TNFRSF13C

Chr 22AR

TNF receptor superfamily member 13C

NCBI Gene: 115650ENSG00000159958UniProt: Q96RJ3

B-cell receptor specific for TNFSF13B/TALL1/BAFF/BLyS. Promotes the survival of mature B-cells and the B-cell response

Primary Disease Associations & Inheritance

Immunodeficiency, common variable, 4MIM #613494
AR
241
ClinVar variants
22
Pathogenic / LP
0.27
pLI score
2
Active trials
Clinical Summary— TNFRSF13C
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 126 VUS of 241 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

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.
1.27LOEUF
pLI 0.270
Z-score 1.28
OE 0.27 (0.10–1.27)
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.
0.64Z-score
OE missense 0.80 (0.65–0.98)
65 obs / 81.4 exp
Tolerant

Mild missense constraint

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.0.27 (0.10–1.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.65–0.98)
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.1.42
0≤1.21.6
LoF obs/exp: 1 / 3.6Missense obs/exp: 65 / 81.4Syn Z: -2.13

ClinVar Variant Classifications

241 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS126
Likely Benign69
Benign9
Conflicting14
20
Pathogenic
2
Likely Pathogenic
126
VUS
69
Likely Benign
9
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
1
1
0
2
VUS
2
99
24
1
126
Likely Benign
0
0
16
53
69
Benign
0
1
7
1
9
Conflicting
—14
Total21016855240

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

View in ClinVar →

Protein Context — Lollipop Plot

TNFRSF13C · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Immunodeficiency, common variable, 4

MIM #613494

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Tertiary lymphoid structures predict the prognosis and immunotherapy response of cholangiocarcinoma.
Shang T et al.·Front Immunol
2023
A previously unrecognized 22q13.2 microdeletion syndrome that encompasses TCF20 and TNFRSF13C.
Upadia J et al.·Am J Med Genet A
2018Review
Single-cell transcriptomic profiling reveals dysregulation of B-cell subset function in patients with chronic hepatitis B.
Li J et al.·Hepatol Int
2025Cohort
Peripheral Blood Biomarkers CXCL12 and TNFRSF13C Associate with Cerebrospinal Fluid Biomarkers and Infiltrating Immune Cells in Alzheimer Disease.
Wu Q et al.·J Mol Neurosci
2021
Common variable immunodeficiency in children.
Glocker E et al.·Curr Opin Pediatr
2007Review
TNFRSF13C/BAFFR P21R and H159Y polymorphisms in multiple sclerosis.
Ntellas P et al.·Mult Scler Relat Disord
2020
The TNFRSF13C H159Y Variant Is Associated with Severe COVID-19: A Retrospective Study of 500 Patients from Southern Italy.
Russo R et al.·Genes (Basel)
2021Cohort
Genes associated with common variable immunodeficiency: one diagnosis to rule them all?
Bogaert DJ et al.·J Med Genet
2016Review
Identification of tumor associated neutrophils-related genes in triple-negative breast cancer for predicting prognosis and therapeutic response through integrated single-cell analysis.
Li K et al.·Front Immunol
2025
The H159Y Variant of the BAFF-R Gene (TNFRSF13C) Is Unrelated to the Risk of Developing Systemic Lupus Erythematosus and Sjögren's Disease in a Mexican Population.
Borunda-Calderón IM et al.·Int J Mol Sci
2026
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
Chronic Inflammatory Demyelinating PolyradiculoneuropathyNMO Spectrum DisorderMyasthenia Gravis

Safety and Efficacy of BAFF-R CART for Refractory Neuroimmune Diseases

RECRUITING
NCT07022197Phase PHASE1, PHASE2Tianjin Medical University General HospitalStarted 2025-04-10
BAFF-R CART
B-Cell Non-Hodgkin LymphomaRecurrent Chronic Lymphocytic LeukemiaRecurrent Diffuse Large B-Cell Lymphoma

B-Cell Activating Factor Receptor (BAFFR)-Based Chimeric Antigen Receptor T-Cells With Fludarabine and Cyclophosphamide Lymphodepletion for the Treatment of Relapsed or Refractory B-cell Hematologic Malignancies

RECRUITING
NCT06191887Phase PHASE1Mayo ClinicStarted 2024-03-18
Autologous BAFFR-targeting CAR T CellsBendamustineBiopsy

External Resources

Links to major genomics databases and tools