Immunodeficiency, common variable, 3

Summary

Immunodeficiency, common variable, 3 (MONDO:0013283) is a disease caused by CD19 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CD19 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 61

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency, common variable, 3
Mondo ID	MONDO:0013283
OMIM	613493
DOID	DOID:0081146
UMLS	C3150738
MedGen	462088
GARD	0015668
Is cancer (heuristic)	no

Also known as: CVID3 · immunodeficiency, common variable, 3 · immunodeficiency, common variable, type 3

Data availability: 61 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic agammaglobulinemia › common variable immunodeficiency › immunodeficiency, common variable, 3

Related subtypes (15): immune deficiency, familial variable, immunodeficiency, common variable, 2, immunodeficiency, common variable, 1, immunodeficiency, common variable, 4, immunodeficiency, common variable, 5, immunodeficiency, common variable, 6, immunodeficiency, common variable, 7, combined immunodeficiency due to LRBA deficiency, immunodeficiency, common variable, 10, IL21-related infantile inflammatory bowel disease, immunodeficiency, common variable, 12, pancytopenia due to IKZF1 mutations, immunodeficiency, common variable, 14, immunodeficiency, common variable, due to APRIL deficiency, immunodeficiency, common variable, 15

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

61 retrieved; paginated sample, class counts are floors:

34 uncertain significance, 12 conflicting classifications of pathogenicity, 6 pathogenic, 4 benign/likely benign, 3 benign, 1 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
18054	NM_001770.6(CD19):c.971dup (p.Arg325fs)	CD19	Pathogenic	no assertion criteria provided
18055	NM_001770.6(CD19):c.1386_1387del (p.Asn463fs)	CD19	Pathogenic	no assertion criteria provided
254194	NM_001770.6(CD19):c.947-1G>T	CD19	Pathogenic	no assertion criteria provided
254195	NM_001770.6(CD19):c.156G>C (p.Trp52Cys)	CD19	Pathogenic	no assertion criteria provided
254196	NM_001770.6(CD19):c.1464del (p.Ser489fs)	CD19	Pathogenic	no assertion criteria provided
254197	NM_001770.5(CD19):c.1653_*9delins23	CD19	Pathogenic	no assertion criteria provided
811565	NM_001770.6(CD19):c.1198+2T>G	CD19	Likely pathogenic	criteria provided, single submitter
1638553	NM_001770.6(CD19):c.1487-11C>G	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318797	NM_001770.6(CD19):c.171G>A (p.Pro57=)	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318799	NM_001770.6(CD19):c.384C>T (p.Asp128=)	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318800	NM_001770.6(CD19):c.390T>A (p.Gly130=)	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318801	NM_001770.6(CD19):c.395T>G (p.Leu132Arg)	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318806	NM_001770.6(CD19):c.836-13C>G	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318808	NM_001770.6(CD19):c.1274C>T (p.Ser425Phe)	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318810	NM_001770.6(CD19):c.1371C>T (p.Asn457=)	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318812	NM_001770.6(CD19):c.1580-14C>T	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318813	NM_001770.6(CD19):c.1580-4C>A	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
723603	NM_001770.6(CD19):c.147G>A (p.Gln49=)	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
886037	NM_001770.6(CD19):c.323A>C (p.Gln108Pro)	CD19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1013096	NM_001770.6(CD19):c.170C>T (p.Pro57Leu)	CD19	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033867	NM_001770.6(CD19):c.228G>T (p.Arg76Ser)	CD19	Uncertain significance	criteria provided, multiple submitters, no conflicts
1430236	NM_001770.6(CD19):c.1035G>C (p.Gln345His)	CD19	Uncertain significance	criteria provided, multiple submitters, no conflicts
1963428	NM_001770.6(CD19):c.704C>T (p.Pro235Leu)	CD19	Uncertain significance	criteria provided, multiple submitters, no conflicts
235527	NM_001770.6(CD19):c.835+3A>G	CD19	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439814	NM_001770.6(CD19):c.24C>A (p.Phe8Leu)	CD19	Uncertain significance	criteria provided, single submitter
318795	NM_001770.6(CD19):c.-16G>A	CD19	Uncertain significance	criteria provided, single submitter
318796	NM_001770.6(CD19):c.17T>G (p.Leu6Arg)	CD19	Uncertain significance	criteria provided, single submitter
318804	NM_001770.6(CD19):c.527C>T (p.Pro176Leu)	CD19	Uncertain significance	criteria provided, multiple submitters, no conflicts
318807	NM_001770.6(CD19):c.1204G>A (p.Glu402Lys)	CD19	Uncertain significance	criteria provided, multiple submitters, no conflicts
318814	NM_001770.6(CD19):c.*11G>A	CD19	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CD19	Definitive	Autosomal recessive	immunodeficiency, common variable, 3	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CD19	Orphanet:696881	Common variable immunodeficiency phenotype due to CD19/CD81 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
CD19	HGNC:1633	ENSG00000177455	P15391	B-lymphocyte antigen CD19	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD19	B-lymphocyte antigen CD19	Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CD19	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig-like_fold

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
lymph node	1
spleen	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD19	164	tissue_specific	marker	spleen, lymph node, vermiform appendix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD19	3,552

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CD19	P15391	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. 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
Complement cascade	1	634.4×	0.012	CD19
PI3K/AKT Signaling in Cancer	1	368.4×	0.012	CD19
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	356.9×	0.012	CD19
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.012	CD19
Negative regulation of the PI3K/AKT network	1	278.5×	0.012	CD19
Regulation of Complement cascade	1	233.1×	0.012	CD19
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.019	CD19
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.020	CD19
Intracellular signaling by second messengers	1	91.4×	0.020	CD19
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.020	CD19
PIP3 activates AKT signaling	1	66.8×	0.023	CD19
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.025	CD19
Adaptive Immune System	1	29.8×	0.044	CD19
Innate Immune System	1	25.5×	0.048	CD19
Disease	1	13.1×	0.082	CD19
Immune System	1	13.0×	0.082	CD19
Signal Transduction	1	10.2×	0.098	CD19

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
B-1 B cell differentiation	1	8426.0×	7e-04	CD19
regulation of B cell activation	1	5617.3×	7e-04	CD19
B cell proliferation involved in immune response	1	2808.7×	7e-04	CD19
antigen receptor-mediated signaling pathway	1	2808.7×	7e-04	CD19
regulation of B cell receptor signaling pathway	1	2808.7×	7e-04	CD19
immunoglobulin mediated immune response	1	702.2×	0.002	CD19
positive regulation of release of sequestered calcium ion into cytosol	1	495.6×	0.003	CD19
B cell proliferation	1	481.5×	0.003	CD19
B cell receptor signaling pathway	1	401.2×	0.003	CD19
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.013	CD19

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CD19	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	1	CD19
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
CD19	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.