TNFRSF13B

Chr 17ADAR

TNF receptor superfamily member 13B

Also known as: CD267, CVID, CVID2, IGAD2, RYZN, TACI, TNFRSF14B

NCBI Gene: 23495ENSG00000240505UniProt: O14836

The protein encoded by this gene is a lymphocyte-specific member of the tumor necrosis factor (TNF) receptor superfamily. It interacts with calcium-modulator and cyclophilin ligand (CAML). The protein induces activation of the transcription factors NFAT, AP1, and NF-kappa-B and plays a crucial role in humoral immunity by interacting with a TNF ligand. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Immunodeficiency, common variable, 2MIM #240500
ADAR
Immunoglobulin A deficiency 2MIM #609529
494
ClinVar variants
138
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TNFRSF13B
🧬
Gene-Disease Validity (ClinGen)
immunodeficiency, common variable, 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
138 Pathogenic / Likely Pathogenic· 207 VUS of 494 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.96LOEUF
pLI 0.000
Z-score -2.17
OE 1.73 (1.14–1.96)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.20Z-score
OE missense 1.26 (1.13–1.41)
215 obs / 170.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.73 (1.14–1.96)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.26 (1.13–1.41)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 18 / 10.4Missense obs/exp: 215 / 170.8Syn Z: -0.99

ClinVar Variant Classifications

494 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic127
Likely Pathogenic11
VUS207
Likely Benign110
Benign18
Conflicting21
127
Pathogenic
11
Likely Pathogenic
207
VUS
110
Likely Benign
18
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
0
112
0
127
Likely Pathogenic
6
1
4
0
11
VUS
12
168
23
4
207
Likely Benign
0
7
29
74
110
Benign
0
1
12
5
18
Conflicting
—21
Total3317718083494

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

View in ClinVar →

Protein Context — Lollipop Plot

TNFRSF13B · protein map & ClinVar variants

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

Gene2Phenotype Curations

TNFRSF13B-related immunodeficiency, common variable

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Immunodeficiency, common variable, 2

MIM #240500

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Immunoglobulin A deficiency 2

MIM #609529

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients.
Stranneheim H et al.·Genome Med
2021Cohort
Clinical Associations of Biallelic and Monoallelic TNFRSF13B Variants in Italian Primary Antibody Deficiency Syndromes.
Pulvirenti F et al.·J Immunol Res
2016
Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes.
Salzer U et al.·Blood
2009
Deciphering the genetics and mechanisms of predisposition to multiple myeloma.
Went M et al.·Nat Commun
2024Functional
Innate Mechanisms in Selective IgA Deficiency.
Zhang J et al.·Front Immunol
2021Review
Role of Skewed X-Chromosome Inactivation in Common Variable Immunodeficiency.
Garcia-Prat M et al.·J Clin Immunol
2024
TNFRSF13B in B cell responses to organ transplantation.
Cascalho M et al.·Hum Immunol
2023
TACI deficiency - a complex system out of balance.
Salzer U et al.·Curr Opin Immunol
2021Review
TNFRSF13B polymorphisms counter microbial adaptation to enteric IgA.
Platt JL et al.·JCI Insight
2021
TNFRSF13B/TACI Mutations in Patients with Chronic Rhinosinusitis with Nasal Polyps.
Tsiouma GK et al.·Am J Rhinol Allergy
2023Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools