Microvascular complications of diabetes, susceptibility to, 2

Summary

Microvascular complications of diabetes, susceptibility to, 2 (MONDO:0012962) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microvascular complications of diabetes, susceptibility to, 2
Mondo ID	MONDO:0012962
OMIM	612623
UMLS	C2675471
MedGen	436442
Is cancer (heuristic)	no

Also known as: EPO microvascular complications of diabetes, susceptibility · microvascular complications of diabetes 2 · microvascular complications of diabetes, susceptibility caused by mutation in EPO · microvascular complications of diabetes, susceptibility to, 2 · microvascular complications of diabetes, susceptibility to, type 2 · MVCD2

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › microvascular complications of diabetes, susceptibility › microvascular complications of diabetes, susceptibility to, 2

Related subtypes (6): microvascular complications of diabetes, susceptibility to, 1, microvascular complications of diabetes, susceptibility to, 3, 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

1 retrieved; paginated sample, class counts are floors:

1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
16602	NC_000007.14:g.100719675C>A	EPO	risk factor	no assertion criteria provided

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
EPO	Orphanet:247511	Autosomal dominant secondary polycythemia

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
EPO	HGNC:3415	ENSG00000130427	P01588	Erythropoietin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EPO	Erythropoietin	Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass.

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)
EPO	Other/Unknown	no		EPO_TPO, Erythroptn, 4_helix_cytokine-like_core

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
body of pancreas	1
right lobe of liver	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPO	73	tissue_specific	yes	right lobe of liver, triceps brachii, body of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPO	2,945

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPO	P01588	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Erythropoietin activates Phospholipase C gamma (PLCG)	1	1631.4×	0.001	EPO
Erythropoietin activates STAT5	1	1631.4×	0.001	EPO
Signaling by Erythropoietin	1	1038.2×	0.001	EPO
Regulation of gene expression by Hypoxia-inducible Factor	1	951.7×	0.001	EPO
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	951.7×	0.001	EPO
Erythropoietin activates RAS	1	761.3×	0.001	EPO

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 erythrocyte apoptotic process	1	16852.0×	0.002	EPO
negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress	1	4213.0×	0.002	EPO
negative regulation of calcium ion transport into cytosol	1	3370.4×	0.002	EPO
erythropoietin-mediated signaling pathway	1	2808.7×	0.002	EPO
hemoglobin biosynthetic process	1	2808.7×	0.002	EPO
myeloid cell apoptotic process	1	2106.5×	0.003	EPO
response to salt stress	1	1872.4×	0.003	EPO
cellular hyperosmotic response	1	1203.7×	0.003	EPO
response to dexamethasone	1	1203.7×	0.003	EPO
response to hyperoxia	1	1123.5×	0.003	EPO
response to vitamin A	1	1053.2×	0.003	EPO
positive regulation of Ras protein signal transduction	1	887.0×	0.003	EPO
erythrocyte maturation	1	842.6×	0.003	EPO
positive regulation of activated T cell proliferation	1	674.1×	0.003	EPO
response to electrical stimulus	1	648.1×	0.003	EPO
cell surface receptor signaling pathway via STAT	1	561.7×	0.003	EPO
blood circulation	1	510.7×	0.003	EPO
response to axon injury	1	510.7×	0.003	EPO
response to interleukin-1	1	510.7×	0.003	EPO
response to testosterone	1	468.1×	0.004	EPO
acute-phase response	1	421.3×	0.004	EPO
embryo implantation	1	351.1×	0.004	EPO
response to estrogen	1	343.9×	0.004	EPO
erythrocyte differentiation	1	267.5×	0.005	EPO
positive regulation of neuron differentiation	1	198.3×	0.007	EPO
positive regulation of neuron projection development	1	137.0×	0.009	EPO
response to lipopolysaccharide	1	124.8×	0.010	EPO
response to hypoxia	1	95.8×	0.012	EPO
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.013	EPO
positive regulation of cell population proliferation	1	33.6×	0.033	EPO

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

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)
EPO	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.