Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome

Summary

Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome (MONDO:0033968) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome
Mondo ID	MONDO:0033968
Orphanet	529977
UMLS	C5568533
MedGen	1799956
GARD	0022204
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome

Related subtypes (40): B cell deficiency, complement deficiency, phagocyte bactericidal dysfunction, trichohepatoenteric syndrome, hepatic veno-occlusive disease-immunodeficiency syndrome, immunodeficiency with defective T-cell response to interleukin 1, Say-Barber-Miller syndrome, familial isolated congenital asplenia, X-linked immunoneurologic disorder, ectodermal dysplasia and immune deficiency, immunodeficiency 33, immunodeficiency 47, combined immunodeficiency due to moesin deficiency, immunodeficiency, X-linked, with deficiency of 115,000 Dalton surface glycoprotein, properdin deficiency, X-linked, combined immunodeficiency with faciooculoskeletal anomalies, recurrent infections associated with rare immunoglobulin isotypes deficiency, immunodeficiency 28, autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity, immunodeficiency 37, immunodeficiency 39, BENTA disease, primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection, immunodeficiency 49, chronic mucocutaneous candidiasis, hereditary hemophagocytic lymphohistiocytosis, immunoglobulin heavy chain deficiency, immuno-osseous dysplasia, lymphoproliferative syndrome, IL10-related early-onset inflammatory bowel disease, T-cell immunodeficiency with epidermodysplasia verruciformis, Aicardi-Goutieres syndrome, inflammatory bowel disease-recurrent sinopulmonary infections syndrome, A20 haploinsufficiency, NK cell deficiency, T cell and NK cell immunodeficiency, dendritic cell deficiency, immunodysregulation with variable immunodeficiency and autoimmunity, immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency, STAT5 haploinsufficiency

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
RIPK1	Supportive	Autosomal recessive	immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RIPK1	Orphanet:529977	Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome

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
RIPK1	HGNC:10019	ENSG00000137275	Q13546	Receptor-interacting serine/threonine-protein kinase 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RIPK1	Receptor-interacting serine/threonine-protein kinase 1	Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RIPK1	Kinase	yes	2.7.10.2	Death_dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_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
granulocyte	1
right lobe of liver	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RIPK1	238	ubiquitous	marker	granulocyte, sural nerve, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RIPK1	4,129

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RIPK1	Q13546	39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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
SARS-CoV-1-mediated effects on programmed cell death	1	3806.7×	0.003	RIPK1
Microbial modulation of RIPK1-mediated regulated necrosis	1	2855.0×	0.003	RIPK1
TLR3-mediated TICAM1-dependent programmed cell death	1	1903.3×	0.003	RIPK1
Defective RIPK1-mediated regulated necrosis	1	1903.3×	0.003	RIPK1
TRIF-mediated programmed cell death	1	1268.9×	0.003	RIPK1
Regulation by c-FLIP	1	1038.2×	0.003	RIPK1
CASP8 activity is inhibited	1	1038.2×	0.003	RIPK1
Dimerization of procaspase-8	1	1038.2×	0.003	RIPK1
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10	1	878.5×	0.003	RIPK1
Caspase activation via Death Receptors in the presence of ligand	1	761.3×	0.003	RIPK1
Dengue virus modulates apoptosis	1	713.8×	0.003	RIPK1
RIP-mediated NFkB activation via ZBP1	1	671.8×	0.003	RIPK1
TICAM1, RIP1-mediated IKK complex recruitment	1	601.0×	0.003	RIPK1
IKK complex recruitment mediated by RIP1	1	496.5×	0.003	RIPK1
RIPK1-mediated regulated necrosis	1	456.8×	0.003	RIPK1
TNFR1-induced proapoptotic signaling	1	439.2×	0.003	RIPK1
Regulation of necroptotic cell death	1	439.2×	0.003	RIPK1
TNF signaling	1	423.0×	0.003	RIPK1
TRP channels	1	407.9×	0.003	RIPK1
TNFR1-induced NF-kappa-B signaling pathway	1	335.9×	0.004	RIPK1
Ovarian tumor domain proteases	1	278.5×	0.004	RIPK1
Regulation of TNFR1 signaling	1	223.9×	0.005	RIPK1
Potential therapeutics for SARS	1	114.2×	0.009	RIPK1
Ub-specific processing proteases	1	53.1×	0.019	RIPK1

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
ripoptosome assembly	1	16852.0×	0.001	RIPK1
positive regulation of miRNA processing	1	16852.0×	0.001	RIPK1
positive regulation of interleukin-6-mediated signaling pathway	1	5617.3×	0.002	RIPK1
ripoptosome assembly involved in necroptotic process	1	5617.3×	0.002	RIPK1
positive regulation of programmed necrotic cell death	1	4213.0×	0.002	RIPK1
peptidyl-serine autophosphorylation	1	3370.4×	0.002	RIPK1
positive regulation of necroptotic process	1	2808.7×	0.002	RIPK1
programmed necrotic cell death	1	2106.5×	0.003	RIPK1
necroptotic signaling pathway	1	2106.5×	0.003	RIPK1
T cell apoptotic process	1	1296.3×	0.003	RIPK1
positive regulation of macrophage differentiation	1	1203.7×	0.003	RIPK1
positive regulation of programmed cell death	1	1123.5×	0.003	RIPK1
necroptotic process	1	1053.2×	0.003	RIPK1
positive regulation of tumor necrosis factor-mediated signaling pathway	1	1053.2×	0.003	RIPK1
negative regulation of necroptotic process	1	991.3×	0.003	RIPK1
positive regulation of execution phase of apoptosis	1	842.6×	0.004	RIPK1
response to tumor necrosis factor	1	624.1×	0.004	RIPK1
amyloid fibril formation	1	601.9×	0.004	RIPK1
positive regulation of reactive oxygen species metabolic process	1	510.7×	0.005	RIPK1
positive regulation of extrinsic apoptotic signaling pathway	1	455.5×	0.005	RIPK1
negative regulation of extrinsic apoptotic signaling pathway	1	421.3×	0.005	RIPK1
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	411.0×	0.005	RIPK1
canonical NF-kappaB signal transduction	1	366.4×	0.006	RIPK1
tumor necrosis factor-mediated signaling pathway	1	330.4×	0.006	RIPK1
cellular response to growth factor stimulus	1	318.0×	0.006	RIPK1
extrinsic apoptotic signaling pathway	1	306.4×	0.006	RIPK1
positive regulation of protein phosphorylation	1	276.3×	0.006	RIPK1
positive regulation of neuron apoptotic process	1	271.8×	0.006	RIPK1
positive regulation of non-canonical NF-kappaB signal transduction	1	255.3×	0.006	RIPK1
positive regulation of interleukin-8 production	1	244.2×	0.006	RIPK1

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RIPK1	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RIPK1	24	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	RIPK1
FEDRATINIB	4	RIPK1
AXITINIB	4	RIPK1
SORAFENIB	4	RIPK1
DABRAFENIB	4	RIPK1
PAZOPANIB	4	RIPK1
NINTEDANIB	4	RIPK1
SUNITINIB	4	RIPK1
QUIZARTINIB	4	RIPK1
CRIZOTINIB	4	RIPK1
LINIFANIB	3	RIPK1
DOVITINIB	3	RIPK1
FORETINIB	2	RIPK1
SU-014813	2	RIPK1
REBASTINIB	2	RIPK1
FEXAGRATINIB	2	RIPK1
GSK2982772	2	RIPK1
ECLITASERTIB	2	RIPK1
FLIZASERTIB	2	RIPK1
OCADUSERTIB	2	RIPK1
RAF-265	2	RIPK1
TOZASERTIB	2	RIPK1
KW-2449	1	RIPK1
AST-487	1	RIPK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
RIPK1	400	Binding:391, ADMET:7, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RIPK1	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
RIPK1	400

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

24 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.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	RIPK1
FEDRATINIB	4	RIPK1
AXITINIB	4	RIPK1
SORAFENIB	4	RIPK1
DABRAFENIB	4	RIPK1
PAZOPANIB	4	RIPK1
NINTEDANIB	4	RIPK1
SUNITINIB	4	RIPK1
QUIZARTINIB	4	RIPK1
CRIZOTINIB	4	RIPK1
LINIFANIB	3	RIPK1
DOVITINIB	3	RIPK1
FORETINIB	2	RIPK1
SU-014813	2	RIPK1
REBASTINIB	2	RIPK1
FEXAGRATINIB	2	RIPK1
GSK2982772	2	RIPK1
ECLITASERTIB	2	RIPK1
FLIZASERTIB	2	RIPK1
OCADUSERTIB	2	RIPK1
RAF-265	2	RIPK1
TOZASERTIB	2	RIPK1
KW-2449	1	RIPK1
AST-487	1	RIPK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RIPK1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.