Inflammatory bowel disease 30

Summary

Inflammatory bowel disease 30 (MONDO:0033643) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inflammatory bowel disease 30
Mondo ID	MONDO:0033643
OMIM	619079
DOID	DOID:0112154
UMLS	C5436750
MedGen	1737985
Is cancer (heuristic)	no

Also known as: IBD30 · inflammatory bowel disease (Crohn disease) 30

Data availability: 10 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inflammatory bowel disease › inflammatory bowel disease 30

Related subtypes (39): Crohn disease, colitis, proctitis, ulcerative proctosigmoiditis, inflammatory bowel disease 11, cutaneous photosensitivity-lethal colitis syndrome, inflammatory bowel disease 1, inflammatory bowel disease 2, inflammatory bowel disease 3, inflammatory bowel disease 7, inflammatory bowel disease 5, inflammatory bowel disease 8, inflammatory bowel disease 6, inflammatory bowel disease 4, inflammatory bowel disease 9, inflammatory bowel disease 10, inflammatory bowel disease 12, inflammatory bowel disease 13, inflammatory bowel disease 14, inflammatory bowel disease 15, inflammatory bowel disease 16, inflammatory bowel disease 17, inflammatory bowel disease 18, inflammatory bowel disease 19, inflammatory bowel disease 20, inflammatory bowel disease 21, inflammatory bowel disease 22, inflammatory bowel disease 23, inflammatory bowel disease 24, inflammatory bowel disease 26, inflammatory bowel disease 27, undetermined colitis, cap polyposis, IL10-related early-onset inflammatory bowel disease, neonatal inflammatory skin and bowel disease, inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessive, TRIM22-related inflammatory bowel disease, ALPI-related inflammatory bowel disease, inflammatory bowel disease 29

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

10 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 1 likely benign, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4687999	NM_001184900.3(CARD8):c.180dup (p.Gln61fs)	CARD8	Likely pathogenic	criteria provided, single submitter
3778999	NM_001184900.3(CARD8):c.330A>C (p.Leu110=)	CARD8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1036812	NM_001184900.3(CARD8):c.970C>T (p.His324Tyr)	CARD8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1416149	NM_001184900.3(CARD8):c.542G>A (p.Ser181Asn)	CARD8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1516002	NM_001184900.3(CARD8):c.853G>T (p.Glu285Ter)	CARD8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1709259	NM_001184900.3(CARD8):c.139A>G (p.Ser47Gly)	CARD8	Uncertain significance	criteria provided, single submitter
252559	NM_001184900.3(CARD8):c.130G>A (p.Val44Ile)	CARD8	Uncertain significance	criteria provided, single submitter
3393338	NM_001184900.3(CARD8):c.1207T>G (p.Ser403Ala)	CARD8	Uncertain significance	criteria provided, single submitter
3902042	NM_001184900.3(CARD8):c.275A>G (p.Asp92Gly)	CARD8	Uncertain significance	criteria provided, single submitter
3064763	NM_001184900.3(CARD8):c.1015A>G (p.Ser339Gly)	CARD8	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
CARD8	Limited	Unknown	inflammatory bowel disease 30

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CARD8	Orphanet:714410	CARD8-related inflammatory bowel 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
CARD8	HGNC:17057	ENSG00000105483	Q9Y2G2	Caspase recruitment domain-containing protein 8	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CARD8	Caspase recruitment domain-containing protein 8	Inflammasome sensor, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis of CD4(+) T-cells and macrophages.

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)
CARD8	Other/Unknown	no		CARD, DEATH-like_dom_sf, FIIND_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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CARD8	260	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CARD8	905

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CARD8	Q9Y2G2	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Formation of apoptosome	1	1427.5×	0.002	CARD8
Cytochrome c-mediated apoptotic response	1	1268.9×	0.002	CARD8
Regulation of the apoptosome activity	1	1038.2×	0.002	CARD8
Apoptotic factor-mediated response	1	878.5×	0.002	CARD8
Intrinsic Pathway for Apoptosis	1	292.8×	0.005	CARD8
Apoptosis	1	167.9×	0.007	CARD8
Programmed Cell Death	1	146.4×	0.007	CARD8

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
CARD8 inflammasome complex assembly	1	16852.0×	9e-04	CARD8
self proteolysis	1	1532.0×	0.004	CARD8
negative regulation of lipopolysaccharide-mediated signaling pathway	1	1123.5×	0.004	CARD8
negative regulation of NLRP3 inflammasome complex assembly	1	991.3×	0.004	CARD8
negative regulation of interleukin-1 beta production	1	510.7×	0.005	CARD8
activation of innate immune response	1	481.5×	0.005	CARD8
negative regulation of tumor necrosis factor-mediated signaling pathway	1	455.5×	0.005	CARD8
intrinsic apoptotic signaling pathway	1	358.6×	0.006	CARD8
protein destabilization	1	290.6×	0.006	CARD8
positive regulation of interleukin-1 beta production	1	259.3×	0.006	CARD8
antiviral innate immune response	1	227.7×	0.006	CARD8
negative regulation of canonical NF-kappaB signal transduction	1	172.0×	0.008	CARD8
positive regulation of inflammatory response	1	145.3×	0.008	CARD8
regulation of apoptotic process	1	83.4×	0.014	CARD8
defense response to virus	1	69.3×	0.015	CARD8
inflammatory response	1	37.7×	0.027	CARD8

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
CARD8	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	CARD8

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)
CARD8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.