immunoglobulin A deficiency 2

Summary

immunoglobulin A deficiency 2 (MONDO:0012291) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunoglobulin A deficiency 2
Mondo ID	MONDO:0012291
MeSH	C536291
OMIM	609529
UMLS	C1836032
MedGen	372182
GARD	0010198
Is cancer (heuristic)	no

Also known as: IgA, selective deficiency of, TACI related · IGAD2 · immunoglobulin a deficiency 2 · Immunoglobulin a deficiency type 2 · Immunoglobulin A, selective deficiency of, TACI related · selective IgA deficiency disease caused by mutation in TNFRSF13B · TNFRSF13B selective IgA deficiency disease

Data availability: 20 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › B cell deficiency › selective immunoglobulin deficiency disease › dysgammaglobulinemia › selective IgA deficiency disease › immunoglobulin A deficiency 2

Related subtypes (2): IgAD1, secretory component deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

20 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 7 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 1 likely benign, 1 conflicting classifications of pathogenicity; risk factor, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1455440	NM_012452.3(TNFRSF13B):c.61+1G>A	TNFRSF13B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
203368	NM_012452.3(TNFRSF13B):c.492C>G (p.Tyr164Ter)	TNFRSF13B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
322029	NM_012452.3(TNFRSF13B):c.204dup (p.Leu69fs)	TNFRSF13B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
840923	NM_012452.3(TNFRSF13B):c.198C>A (p.Cys66Ter)	TNFRSF13B	Pathogenic	criteria provided, multiple submitters, no conflicts
1034403	NM_012452.3(TNFRSF13B):c.361C>T (p.Gln121Ter)	TNFRSF13B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
281110	NM_012452.3(TNFRSF13B):c.236A>G (p.Tyr79Cys)	TNFRSF13B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
322026	NM_012452.3(TNFRSF13B):c.592C>T (p.Arg198Cys)	TNFRSF13B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5302	NM_012452.3(TNFRSF13B):c.310T>C (p.Cys104Arg)	TNFRSF13B	Conflicting classifications of pathogenicity; risk factor	criteria provided, conflicting classifications
5303	NM_012452.3(TNFRSF13B):c.542C>A (p.Ala181Glu)	TNFRSF13B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
538714	NM_012452.3(TNFRSF13B):c.641T>C (p.Met214Thr)	TNFRSF13B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
618436	NM_012452.3(TNFRSF13B):c.260T>A (p.Ile87Asn)	TNFRSF13B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626190	NM_012452.3(TNFRSF13B):c.145T>C (p.Ser49Pro)	TNFRSF13B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031204	NM_012452.3(TNFRSF13B):c.693C>G (p.Ser231Arg)	TNFRSF13B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1376163	NM_012452.3(TNFRSF13B):c.34C>T (p.Arg12Trp)	TNFRSF13B	Uncertain significance	criteria provided, multiple submitters, no conflicts
538709	NM_012452.3(TNFRSF13B):c.706G>T (p.Glu236Ter)	TNFRSF13B	Uncertain significance	criteria provided, multiple submitters, no conflicts
577672	NM_012452.3(TNFRSF13B):c.58C>T (p.Arg20Cys)	TNFRSF13B	Uncertain significance	criteria provided, multiple submitters, no conflicts
636449	NM_012452.3(TNFRSF13B):c.53A>G (p.Glu18Gly)	TNFRSF13B	Uncertain significance	criteria provided, multiple submitters, no conflicts
803326	NM_012452.3(TNFRSF13B):c.118T>C (p.Trp40Arg)	TNFRSF13B	Uncertain significance	criteria provided, multiple submitters, no conflicts
840913	NM_012452.3(TNFRSF13B):c.214C>T (p.Arg72Cys)	TNFRSF13B	Uncertain significance	criteria provided, multiple submitters, no conflicts
322027	NM_012452.3(TNFRSF13B):c.215G>A (p.Arg72His)	TNFRSF13B	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNFRSF13B	Orphanet:696907	Common variable immunodeficiency phenotype due to homozygous TACI deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TNFRSF13B	HGNC:18153	ENSG00000240505	O14836	Tumor necrosis factor receptor superfamily member 13B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNFRSF13B	Tumor necrosis factor receptor superfamily member 13B	Receptor for TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS that binds both ligands with similar high affinity.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNFRSF13B	Other/Unknown	no		TACI_Cys-rich-dom, TNFR_13B

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
olfactory bulb	1
spleen	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNFRSF13B	158	tissue_specific	marker	type B pancreatic cell, olfactory bulb, spleen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNFRSF13B	1,333

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNFRSF13B	O14836	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TNFs bind their physiological receptors	1	393.8×	0.003	TNFRSF13B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of B cell proliferation	1	936.2×	0.004	TNFRSF13B
B cell homeostasis	1	561.7×	0.004	TNFRSF13B
hematopoietic progenitor cell differentiation	1	237.3×	0.007	TNFRSF13B
adaptive immune response	1	84.3×	0.015	TNFRSF13B
cell surface receptor signaling pathway	1	64.1×	0.016	TNFRSF13B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TNFRSF13B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TNFRSF13B

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TNFRSF13B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.