	0.0000088	rare
South Asian	0.000035	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cytokine that binds to TNFRSF8/CD30. Induces proliferation of T-cells.;

Recessive Scores

pRec: 0.156

Intolerance Scores

LoFtool: 0.0787
RVIS EVS: -0.05
RVIS percentile EVS: 49.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.674

Gene Damage Prediction

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