Microvascular complications of diabetes, susceptibility to, 7

Summary

Microvascular complications of diabetes, susceptibility to, 7 (MONDO:0012971) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microvascular complications of diabetes, susceptibility to, 7
Mondo ID	MONDO:0012971
OMIM	612635
UMLS	C2673520
MedGen	382123
Is cancer (heuristic)	no

Also known as: microvascular complications of diabetes 7 · microvascular complications of diabetes, susceptibility to, 7 · microvascular complications of diabetes, susceptibility to, type 7 · MVCD7

Data availability: 11 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › microvascular complications of diabetes, susceptibility › microvascular complications of diabetes, susceptibility to, 7

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, 6

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

11 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity; other, 1 conflicting classifications of pathogenicity, 1 conflicting classifications of pathogenicity; other; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065637	NM_000410.4(HFE):c.1006+1G>A	HFE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
407079	NM_000410.4(HFE):c.546_547del (p.Leu183fs)	HFE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10	NM_000410.4(HFE):c.187C>G (p.His63Asp)	HFE	Conflicting classifications of pathogenicity; other	criteria provided, conflicting classifications
11	NM_000410.4(HFE):c.193A>T (p.Ser65Cys)	HFE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
9	NM_000410.4(HFE):c.845G>A (p.Cys282Tyr)	HFE	Conflicting classifications of pathogenicity; other; risk factor	criteria provided, conflicting classifications
222651	NM_000410.4(HFE):c.502G>C (p.Glu168Gln)	HFE	Uncertain significance	criteria provided, multiple submitters, no conflicts
461194	NM_000410.4(HFE):c.766G>A (p.Val256Ile)	HFE	Uncertain significance	criteria provided, multiple submitters, no conflicts
632481	NM_000410.4(HFE):c.676C>T (p.Arg226Trp)	HFE	Uncertain significance	criteria provided, multiple submitters, no conflicts
904398	NM_000410.4(HFE):c.*198C>T	HFE	Uncertain significance	criteria provided, multiple submitters, no conflicts
906791	NM_000410.4(HFE):c.*603C>T	HFE	Uncertain significance	criteria provided, multiple submitters, no conflicts
216425	NM_000410.4(HFE):c.18G>C (p.Arg6Ser)	HFE-AS1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HFE	Orphanet:443057	Sporadic porphyria cutanea tarda
HFE	Orphanet:443062	Familial porphyria cutanea tarda
HFE	Orphanet:465508	Symptomatic form of HFE-related hemochromatosis
HFE	Orphanet:586	Cystic fibrosis
HFE	Orphanet:648581	Digenic hemochromatosis

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HFE	HGNC:4886	ENSG00000010704	Q30201	Hereditary hemochromatosis protein	clinvar
HFE-AS1	HGNC:55168			HFE antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HFE	Hereditary hemochromatosis protein	Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HFE	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
HFE-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 1.

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	1

Top tissues across cohort

Tissue	Cohort genes
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HFE	238	ubiquitous	marker	type B pancreatic cell, olfactory bulb, stromal cell of endometrium
HFE-AS1

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HFE	1,569
HFE-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HFE	Q30201	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Transferrin endocytosis and recycling	1	368.4×	0.003	HFE

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 antigen processing and presentation of endogenous peptide antigen via MHC class I	1	16852.0×	0.001	HFE
regulation of iron ion transport	1	8426.0×	0.001	HFE
response to iron ion starvation	1	5617.3×	0.001	HFE
negative regulation of CD8-positive, alpha-beta T cell activation	1	4213.0×	0.001	HFE
negative regulation of T cell cytokine production	1	2407.4×	0.002	HFE
cellular response to iron ion	1	2407.4×	0.002	HFE
regulation of protein localization to cell surface	1	1685.2×	0.002	HFE
transferrin transport	1	1532.0×	0.002	HFE
urate metabolic process	1	1532.0×	0.002	HFE
positive regulation of peptide hormone secretion	1	1532.0×	0.002	HFE
hormone biosynthetic process	1	1404.3×	0.002	HFE
response to iron ion	1	936.2×	0.002	HFE
negative regulation of ubiquitin-dependent protein catabolic process	1	842.6×	0.002	HFE
positive regulation of receptor-mediated endocytosis	1	802.5×	0.002	HFE
multicellular organismal-level iron ion homeostasis	1	581.1×	0.003	HFE
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	1	401.2×	0.004	HFE
positive regulation of SMAD protein signal transduction	1	383.0×	0.004	HFE
intracellular iron ion homeostasis	1	244.2×	0.005	HFE
receptor-mediated endocytosis	1	221.7×	0.006	HFE
BMP signaling pathway	1	200.6×	0.006	HFE
protein-containing complex assembly	1	113.9×	0.010	HFE
gene expression	1	79.9×	0.014	HFE
cell surface receptor signaling pathway	1	64.1×	0.016	HFE
positive regulation of gene expression	1	38.7×	0.026	HFE

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
HFE	0	0
HFE-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	HFE
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	HFE-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
HFE	0	—
HFE-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.