Microvascular complications of diabetes, susceptibility to, 4

Summary

Microvascular complications of diabetes, susceptibility to, 4 (MONDO:0012966) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microvascular complications of diabetes, susceptibility to, 4
Mondo ID	MONDO:0012966
OMIM	612628
UMLS	C2675112
MedGen	382527
Is cancer (heuristic)	no

Also known as: IL1RN microvascular complications of diabetes, susceptibility · microvascular complications of diabetes 4 · microvascular complications of diabetes, susceptibility caused by mutation in IL1RN · microvascular complications of diabetes, susceptibility to, 4 · microvascular complications of diabetes, susceptibility to, type 4 · MVCD4

Data availability: 7 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › microvascular complications of diabetes, susceptibility › microvascular complications of diabetes, susceptibility to, 4

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, 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

7 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 1 pathogenic; risk factor, 1 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
14674	NM_173842.3(IL1RN):c.206-516ATCCTGGGGAAAGTGAGGGAAATATGGACATCACATGGAACAACATCCAGGAGACTCAGGCCTCTAGGAGTAACTGGGTAGTGTGC[2]	IL1RN	Pathogenic; risk factor	no assertion criteria provided
1015756	NM_173842.3(IL1RN):c.212T>C (p.Ile71Thr)	IL1RN	Uncertain significance	criteria provided, multiple submitters, no conflicts
572109	NM_173841.3(IL1RN):c.58A>C (p.Asn20His)	IL1RN	Uncertain significance	criteria provided, multiple submitters, no conflicts
827981	NM_173842.3(IL1RN):c.68C>T (p.Thr23Met)	IL1RN	Uncertain significance	criteria provided, multiple submitters, no conflicts
944477	NM_173842.3(IL1RN):c.496G>A (p.Val166Ile)	IL1RN	Uncertain significance	criteria provided, multiple submitters, no conflicts
1572045	NM_173842.3(IL1RN):c.300G>A (p.Glu100=)	IL1RN	Likely benign	criteria provided, multiple submitters, no conflicts
330823	NM_173842.3(IL1RN):c.69G>A (p.Thr23=)	IL1RN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
IL1RN	Orphanet:210115	Sterile multifocal osteomyelitis with periostitis and pustulosis

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
IL1RN	HGNC:6000	ENSG00000136689	P18510	Interleukin-1 receptor antagonist protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL1RN	Interleukin-1 receptor antagonist protein	Anti-inflammatory antagonist of interleukin-1 family of proinflammatory cytokines such as interleukin-1beta/IL1B and interleukin-1alpha/IL1A.

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)
IL1RN	Other/Unknown	no		IL-1_fam, IL-1RA/IL-36, IL1/FGF

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
buccal mucosa cell	1
lower esophagus mucosa	1
palpebral conjunctiva	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL1RN	220	broad	marker	lower esophagus mucosa, buccal mucosa cell, palpebral conjunctiva

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL1RN	2,550

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL1RN	P18510	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Interleukin-10 signaling	1	233.1×	0.008	IL1RN
Interleukin-1 signaling	1	124.1×	0.008	IL1RN

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 heterotypic cell-cell adhesion	1	1872.4×	0.002	IL1RN
negative regulation of interleukin-1-mediated signaling pathway	1	1685.2×	0.002	IL1RN
insulin secretion	1	432.1×	0.005	IL1RN
acute-phase response	1	421.3×	0.005	IL1RN
response to glucocorticoid	1	324.1×	0.005	IL1RN
lipid metabolic process	1	91.6×	0.015	IL1RN
immune response	1	47.1×	0.024	IL1RN
inflammatory response	1	37.7×	0.027	IL1RN

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
IL1RN	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
IL1RN	26	Binding:26

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	IL1RN

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)
IL1RN	26	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.