Immunodeficiency 132b

Summary

Immunodeficiency 132b (MONDO:0976228) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 132b
Mondo ID	MONDO:0976228
OMIM	621096
DOID	DOID:0061097
UMLS	C6012695
MedGen	1876493
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › immunodeficiency 132b

Related subtypes (94): B cell deficiency, T-cell immunodeficiency, complement deficiency, myalgic encephalomeyelitis/chronic fatigue syndrome, hypoproteinemia, hypercatabolic, X-linked lymphoproliferative syndrome, Wiskott-Aldrich syndrome, autosomal dominant form, immunodeficiency due to CD25 deficiency, immunodeficiency 67, primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency, immunodeficiency 35, pyogenic bacterial infections due to MyD88 deficiency, lymphoproliferative syndrome 1, FADD-related immunodeficiency, immunodeficiency 31B, Wiskott-Aldrich syndrome 2, cryptosporidiosis-chronic cholangitis-liver disease syndrome, idiopathic CD4 lymphocytopenia, immunodeficiency 23, DOCK2 deficiency, immunodeficiency 45, TFRC-related combined immunodeficiency, combined immunodeficiency, autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome, immunodeficiency due to selective anti-polysaccharide antibody deficiency, immunodeficiency 57, immunodeficiency 14b, autosomal recessive, immunodeficiency 98 with autoinflammation, X-linked, immunodeficiency 102, immunodeficiency 74, COVID-19-related, X-linked, immunodeficiency 66, immunodeficiency 80 with or without congenital cardiomyopathy, immunodeficiency 81, immunodeficiency 82 with systemic inflammation, immunodeficiency 84, immunodeficiency 85 and autoimmunity, immunodeficiency 86, immunodeficiency 87 and autoimmunity, immunodeficiency 88, immunodeficiency 89 and autoimmunity, immunodeficiency 91 and hyperinflammation, immunodeficiency 92, immunodeficiency 93 and hypertrophic cardiomyopathy, immunodeficiency 95, immunodeficiency 96, immunodeficiency 97 with autoinflammation, immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, immunodeficiency 101 (varicella zoster virus-specific), immunodeficiency 75, immunodeficiency 76, immunodeficiency 106, susceptibility to viral infections, immunodeficiency 78 with autoimmunity and developmental delay, immunodeficiency 77, immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, immunodeficiency 15a, immunodeficiency 60, immunodeficiency 62, immunodeficiency 63 with lymphoproliferation and autoimmunity, immunodeficiency 64, immunodeficiency 65, susceptibility to viral infections, immunodeficiency 69, immunodeficiency 70, immunodeficiency 72 with autoinflammation, GATA2 deficiency with susceptibility to MDS/AML, Shwachman-Diamond syndrome 1, immunodeficiency 53, immunodeficiency 11b with atopic dermatitis, IKBKG-related immunodeficiency with or without ectodermal dysplasia, FNIP1-associated syndrome, FASLG-related immunodeficiency, TNFRSF9-related immunodeficiency, DNAJC21-related Shwachman Diamond syndrome, IRF4-related immune disorder, PTEN harmartoma tumor syndrome with immune disorder, primary immunodeficiency due to calcium channel deficiency, chronic mucocutaneous candidiasis and connective tissue disease due to JNK1 haploinsufficiency, immune deficiency due to impaired neutrophil phagocytosis and migration, hatipoglu immunodeficiency syndrome, immunodeficiency 112, immunodeficiency 113 with autoimmunity and autoinflammation, immunodeficiency 114, folate-responsive, immunodeficiency 115 with autoinflammation, immunodeficiency 117, immunodeficiency 118, immunodeficiency 119, immunodeficiency 121 with autoinflammation, immunodeficiency 122, immunodeficiency 123 with HPV-related verrucosis, immunodeficiency 125, immunodeficiency 126, susceptibility to, immunodeficiency 127, immunodeficiency 128, immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy, immunodeficiency 134 (Epstein-Barr virus-specific)

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

5 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3731306	NM_145725.3(TRAF3):c.1275C>G (p.Tyr425Ter)	TRAF3	Pathogenic	no assertion criteria provided
3731307	TRAF3, 1-BP DEL, 1066G	TRAF3	Pathogenic	no assertion criteria provided
3731308	NM_145725.3(TRAF3):c.339_340insTAGA (p.Gln114Ter)	TRAF3	Pathogenic	no assertion criteria provided
3731309	Q407*	TRAF3	Pathogenic	no assertion criteria provided
570644	NM_145725.3(TRAF3):c.487C>T (p.Arg163Ter)	TRAF3	Uncertain significance	criteria provided, single submitter

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
TRAF3	Orphanet:1930	Herpes simplex virus encephalitis

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
TRAF3	HGNC:12033	ENSG00000131323	Q13114	TNF receptor-associated factor 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRAF3	TNF receptor-associated factor 3	Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in…

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRAF3	Transcription factor	no		Znf_TRAF, Znf_RING, MATH/TRAF_dom

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
cartilage tissue	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRAF3	258	ubiquitous	marker	cartilage tissue, monocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRAF3	3,493

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRAF3	Q13114	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
TRAF3 deficiency - HSE	1	3806.7×	0.003	TRAF3
Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation	1	951.7×	0.003	TRAF3
TICAM1-dependent activation of IRF3/IRF7	1	815.7×	0.003	TRAF3
TRAF3-dependent IRF activation pathway	1	761.3×	0.003	TRAF3
Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7	1	761.3×	0.003	TRAF3
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway	1	671.8×	0.003	TRAF3
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1	601.0×	0.003	TRAF3
Negative regulators of DDX58/IFIH1 signaling	1	326.3×	0.004	TRAF3
Ovarian tumor domain proteases	1	278.5×	0.004	TRAF3
SARS-CoV-1 activates/modulates innate immune responses	1	271.9×	0.004	TRAF3
TNFR2 non-canonical NF-kB pathway	1	181.3×	0.006	TRAF3
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.011	TRAF3

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
regulation of interferon-beta production	1	3370.4×	0.003	TRAF3
Toll signaling pathway	1	2407.4×	0.003	TRAF3
regulation of defense response to virus	1	2106.5×	0.003	TRAF3
TRIF-dependent toll-like receptor signaling pathway	1	1532.0×	0.003	TRAF3
regulation of proteolysis	1	1296.3×	0.003	TRAF3
toll-like receptor signaling pathway	1	601.9×	0.005	TRAF3
toll-like receptor 4 signaling pathway	1	526.6×	0.005	TRAF3
regulation of canonical NF-kappaB signal transduction	1	481.5×	0.005	TRAF3
positive regulation of type I interferon production	1	421.3×	0.005	TRAF3
obsolete negative regulation of NF-kappaB transcription factor activity	1	358.6×	0.005	TRAF3
type I interferon-mediated signaling pathway	1	343.9×	0.005	TRAF3
tumor necrosis factor-mediated signaling pathway	1	330.4×	0.005	TRAF3
regulation of cytokine production	1	247.8×	0.006	TRAF3
regulation of apoptotic process	1	83.4×	0.015	TRAF3
defense response to virus	1	69.3×	0.017	TRAF3
cell surface receptor signaling pathway	1	64.1×	0.018	TRAF3
apoptotic process	1	28.7×	0.037	TRAF3
signal transduction	1	16.1×	0.062	TRAF3

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
TRAF3	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	TRAF3

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)
TRAF3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.