TNFRSF17

Chr 16

TNF receptor superfamily member 17

Also known as: BCM, BCMA, CD269, TNFRSF13A

NCBI Gene: 608ENSG00000048462UniProt: Q02223OMIM: 109545

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.88
Clinical Summary— TNFRSF17
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 VUS of 28 total submissions
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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 OE?1.27 (0.72–1.88)
0≤0.351.4
Missense OE?1.34 (1.17–1.54)
0≤0.61.4
Synonymous OE?1.22
0≤1.21.6
LoF obs/exp: 8 / 6.3Missense obs/exp: 143 / 106.8Syn Z: -1.12

This gene — mechanism propensity

DN
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

28 submitted variants in ClinVar

ClinVar

Classification Summary

VUS26
Benign1
26
VUS
1
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
26
0
0
26
Likely Benign
0
0
0
0
0
Benign
0
1
0
0
1
Total0270027

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap TNFRSF17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

TNFRSF17 · protein map & ClinVar variants

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

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