TNFRSF13B

TNF receptor superfamily member 13B, the group of CD molecules|Tumor necrosis factor receptor superfamily

Basic information

Region (hg38): 17:16929816-16972118

Links

ENSG00000240505

∙ NCBI:23495 ∙ OMIM:604907 ∙ HGNC:18153 ∙ Uniprot:O14836 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

immunodeficiency, common variable, 2 (Strong), mode of inheritance: AR
immunodeficiency, common variable, 2 (Strong), mode of inheritance: AR
common variable immunodeficiency (Supportive), mode of inheritance: AD
immunodeficiency, common variable, 2 (Strong), mode of inheritance: AR
immunodeficiency, common variable, 2 (Limited), mode of inheritance: AD
immunodeficiency, common variable, 2 (Definitive), mode of inheritance: AR
immunodeficiency, common variable, 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunoglobulin A deficiency 2; Common variable immunodeficiency 2	AD/AR	Allergy/Immunology/Infectious	In CVID2, prophylaxis and early and aggressive treatment of infections may be beneficial; In most cases, IGA deficiency 2 is not associated with any illness, though some may have increased infections and autoimmune disorders (other sequelae have been reported, but the molecular causes in these patients are unclear)	Allergy/Immunology/Infectious	11720003; 16007086; 16049503; 16007087; 18981294; 19629655; 20156508; 22076597; 22627058

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNFRSF13B gene.

Immunodeficiency,_common_variable,_2 (309 variants)
not_provided (66 variants)
Inborn_genetic_diseases (34 variants)
not_specified (23 variants)
TNFRSF13B-related_disorder (22 variants)
Immunoglobulin_A_deficiency_2 (19 variants)
Common_Variable_Immune_Deficiency,_Dominant (12 variants)
Common_variable_immunodeficiency (4 variants)
Immunodeficiency,_common_variable,_1 (4 variants)
Immune_deficiency,_familial_variable (1 variants)
IgAD1 (1 variants)
Immunodeficiency,_common_variable,_10 (1 variants)
See_cases (1 variants)
Severe_SARS-CoV-2_infection,_susceptibility_to (1 variants)
Hyper-IgM_syndrome_type_2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNFRSF13B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000012452.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	67 clinvar	3 clinvar	74
missense	2 clinvar	5 clinvar	160 clinvar	15 clinvar		182
nonsense	8 clinvar	4 clinvar	3 clinvar			15
start loss			1			1
frameshift	10 clinvar	4 clinvar	9 clinvar			23
splice donor/acceptor (+/-2bp)	5 clinvar	2 clinvar	1 clinvar			8
Total	25	15	178	82	3

Highest pathogenic variant AF is 0.005440998

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNFRSF13B	protein_coding	protein_coding	ENST00000261652	5	42584

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.09e-15	0.000589	125547	0	201	125748	0.000800

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.20	215	171	1.26	0.0000103	1895
Missense in Polyphen		69	41.182	1.6755		566
Synonymous	-0.988	82	71.4	1.15	0.00000443	589
Loss of Function	-2.17	18	10.4	1.73	5.35e-7	123

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000879	0.000879
Ashkenazi Jewish	0.00507	0.00507
East Asian	0.00109	0.00109
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000768	0.000756
Middle Eastern	0.00109	0.00109
South Asian	0.000294	0.000294
Other	0.000815	0.000815

dbNSFP

Source: dbNSFP

Function: FUNCTION: Receptor for TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS that binds both ligands with similar high affinity. Mediates calcineurin-dependent activation of NF-AT, as well as activation of NF-kappa-B and AP-1. Involved in the stimulation of B- and T- cell function and the regulation of humoral immunity. {ECO:0000269|PubMed:10956646, ECO:0000269|PubMed:10973284}.;
Disease: DISEASE: Immunoglobulin A deficiency 2 (IGAD2) [MIM:609529]: Selective deficiency of immunoglobulin A (IGAD) is the most common form of primary immunodeficiency, with an incidence of approximately 1 in 600 individuals in the western world. Individuals with symptomatic IGAD often have deficiency of IgG subclasses or decreased antibody response to carbohydrate antigens such as pneumococcal polysaccharide vaccine. Individuals with IGAD also suffer from recurrent sinopulmonary and gastrointestinal infections and have an increased incidence of autoimmune disorders and of lymphoid and non-lymphoid malignancies. In vitro studies have suggested that some individuals with IGAD have impaired isotype class switching to IgA and others may have a post-switch defect. IGAD and CVID have been known to coexist in families. Some individuals initially present with IGAD1 and then develop CVID. These observations suggest that some cases of IGAD and CVID may have a common etiology. {ECO:0000269|PubMed:16007086}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Primary immunodeficiency - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Intestinal immune network for IgA production - Homo sapiens (human);yaci and bcma stimulation of b cell immune responses;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;Immune System;TNFs bind their physiological receptors;Syndecan-4-mediated signaling events;Syndecan-2-mediated signaling events (Consensus)

Recessive Scores

pRec: 0.245

Intolerance Scores

loftool: 0.218
rvis_EVS: 0.53
rvis_percentile_EVS: 80.96

Haploinsufficiency Scores

pHI: 0.0639
hipred: N
hipred_score: 0.180
ghis: 0.569

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.953

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Tnfrsf13b
Phenotype: homeostasis/metabolism phenotype; renal/urinary system phenotype; immune system phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; liver/biliary system phenotype;

Gene ontology

Biological process: B cell homeostasis;hematopoietic progenitor cell differentiation;adaptive immune response;cell surface receptor signaling pathway;negative regulation of B cell proliferation;tumor necrosis factor-mediated signaling pathway
Cellular component: plasma membrane;integral component of plasma membrane
Molecular function: protein binding;signaling receptor activity