Microvascular complications of diabetes, susceptibility to, 6

Summary

Microvascular complications of diabetes, susceptibility to, 6 (MONDO:0012970) 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	microvascular complications of diabetes, susceptibility to, 6
Mondo ID	MONDO:0012970
OMIM	612634
UMLS	C2675128
MedGen	382533
Is cancer (heuristic)	no

Also known as: microvascular complications of diabetes 6 · microvascular complications of diabetes, susceptibility caused by mutation in SOD2 · microvascular complications of diabetes, susceptibility to, 6 · microvascular complications of diabetes, susceptibility to, type 6 · MVCD6 · SOD2 microvascular complications of diabetes, susceptibility

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › microvascular complications of diabetes, susceptibility › microvascular complications of diabetes, susceptibility to, 6

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

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity; risk factor, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
14751	NM_000636.4(SOD2):c.47T>C (p.Val16Ala)	SOD2	Conflicting classifications of pathogenicity; risk factor	no assertion criteria provided
3167444	NM_000636.4(SOD2):c.371A>T (p.Asp124Val)	SOD2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SOD2	Limited	Autosomal dominant	microvascular complications of diabetes, susceptibility to, 6	3

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
SOD2	HGNC:11180	ENSG00000291237	P04179	Superoxide dismutase [Mn], mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SOD2	Superoxide dismutase [Mn], mitochondrial	Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SOD2	Enzyme (other)	yes	1.15.1.1	Mn/Fe_SOD, Mn/Fe_SOD_N, Mn/Fe_SOD_C

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)	0
unknown	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SOD2		ubiquitous

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SOD2	6,580

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SOD2	P04179	48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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
Neurodegenerative Diseases	1	878.5×	0.007	SOD2
Defective Intrinsic Pathway for Apoptosis	1	761.3×	0.007	SOD2
Diseases of programmed cell death	1	634.4×	0.007	SOD2
Mitochondrial unfolded protein response (UPRmt)	1	601.0×	0.007	SOD2
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	1	519.1×	0.007	SOD2
Interleukin-12 family signaling	1	475.8×	0.007	SOD2
Interleukin-12 signaling	1	407.9×	0.007	SOD2
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	380.7×	0.007	SOD2
FOXO-mediated transcription	1	335.9×	0.007	SOD2
Detoxification of Reactive Oxygen Species	1	300.5×	0.007	SOD2
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	300.5×	0.007	SOD2
Transcriptional activation of mitochondrial biogenesis	1	203.9×	0.010	SOD2
Mitochondrial biogenesis	1	167.9×	0.011	SOD2
Cellular response to chemical stress	1	142.8×	0.012	SOD2
Organelle biogenesis and maintenance	1	66.0×	0.023	SOD2
Signaling by Interleukins	1	64.2×	0.023	SOD2
Cytokine Signaling in Immune system	1	40.8×	0.035	SOD2
Cellular responses to stress	1	36.8×	0.036	SOD2
Cellular responses to stimuli	1	31.5×	0.040	SOD2
RNA Polymerase II Transcription	1	22.5×	0.053	SOD2
Gene expression (Transcription)	1	17.8×	0.064	SOD2
Generic Transcription Pathway	1	15.1×	0.072	SOD2
Disease	1	13.1×	0.077	SOD2
Immune System	1	13.0×	0.077	SOD2

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
acetylcholine-mediated vasodilation involved in regulation of systemic arterial blood pressure	1	16852.0×	8e-04	SOD2
erythrophore differentiation	1	16852.0×	8e-04	SOD2
response to magnetism	1	16852.0×	8e-04	SOD2
obsolete positive regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching	1	16852.0×	8e-04	SOD2
negative regulation of membrane hyperpolarization	1	8426.0×	0.001	SOD2
detection of oxygen	1	5617.3×	0.001	SOD2
positive regulation of hydrogen peroxide biosynthetic process	1	4213.0×	0.001	SOD2
response to L-ascorbic acid	1	4213.0×	0.001	SOD2
response to silicon dioxide	1	4213.0×	0.001	SOD2
response to isolation stress	1	4213.0×	0.001	SOD2
response to superoxide	1	3370.4×	0.002	SOD2
response to manganese ion	1	2808.7×	0.002	SOD2
positive regulation of vascular associated smooth muscle cell apoptotic process	1	2106.5×	0.002	SOD2
intracellular oxygen homeostasis	1	1532.0×	0.003	SOD2
response to selenium ion	1	1404.3×	0.003	SOD2
hydrogen peroxide biosynthetic process	1	1404.3×	0.003	SOD2
response to hyperoxia	1	1123.5×	0.003	SOD2
removal of superoxide radicals	1	1053.2×	0.003	SOD2
cellular response to ethanol	1	1053.2×	0.003	SOD2
superoxide metabolic process	1	991.3×	0.003	SOD2
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1	936.2×	0.003	SOD2
intrinsic apoptotic signaling pathway in response to oxidative stress	1	842.6×	0.003	SOD2
respiratory electron transport chain	1	842.6×	0.003	SOD2
response to immobilization stress	1	732.7×	0.003	SOD2
response to cadmium ion	1	732.7×	0.003	SOD2
release of cytochrome c from mitochondria	1	702.2×	0.003	SOD2
superoxide anion generation	1	674.1×	0.003	SOD2
negative regulation of vascular associated smooth muscle cell proliferation	1	674.1×	0.003	SOD2
response to electrical stimulus	1	648.1×	0.003	SOD2
response to zinc ion	1	624.1×	0.003	SOD2

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
SOD2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SOD2	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SOD2	1.15.1.1	superoxide dismutase

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	SOD2
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)
SOD2	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.