TNFRSF8

Chr 1

TNF receptor superfamily member 8

Also known as: CD30, D1S166E, Ki-1

NCBI Gene: 943 ENSG00000120949 UniProt: P28908 OMIM: 153243

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.36

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.36LOEUF

pLI 0.864

Z-score 4.35

OE 0.18 (0.10–0.36)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.94Z-score

OE missense 0.86 (0.79–0.95)

320 obs / 371.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.10–0.36)

0≤0.351.4

Missense OE?0.86 (0.79–0.95)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 6 / 33.0Missense obs/exp: 320 / 371.0Syn Z: 0.30

Background carrier burden — how many people carry a rare variant somewhere in TNFRSF8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 70

767 rare PASS variants

Rare truncating (LoF)

1 in 5,400

64 rare PASS variants

Rare synonymous (reference)

1 in 100

375 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TNFRSF8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 95	1 in 5,600
South Asian	~43k	1 in 62	1 in 1,000
Remaining (unassigned)	~30k	1 in 54	1 in 950
European (Finnish)	~27k	1 in 170	≈ 1 in 7,900
Admixed American	~22k	1 in 48	≈ 1 in 11,000
African / African American	~21k	1 in 71	≈ 1 in 16,000
East Asian	~20k	1 in 54	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 240	none seen
Middle Eastern	~2,884	1 in 63	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 15 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 15.? see exons ↓