Type 1 diabetes mellitus 12

Summary

Type 1 diabetes mellitus 12 (MONDO:0011068) 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	type 1 diabetes mellitus 12
Mondo ID	MONDO:0011068
MeSH	C563326
OMIM	601388
DOID	DOID:0110751
UMLS	C1832392
MedGen	318618
Is cancer (heuristic)	no

Also known as: diabetes mellitus, insulin-dependent, 12 · diabetes mellitus, insulin-dependent, type 12 · IDDM12 · insulin-dependent diabetes mellitus 12

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › diabetes mellitus, insulin-dependent, X-linked, susceptibility to › type 1 diabetes mellitus 12

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 15, type 1 diabetes mellitus 6, type 1 diabetes mellitus 10, 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

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
161109	NM_005214.5(CTLA4):c.151C>T (p.Arg51Ter)	CTLA4	Pathogenic	reviewed by expert panel
636389	NM_005214.5(CTLA4):c.457G>A (p.Asp153Asn)	CTLA4	Pathogenic	reviewed by expert panel
432079	NM_005214.5(CTLA4):c.410C>T (p.Pro137Leu)	CTLA4	Likely pathogenic	reviewed by expert panel
430906	NM_005214.5(CTLA4):c.118G>A (p.Val40Met)	CTLA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
574111	NM_005214.5(CTLA4):c.410C>A (p.Pro137Gln)	CTLA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTLA4	Orphanet:2584	Classic mycosis fungoides
CTLA4	Orphanet:3162	Sézary syndrome
CTLA4	Orphanet:391490	Adult-onset myasthenia gravis
CTLA4	Orphanet:436159	Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency
CTLA4	Orphanet:536	Systemic lupus erythematosus
CTLA4	Orphanet:900	Granulomatosis with polyangiitis

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
CTLA4	HGNC:2505	ENSG00000163599	P16410	Cytotoxic T-lymphocyte protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTLA4	Cytotoxic T-lymphocyte protein 4	Inhibitory receptor acting as a major negative regulator of T-cell responses.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTLA4	Antibody/Immunoglobulin	yes		Ig_sub, CTLA4, Ig_V-set

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
buccal mucosa cell	1
lymph node	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTLA4	164	tissue_specific	marker	lymph node, vermiform appendix, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTLA4	3,863

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTLA4	P16410	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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×	0.003	CTLA4
Co-inhibition by CTLA4	1	519.1×	0.003	CTLA4
Co-stimulation by CD28	1	380.7×	0.003	CTLA4

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
negative regulation of regulatory T cell differentiation	1	3370.4×	0.003	CTLA4
negative regulation of B cell proliferation	1	936.2×	0.006	CTLA4
negative regulation of T cell activation	1	526.6×	0.006	CTLA4
B cell receptor signaling pathway	1	401.2×	0.006	CTLA4
negative regulation of T cell receptor signaling pathway	1	366.4×	0.006	CTLA4
negative regulation of T cell proliferation	1	330.4×	0.006	CTLA4
T cell receptor signaling pathway	1	151.8×	0.010	CTLA4
adaptive immune response	1	84.3×	0.016	CTLA4
positive regulation of apoptotic process	1	56.7×	0.021	CTLA4
DNA damage response	1	53.5×	0.021	CTLA4
immune response	1	47.1×	0.021	CTLA4

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
CTLA4	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
CTLA4	1	Binding:1

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	CTLA4
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)
CTLA4	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.