IL21-related infantile inflammatory bowel disease

Summary

IL21-related infantile inflammatory bowel disease (MONDO:0014338) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	IL21-related infantile inflammatory bowel disease
Mondo ID	MONDO:0014338
OMIM	615767
Orphanet	477661
DOID	DOID:0081153
NCIT	C176801
UMLS	C5567788
MedGen	1799211
GARD	0017852
Is cancer (heuristic)	no

Also known as: CVID11 · IL21-related infantile IBD · immunodeficiency, common variable, 11 · immunodeficiency, common variable, type 11

Data availability: 3 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic agammaglobulinemia › common variable immunodeficiency › IL21-related infantile inflammatory bowel disease

Related subtypes (15): immune deficiency, familial variable, immunodeficiency, common variable, 2, immunodeficiency, common variable, 1, immunodeficiency, common variable, 3, 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, 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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 benign, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
127140	NM_021803.4(IL21):c.146T>C (p.Leu49Pro)	IL21	Pathogenic	no assertion criteria provided
945417	NM_021803.4(IL21):c.119G>A (p.Arg40His)	IL21	Uncertain significance	criteria provided, multiple submitters, no conflicts
402975	NM_021803.4(IL21):c.234C>T (p.Cys78=)	IL21	Benign	criteria provided, multiple submitters, no conflicts

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
IL21	Supportive	Autosomal recessive	IL21-related infantile inflammatory bowel disease	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL21	Orphanet:477661	IL21-related infantile 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
IL21	HGNC:6005	ENSG00000138684	Q9HBE4	Interleukin-21	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL21	Interleukin-21	Cytokine with immunoregulatory activity.

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)
IL21	Other/Unknown	no		IL-15/IL-21_fam, 4_helix_cytokine-like_core

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
male germ line stem cell (sensu Vertebrata) in testis	1
olfactory bulb	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL21	26		marker	male germ line stem cell (sensu Vertebrata) in testis, olfactory bulb, type B pancreatic cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL21	1,080

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL21	Q9HBE4	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Interleukin-21 signaling	1	1142.0×	9e-04	IL21

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
tyrosine phosphorylation of STAT protein	1	2808.7×	0.003	IL21
positive regulation of tissue remodeling	1	2808.7×	0.003	IL21
positive regulation of natural killer cell cytokine production	1	1872.4×	0.003	IL21
germinal center B cell differentiation	1	1685.2×	0.003	IL21
positive regulation of natural killer cell differentiation	1	1685.2×	0.003	IL21
T follicular helper cell differentiation	1	1404.3×	0.003	IL21
natural killer cell differentiation	1	887.0×	0.004	IL21
positive regulation of tyrosine phosphorylation of STAT protein	1	732.7×	0.004	IL21
positive regulation of interleukin-17 production	1	601.9×	0.004	IL21
positive regulation of natural killer cell mediated cytotoxicity	1	561.7×	0.004	IL21
positive regulation of immunoglobulin production	1	481.5×	0.004	IL21
cell maturation	1	443.5×	0.004	IL21
natural killer cell mediated cytotoxicity	1	432.1×	0.004	IL21
positive regulation of interleukin-10 production	1	401.2×	0.004	IL21
positive regulation of B cell proliferation	1	343.9×	0.004	IL21
positive regulation of cytokine production	1	271.8×	0.005	IL21
positive regulation of T cell proliferation	1	259.3×	0.005	IL21
positive regulation of type II interferon production	1	224.7×	0.006	IL21
cellular response to virus	1	200.6×	0.006	IL21
positive regulation of inflammatory response	1	145.3×	0.008	IL21
defense response to virus	1	69.3×	0.016	IL21
positive regulation of cell population proliferation	1	33.6×	0.031	IL21
signal transduction	1	16.1×	0.062	IL21

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
IL21	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	IL21

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)
IL21	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.