TNFRSF17

Chr 16

TNF receptor superfamily member 17

Also known as: BCM, BCMA, CD269, TNFRSF13A

NCBI Gene: 608 ENSG00000048462 UniProt: Q02223 OMIM: 109545

TNFRSF17 encodes a TNF receptor superfamily member that binds BAFF and APRIL ligands to promote B-cell survival and regulate humoral immunity through NF-kappaB and JNK activation. Mutations cause immunodeficiency with defective B-cell function, resulting in recurrent infections and impaired antibody responses. This gene shows very low constraint against loss-of-function variants (pLI near 0, LOEUF 1.88), suggesting tolerance to complete loss of function.

OMIM ResearchSummary from RefSeq, UniProt

MultiplemechanismLOEUF 1.88

Clinical Summary— TNFRSF17

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

1.88LOEUF

pLI 0.000

Z-score -0.63

OE 1.27 (0.72–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

-1.24Z-score

OE missense 1.34 (1.17–1.54)

143 obs / 106.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios

LoF OE1.27 (0.72–1.88)

0≤0.351.4

Missense OE1.34 (1.17–1.54)

0≤0.61.4

Synonymous OE1.22

0≤1.21.6

LoF obs/exp: 8 / 6.3Missense obs/exp: 143 / 106.8Syn Z: -1.12

0.7036th %ile

GOF

0.76top 25%

LOF

0.3164th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction 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

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TNFRSF17 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Breast Cancer Early Stage Breast Cancer (Stage 1-3)Prehabilitation

Multimodal Prehabilitation Program That Combines Physical Exercise, Psychological Intervention and Nutritional Support to Improve the Response to Neoadjuvant Chemoterhapy in Early Breast Cancer Patients

RECRUITING

NCT07107594Phase NAHospital Clinic of BarcelonaStarted 2025-01-14

Multimodal prehabilitation

Leukemia, Plasma Cell

Study to Evaluate the Safety and Efficacy of ARI0002h, for the Initial Treatment of Patients With Primary Plasma Cell Leukaemia

NOT YET RECRUITING

NCT06830733Phase PHASE2Fundacion Clinic per a la Recerca BiomédicaStarted 2025-04

ARI0002h

Clinical Literature

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Landmark / reviewRecent case evidence

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