Type 1 diabetes mellitus 10

Summary

Type 1 diabetes mellitus 10 (MONDO:0011168) is a disease caused by IL2RA (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: IL2RA (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	type 1 diabetes mellitus 10
Mondo ID	MONDO:0011168
MeSH	C566602
OMIM	601942
DOID	DOID:0110749
UMLS	C1866040
MedGen	400903
Is cancer (heuristic)	no

Also known as: diabetes mellitus, insulin-dependent, 10 · diabetes mellitus, insulin-dependent, type 10 · IDDM10 · IL2RA type 1 diabetes mellitus · insulin-dependent diabetes mellitus 10 · type 1 diabetes mellitus caused by mutation in IL2RA

Data availability: 7 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › diabetes mellitus, insulin-dependent, X-linked, susceptibility to › type 1 diabetes mellitus 10

Related subtypes (20): type 1 diabetes mellitus 2, type 1 diabetes mellitus 1, type 1 diabetes mellitus 3, type 1 diabetes mellitus 4, type 1 diabetes mellitus 5, type 1 diabetes mellitus 7, type 1 diabetes mellitus 8, type 1 diabetes mellitus 11, type 1 diabetes mellitus 13, type 1 diabetes mellitus 12, type 1 diabetes mellitus 15, type 1 diabetes mellitus 6, type 1 diabetes mellitus 17, type 1 diabetes mellitus 18, type 1 diabetes mellitus 19, type 1 diabetes mellitus 20, type 1 diabetes mellitus 21, type 1 diabetes mellitus 22, type 1 diabetes mellitus 23, type 1 diabetes mellitus 24

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

7 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 conflicting classifications of pathogenicity, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3596321	NM_000417.3(IL2RA):c.148G>T (p.Glu50Ter)	IL2RA	Likely pathogenic	criteria provided, single submitter
14669	NC_000010.11:g.6072697C>A	IL2RA	Conflicting classifications of pathogenicity	no assertion criteria provided
626117	NM_000417.3(IL2RA):c.584-8del	IL2RA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1021454	NM_000417.3(IL2RA):c.125A>G (p.Lys42Arg)	IL2RA	Uncertain significance	criteria provided, multiple submitters, no conflicts
878604	NM_000417.3(IL2RA):c.655+4C>T	IL2RA	Uncertain significance	criteria provided, multiple submitters, no conflicts
950359	NM_000417.3(IL2RA):c.499G>A (p.Val167Ile)	IL2RA	Uncertain significance	criteria provided, multiple submitters, no conflicts
14670	NC_000010.11:g.6080046T>A	IL2RA	Likely benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · 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
IL2RA	Strong	Autosomal recessive	neonatal diabetes mellitus with congenital hypothyroidism	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL2RA	Orphanet:169100	Immunodeficiency due to CD25 deficiency
IL2RA	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
IL2RA	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis

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
IL2RA	HGNC:6008	ENSG00000134460	P01589	Interleukin-2 receptor subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL2RA	Interleukin-2 receptor subunit alpha	Receptor for interleukin-2.

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
Complement	1	268.0×	0.004

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IL2RA	Complement	yes		Sushi_SCR_CCP_dom, IL-2_rcpt_alpha, Sushi/SCR/CCP_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
caecum	1
lymph node	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL2RA	153	broad	marker	lymph node, vermiform appendix, caecum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL2RA	2,557

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL2RA	P01589	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	1142.0×	0.002	IL2RA
Interleukin-2 signaling	1	951.7×	0.002	IL2RA
Interleukin receptor SHC signaling	1	407.9×	0.003	IL2RA
RAF/MAP kinase cascade	1	61.1×	0.016	IL2RA

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 cell tolerance induction	1	16852.0×	9e-04	IL2RA
regulation of CD4-positive, alpha-beta T cell proliferation	1	8426.0×	9e-04	IL2RA
regulation of T cell homeostatic proliferation	1	5617.3×	9e-04	IL2RA
activation-induced cell death of T cells	1	2407.4×	0.001	IL2RA
interleukin-2-mediated signaling pathway	1	2106.5×	0.001	IL2RA
activated T cell proliferation	1	1872.4×	0.001	IL2RA
inflammatory response to antigenic stimulus	1	936.2×	0.002	IL2RA
positive regulation of activated T cell proliferation	1	674.1×	0.003	IL2RA
positive regulation of T cell differentiation	1	455.5×	0.004	IL2RA
negative regulation of T cell proliferation	1	330.4×	0.005	IL2RA
Notch signaling pathway	1	141.6×	0.010	IL2RA
negative regulation of inflammatory response	1	137.0×	0.010	IL2RA
cell surface receptor signaling pathway	1	64.1×	0.019	IL2RA
immune response	1	47.1×	0.024	IL2RA
inflammatory response	1	37.7×	0.028	IL2RA
apoptotic process	1	28.7×	0.035	IL2RA

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
IL2RA	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
IL2RA	2	Binding:2

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	1	IL2RA
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
IL2RA	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.