Diabetes mellitus, noninsulin-dependent, 1

Summary

Diabetes mellitus, noninsulin-dependent, 1 (MONDO:0011027) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	diabetes mellitus, noninsulin-dependent, 1
Mondo ID	MONDO:0011027
MeSH	C563359
OMIM	601283
UMLS	C1832544
MedGen	321979
GARD	0024769
Is cancer (heuristic)	no

Also known as: diabetes mellitus, noninsulin-dependent 1 · diabetes mellitus, noninsulin-dependent, 1 · diabetes mellitus, noninsulin-dependent, type 1 · NIDDM1

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › endocrine pancreas disorder › diabetes mellitus › type 2 diabetes mellitus › diabetes mellitus, noninsulin-dependent, 1

Related subtypes (5): lipoatrophic diabetes, diabetes mellitus, noninsulin-dependent, 2, diabetes mellitus, noninsulin-dependent, 3, diabetes mellitus, noninsulin-dependent, 4, diabetes mellitus, noninsulin-dependent, 5

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

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4533287	NM_023083.4(CAPN10):c.905G>A (p.Trp302Ter)	CAPN10	Likely pathogenic	criteria provided, single submitter
1704371	NM_023083.4(CAPN10):c.1720C>G (p.Pro574Ala)	CAPN10	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
CAPN10	HGNC:1477	ENSG00000142330	Q9HC96	Calpain-10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CAPN10	Calpain-10	Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CAPN10	Protease	yes	3.4.22.B30	Pept_cys_AS, Peptidase_C2_calpain_cat, Calpain_domain_III

Expression context

Cohort genes with no expression data: 0.

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
apex of heart	1
granulocyte	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CAPN10	195	ubiquitous	yes	apex of heart, right hemisphere of cerebellum, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CAPN10	1,438

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CAPN10	Q9HC96	83.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Degradation of the extracellular matrix	1	117.7×	0.016	CAPN10
Extracellular matrix organization	1	63.1×	0.016	CAPN10

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
cellular component disassembly involved in execution phase of apoptosis	1	8426.0×	5e-04	CAPN10
type B pancreatic cell apoptotic process	1	5617.3×	5e-04	CAPN10
vesicle-mediated transport to the plasma membrane	1	5617.3×	5e-04	CAPN10
positive regulation of type B pancreatic cell apoptotic process	1	2407.4×	9e-04	CAPN10
positive regulation of D-glucose import across plasma membrane	1	455.5×	0.004	CAPN10
positive regulation of insulin secretion	1	255.3×	0.006	CAPN10
cellular response to insulin stimulus	1	170.2×	0.007	CAPN10
regulation of actin cytoskeleton organization	1	157.5×	0.007	CAPN10
proteolysis	1	34.2×	0.029	CAPN10

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
CAPN10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAPN10	3.4.22.B30

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	1	CAPN10
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)
CAPN10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.