Microvascular complications of diabetes, susceptibility to, 3

Summary

Microvascular complications of diabetes, susceptibility to, 3 (MONDO:0012963) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 302

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microvascular complications of diabetes, susceptibility to, 3
Mondo ID	MONDO:0012963
OMIM	612624
UMLS	C2675470
MedGen	390806
Is cancer (heuristic)	no

Also known as: ACE microvascular complications of diabetes, susceptibility · microvascular complications of diabetes 3 · microvascular complications of diabetes, susceptibility caused by mutation in ACE · microvascular complications of diabetes, susceptibility to, 3 · microvascular complications of diabetes, susceptibility to, type 3 · MVCD3

Data availability: 302 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › microvascular complications of diabetes, susceptibility › microvascular complications of diabetes, susceptibility to, 3

Related subtypes (6): microvascular complications of diabetes, susceptibility to, 1, microvascular complications of diabetes, susceptibility to, 2, microvascular complications of diabetes, susceptibility to, 4, microvascular complications of diabetes, susceptibility to, 5, microvascular complications of diabetes, susceptibility to, 6, microvascular complications of diabetes, susceptibility to, 7

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

302 retrieved; paginated sample, class counts are floors:

230 uncertain significance, 23 conflicting classifications of pathogenicity, 17 likely pathogenic, 16 benign/likely benign, 6 likely benign, 5 pathogenic/likely pathogenic, 4 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
18063	NM_000789.4(ACE):c.798C>G (p.Tyr266Ter)	ACE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2573840	NM_000789.4(ACE):c.793C>T (p.Arg265Ter)	ACE	Pathogenic	criteria provided, multiple submitters, no conflicts
2712424	NM_000789.4(ACE):c.444_445insTTAGC (p.Arg149fs)	ACE	Pathogenic	criteria provided, multiple submitters, no conflicts
3001305	NM_000789.4(ACE):c.1186C>T (p.Gln396Ter)	ACE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3341107	NM_000789.4(ACE):c.21_30del (p.Arg8fs)	ACE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
50209	NM_000789.4(ACE):c.2371C>T (p.Arg791Ter)	ACE	Pathogenic	criteria provided, multiple submitters, no conflicts
827586	NM_000789.4(ACE):c.1473_1475delinsA (p.Asp491fs)	ACE	Pathogenic	criteria provided, multiple submitters, no conflicts
871758	NM_000789.4(ACE):c.35TGC[1] (p.Leu13_Leu14del)	ACE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1940593	NM_000789.4(ACE):c.232G>T (p.Glu78Ter)	LOC130061383	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1723253	NM_000789.4(ACE):c.1511del (p.Pro504fs)	ACE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1930250	NM_000789.4(ACE):c.945+2T>G	ACE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3234989	NM_000789.4(ACE):c.1342+1G>T	ACE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3582403	NM_000789.4(ACE):c.2T>A (p.Met1Lys)	ACE	Likely pathogenic	criteria provided, single submitter
3582407	NM_000789.4(ACE):c.24_51dup (p.Leu18fs)	ACE	Likely pathogenic	criteria provided, single submitter
3582420	NM_000789.4(ACE):c.250-1G>A	ACE	Likely pathogenic	criteria provided, single submitter
3582436	NM_000789.4(ACE):c.512-2A>G	ACE	Likely pathogenic	criteria provided, single submitter
3582462	NM_000789.4(ACE):c.1126C>T (p.Gln376Ter)	ACE	Likely pathogenic	criteria provided, single submitter
3582475	NM_000789.4(ACE):c.1433dup (p.Phe479fs)	ACE	Likely pathogenic	criteria provided, single submitter
3582481	NM_000789.4(ACE):c.1487+1G>A	ACE	Likely pathogenic	criteria provided, single submitter
3582504	NM_000789.4(ACE):c.1921+328T>C	ACE	Likely pathogenic	criteria provided, single submitter
3582526	NM_000789.4(ACE):c.2306-1G>C	ACE	Likely pathogenic	criteria provided, single submitter
3582534	NM_000789.4(ACE):c.2467dup (p.Asp823fs)	ACE	Likely pathogenic	criteria provided, single submitter
3582545	NM_000789.4(ACE):c.2585_2586del (p.Arg862fs)	ACE	Likely pathogenic	criteria provided, single submitter
3582569	NM_000789.4(ACE):c.3262C>T (p.Gln1088Ter)	ACE	Likely pathogenic	criteria provided, single submitter
3582573	NM_000789.4(ACE):c.3391del (p.Ser1131fs)	ACE	Likely pathogenic	criteria provided, single submitter
559878	NM_000789.4(ACE):c.3503+1G>C	ACE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1219086	NM_000789.4(ACE):c.47_70del (p.Leu16_Pro23del)	ACE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2346883	NM_000789.4(ACE):c.3857G>A (p.Arg1286His)	ACE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2499819	NM_000789.4(ACE):c.776G>A (p.Arg259His)	ACE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2634506	NM_000789.4(ACE):c.59_69del (p.Leu20fs)	ACE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACE	Orphanet:97369	Renal tubular dysgenesis of genetic origin

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
ACE	HGNC:2707	ENSG00000159640	P12821	Angiotensin-converting enzyme	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACE	Angiotensin-converting enzyme	Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte hom…

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)
ACE	Protease	yes	3.4.15.1	Peptidase_M2

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
ileal mucosa	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACE	177	ubiquitous	marker	ileal mucosa, right testis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACE	3,659

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACE	P12821	97

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
Metabolism of Angiotensinogen to Angiotensins	1	634.4×	0.005	ACE
Peptide hormone metabolism	1	271.9×	0.006	ACE
Metabolism of proteins	1	12.4×	0.081	ACE

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
mononuclear cell proliferation	1	16852.0×	8e-04	ACE
regulation of renal output by angiotensin	1	8426.0×	8e-04	ACE
regulation of angiotensin metabolic process	1	8426.0×	8e-04	ACE
cell proliferation in bone marrow	1	8426.0×	8e-04	ACE
negative regulation of gap junction assembly	1	8426.0×	8e-04	ACE
substance P catabolic process	1	5617.3×	9e-04	ACE
regulation of hematopoietic stem cell proliferation	1	5617.3×	9e-04	ACE
antigen processing and presentation of peptide antigen via MHC class I	1	3370.4×	0.001	ACE
regulation of systemic arterial blood pressure by renin-angiotensin	1	3370.4×	0.001	ACE
hormone catabolic process	1	2808.7×	0.001	ACE
bradykinin catabolic process	1	2407.4×	0.001	ACE
regulation of smooth muscle cell migration	1	2407.4×	0.001	ACE
angiotensin-activated signaling pathway	1	1532.0×	0.002	ACE
amyloid-beta metabolic process	1	1532.0×	0.002	ACE
neutrophil mediated immunity	1	1404.3×	0.002	ACE
positive regulation of systemic arterial blood pressure	1	1404.3×	0.002	ACE
angiotensin maturation	1	1296.3×	0.002	ACE
peptide catabolic process	1	1053.2×	0.002	ACE
hormone metabolic process	1	887.0×	0.002	ACE
regulation of vasoconstriction	1	802.5×	0.002	ACE
heart contraction	1	766.0×	0.002	ACE
hematopoietic stem cell differentiation	1	766.0×	0.002	ACE
arachidonate secretion	1	702.2×	0.002	ACE
post-transcriptional regulation of gene expression	1	648.1×	0.002	ACE
blood vessel diameter maintenance	1	624.1×	0.002	ACE
blood vessel remodeling	1	383.0×	0.003	ACE
regulation of heart rate by cardiac conduction	1	374.5×	0.003	ACE
regulation of synaptic plasticity	1	259.3×	0.005	ACE
regulation of blood pressure	1	221.7×	0.005	ACE
male gonad development	1	156.0×	0.007	ACE

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ACE	TELMISARTAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACE	31	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TELMISARTAN	4	ACE
MOEXIPRIL	4	ACE
RAMIPRIL	4	ACE
LISINOPRIL ANHYDROUS	4	ACE
SITAGLIPTIN	4	ACE
TRANDOLAPRIL	4	ACE
CAPTOPRIL	4	ACE
PERINDOPRIL	4	ACE
QUINAPRIL	4	ACE
LOSARTAN	4	ACE
FOSINOPRIL	4	ACE
IMIDAPRIL	4	ACE
ENALAPRILAT ANHYDROUS	4	ACE
ENALAPRIL	4	ACE
BENAZEPRIL	4	ACE
EDETIC ACID	3	ACE
BENAZEPRILAT	2	ACE
MOEXIPRILAT	2	ACE
QUINAPRILAT	2	ACE
OMAPATRILAT	2	ACE
RENTIAPRIL	2	ACE
ZOFENOPRIL	2	ACE
CERONAPRIL	2	ACE
TEPROTIDE	2	ACE
SAMPATRILAT	2	ACE
LIBENZAPRIL	2	ACE
PROLINE	2	ACE
SPIRAPRILAT	2	ACE
FOSINOPRILAT	2	ACE
IMIDAPRILAT	2	ACE

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ACE	304	Binding:288, Functional:8, ADMET:5, Unclassified:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ACE	3.4.15.1	peptidyl-dipeptidase A

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ACE	304

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
TELMISARTAN	4	ACE
MOEXIPRIL	4	ACE
RAMIPRIL	4	ACE
LISINOPRIL ANHYDROUS	4	ACE
SITAGLIPTIN	4	ACE
TRANDOLAPRIL	4	ACE
CAPTOPRIL	4	ACE
PERINDOPRIL	4	ACE
QUINAPRIL	4	ACE
LOSARTAN	4	ACE
FOSINOPRIL	4	ACE
IMIDAPRIL	4	ACE
ENALAPRILAT ANHYDROUS	4	ACE
ENALAPRIL	4	ACE
BENAZEPRIL	4	ACE
EDETIC ACID	3	ACE
BENAZEPRILAT	2	ACE
MOEXIPRILAT	2	ACE
QUINAPRILAT	2	ACE
OMAPATRILAT	2	ACE
RENTIAPRIL	2	ACE
ZOFENOPRIL	2	ACE
CERONAPRIL	2	ACE
TEPROTIDE	2	ACE
SAMPATRILAT	2	ACE
LIBENZAPRIL	2	ACE
PROLINE	2	ACE
SPIRAPRILAT	2	ACE
FOSINOPRILAT	2	ACE
IMIDAPRILAT	2	ACE

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ACE
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	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.