Immunodeficiency 131

Summary

Immunodeficiency 131 (MONDO:0976229) 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 131
Mondo ID	MONDO:0976229
OMIM	621097
DOID	DOID:0061125
UMLS	C6012696
MedGen	1876503
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 › IRF4-related immune disorder › immunodeficiency 131

Related subtypes (1): IRF4-related combined immunodeficiency

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
2762498	NM_002460.4(IRF4):c.1075T>C (p.Phe359Leu)	IRF4	Pathogenic	criteria provided, single submitter
2987365	NM_002460.4(IRF4):c.284C>G (p.Thr95Arg)	IRF4	Pathogenic	criteria provided, single submitter
3731311	IRF4, IVS8, 1213-2, A-G	IRF4	Pathogenic	no assertion criteria provided
3731312	NM_002460.4(IRF4):c.292C>T (p.Arg98Trp)	IRF4	Pathogenic	no assertion criteria provided
4277976	NM_002460.4(IRF4):c.202G>A (p.Ala68Thr)	IRF4	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
IRF4	Orphanet:3452	Whipple disease

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
IRF4	HGNC:6119	ENSG00000137265	Q15306	Interferon regulatory factor 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IRF4	Interferon regulatory factor 4	Transcriptional activator.

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)
IRF4	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf

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
endocervix	1
lymph node	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IRF4	180	broad	marker	lymph node, endocervix, vermiform appendix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IRF4	3,450

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IRF4	Q15306	19

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
Nuclear events stimulated by ALK signaling in cancer	1	326.3×	0.015	IRF4
Signaling by ALK in cancer	1	271.9×	0.015	IRF4
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.015	IRF4
MITF-M-dependent gene expression	1	181.3×	0.015	IRF4
Interferon alpha/beta signaling	1	152.3×	0.015	IRF4
Signaling by ALK fusions and activated point mutants	1	150.3×	0.015	IRF4
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	146.4×	0.015	IRF4
Interferon gamma signaling	1	125.5×	0.015	IRF4
Interferon Signaling	1	120.2×	0.015	IRF4
MITF-M-regulated melanocyte development	1	114.2×	0.015	IRF4
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.015	IRF4
Signaling by Interleukins	1	64.2×	0.022	IRF4
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.023	IRF4
Cytokine Signaling in Immune system	1	40.8×	0.030	IRF4
Developmental Biology	1	14.5×	0.077	IRF4
Disease	1	13.1×	0.077	IRF4
Immune System	1	13.0×	0.077	IRF4

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 T-helper cell differentiation	1	4213.0×	0.004	IRF4
T-helper 17 cell lineage commitment	1	1532.0×	0.004	IRF4
positive regulation of interleukin-13 production	1	1123.5×	0.004	IRF4
myeloid dendritic cell differentiation	1	936.2×	0.004	IRF4
negative regulation of toll-like receptor signaling pathway	1	842.6×	0.004	IRF4
defense response to protozoan	1	601.9×	0.004	IRF4
positive regulation of interleukin-4 production	1	561.7×	0.004	IRF4
positive regulation of interleukin-2 production	1	468.1×	0.004	IRF4
positive regulation of interleukin-10 production	1	401.2×	0.004	IRF4
immune system process	1	391.9×	0.004	IRF4
T cell activation	1	259.3×	0.006	IRF4
positive regulation of cold-induced thermogenesis	1	163.6×	0.008	IRF4
chromatin remodeling	1	73.0×	0.017	IRF4
positive regulation of DNA-templated transcription	1	27.9×	0.041	IRF4
positive regulation of transcription by RNA polymerase II	1	14.9×	0.072	IRF4
regulation of transcription by RNA polymerase II	1	11.7×	0.086	IRF4

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
IRF4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
IRF4	3	Binding:3

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	IRF4

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)
IRF4	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.