Microvascular complications of diabetes, susceptibility to, 1

Summary

Microvascular complications of diabetes, susceptibility to, 1 (MONDO:0011386) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microvascular complications of diabetes, susceptibility to, 1
Mondo ID	MONDO:0011386
OMIM	603933
UMLS	C2676832
MedGen	382957
Is cancer (heuristic)	no

Also known as: microvascular complications of diabetes 1 · microvascular complications of diabetes, susceptibility caused by mutation in VEGFA · microvascular complications of diabetes, susceptibility to, 1 · microvascular complications of diabetes, susceptibility to, type 1 · MVCD1 · VEGFA microvascular complications of diabetes, susceptibility

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › microvascular complications of diabetes, susceptibility › microvascular complications of diabetes, susceptibility to, 1

Related subtypes (6): microvascular complications of diabetes, susceptibility to, 2, 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

4 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3593656	NM_003376.6(VEGFA):c.962A>G (p.Lys321Arg)	VEGFA	Uncertain significance	criteria provided, single submitter
3892836	NM_003376.6(VEGFA):c.659T>C (p.Val220Ala)	VEGFA	Uncertain significance	criteria provided, single submitter
3892837	NM_003376.6(VEGFA):c.98G>T (p.Gly33Val)	VEGFA	Uncertain significance	criteria provided, single submitter
12223	NM_003376.6(VEGFA):c.-94C>G	VEGFA	Benign	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
VEGFA	HGNC:12680	ENSG00000112715	P15692	Vascular endothelial growth factor A, long form	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VEGFA	Vascular endothelial growth factor A, long form	Participates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A.

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)
VEGFA	Other/Unknown	no		PDGF/VEGF_dom, PD_growth_factor_CS, VEGF_C

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
left lobe of thyroid gland	1
right lobe of thyroid gland	1
thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VEGFA	297	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VEGFA	167

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VEGFA	P15692	56

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
VEGF ligand-receptor interactions	1	1903.3×	0.003	VEGFA
VEGF binds to VEGFR leading to receptor dimerization	1	1268.9×	0.003	VEGFA
Regulation of gene expression by Hypoxia-inducible Factor	1	951.7×	0.003	VEGFA
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	761.3×	0.003	VEGFA
VEGFR2 mediated cell proliferation	1	571.0×	0.004	VEGFA
Signaling by VEGF	1	219.6×	0.008	VEGFA
VEGFA-VEGFR2 Pathway	1	139.3×	0.010	VEGFA
Potential therapeutics for SARS	1	114.2×	0.011	VEGFA
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.011	VEGFA
Platelet degranulation	1	87.8×	0.011	VEGFA

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
basophil chemotaxis	1	16852.0×	0.002	VEGFA
positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway	1	16852.0×	0.002	VEGFA
coronary vein morphogenesis	1	8426.0×	0.002	VEGFA
obsolete regulation of nitric oxide mediated signal transduction	1	8426.0×	0.002	VEGFA
VEGF-activated neuropilin signaling pathway	1	8426.0×	0.002	VEGFA
cellular stress response to acid chemical	1	8426.0×	0.002	VEGFA
negative regulation of establishment of endothelial barrier	1	8426.0×	0.002	VEGFA
negative regulation of adherens junction organization	1	8426.0×	0.002	VEGFA
lymph vessel morphogenesis	1	5617.3×	0.002	VEGFA
positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	1	5617.3×	0.002	VEGFA
cardiac vascular smooth muscle cell development	1	5617.3×	0.002	VEGFA
positive regulation of lymphangiogenesis	1	5617.3×	0.002	VEGFA
negative regulation of blood-brain barrier permeability	1	5617.3×	0.002	VEGFA
post-embryonic camera-type eye development	1	4213.0×	0.002	VEGFA
positive regulation of protein autophosphorylation	1	4213.0×	0.002	VEGFA
primitive erythrocyte differentiation	1	4213.0×	0.002	VEGFA
regulation of hematopoietic progenitor cell differentiation	1	3370.4×	0.002	VEGFA
vascular endothelial growth factor receptor-2 signaling pathway	1	2808.7×	0.002	VEGFA
positive regulation of epithelial tube formation	1	2808.7×	0.002	VEGFA
positive regulation of blood vessel branching	1	2808.7×	0.002	VEGFA
positive regulation of axon extension involved in axon guidance	1	2407.4×	0.002	VEGFA
positive regulation of mast cell chemotaxis	1	2407.4×	0.002	VEGFA
positive regulation of trophoblast cell migration	1	2407.4×	0.002	VEGFA
tube formation	1	2106.5×	0.002	VEGFA
bone trabecula formation	1	2106.5×	0.002	VEGFA
coronary artery morphogenesis	1	1872.4×	0.002	VEGFA
vascular wound healing	1	1872.4×	0.002	VEGFA
endothelial cell chemotaxis	1	1685.2×	0.002	VEGFA
motor neuron migration	1	1685.2×	0.002	VEGFA
positive regulation of protein localization to early endosome	1	1685.2×	0.002	VEGFA

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
VEGFA	VADADUSTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
VEGFA	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VADADUSTAT	4	VEGFA
BELZUTIFAN	4	VEGFA
OSI-632	2	VEGFA
IZILENDUSTAT	2	VEGFA
IMDATIFAN	2	VEGFA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
VEGFA	64	Binding:64

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

5 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)
VADADUSTAT	4	VEGFA
BELZUTIFAN	4	VEGFA
OSI-632	2	VEGFA
IZILENDUSTAT	2	VEGFA
IMDATIFAN	2	VEGFA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	VEGFA
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.