TNFRSF8

Chr 1

TNF receptor superfamily member 8

Also known as: CD30, D1S166E, Ki-1

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]

OMIMResearchGenerating clinical summary…
GOFmechanismLOEUF 0.36
Clinical SummaryTNFRSF8
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.
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ClinVar Variants
85 VUS of 118 total submissions
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Clinical Trials
9 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.36LOEUF
pLI 0.864
Z-score 4.35
OE 0.18 (0.100.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.94Z-score
OE missense 0.86 (0.790.95)
320 obs / 371.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.18 (0.100.36)
00.351.4
Missense OE?0.86 (0.790.95)
00.61.4
Synonymous OE?0.97
01.21.6
LoF obs/exp: 6 / 33.0Missense obs/exp: 320 / 371.0Syn Z: 0.30

This gene — mechanism propensity

DN
0.5280th %ile
GOF
0.73top 25%
LOF
0.4136th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

118 submitted variants in ClinVar

Classification Summary

VUS85
Likely Benign17
Benign6
85
VUS
17
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
85
0
0
85
Likely Benign
0
15
1
1
17
Benign
0
1
0
5
6
Total010116108

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

38 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap TNFRSF8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

TNFRSF8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Recurrent Classic Hodgkin LymphomaRefractory Classic Hodgkin Lymphoma

Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

ACTIVE NOT RECRUITING
NCT01896999Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2014-03-07
Biopsy ProcedureBiospecimen CollectionBrentuximab Vedotin
LymphomaLymphoma, Non-HodgkinImmune System Diseases

Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL

ACTIVE NOT RECRUITING
NCT02690545Phase PHASE1, PHASE2UNC Lineberger Comprehensive Cancer CenterStarted 2016-08-26
ATLCAR.CD30 cells
LymphomaImmune System DiseasesImmunoproliferative Disorders

Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL

ACTIVE NOT RECRUITING
NCT03602157Phase PHASE1UNC Lineberger Comprehensive Cancer CenterStarted 2018-10-29
ATLCAR.CD30.CCR4 cellsALTCAR.CD30 cellsBendamustine
Head and Neck Cancers

The Role of Dietary Fiber in Mitigating Sarcopenia Risk in Head and Neck Cancer

RECRUITING
NCT07622914University of OklahomaStarted 2025-10-31
CD30-Positive Diffuse Large B-Cell LymphomaAnaplastic Large Cell Lymphoma, T Cell and Null Cell TypeAnaplastic Large Cell Lymphoma, ALK-Positive

Constitutive IL7R (C7R) Modified Banked Allogeneic CD30.CAR EBVSTS for CD30-Positive Lymphomas

RECRUITING
NCT06176690Phase PHASE1Baylor College of MedicineStarted 2025-10-27
C7R.CD30.CAR-EBVST cells
LymphomaB Cell LymphomaCD30+ Peripheral T-cell Lymphoma

CD30 CAR-T in the Treatment of CD30 Positive Lymphoma

NOT YET RECRUITING
NCT07048353Phase EARLY_PHASE1Shandong Qilu Cell Therapy Engineering Technology Co., LtdStarted 2025-07-28
chimeric antigen receptor gene modified T cells
Lymphoma, B-Cell

CD30 CAR-T in the Treatment of CD30 Positive Relapsed/Refractory Lymphoma

RECRUITING
NCT06850285Phase NAShanxi Bethune HospitalStarted 2025-09-05
chimeric antigen receptor gene modified T cells
Hodgkin DiseaseLymphomaLymphoma, Non-Hodgkin

Administration of T Lymphocytes for Prevention of Relapse of Lymphomas

ACTIVE NOT RECRUITING
NCT02663297Phase PHASE1UNC Lineberger Comprehensive Cancer CenterStarted 2016-06-07
ATLCAR.CD30 cells
Cardiovascular DiseaseFrailty

Investigating the Combined Effects of Protein, Blueberries, and Exercise on Cardiovascular Health and Frailty in Older Nova Scotians

RECRUITING
NCT06693271Phase NANova Scotia Health AuthorityStarted 2025-12-15
intervention of protein, blueberriesExercise training