Familial retinal arterial macroaneurysm

Summary

Familial retinal arterial macroaneurysm (MONDO:0013640) is a disease caused by IGFBP7 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Causal gene: IGFBP7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	familial retinal arterial macroaneurysm
Mondo ID	MONDO:0013640
OMIM	614224
Orphanet	284247
ICD-11	800928909
SNOMED CT	764452004
UMLS	C3280205
MedGen	481835
GARD	0012779
Is cancer (heuristic)	no

Also known as: FRAM · Fram · RAMSVPS · retinal arterial macroaneurysm and supravalvular pulmonic stenosis · retinal arterial macroaneurysm with supravalvular pulmonic stenosis

Data availability: 3 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal vascular disorder › familial retinal arterial macroaneurysm

Related subtypes (11): retinal microaneurysm, retinal vascular occlusion, retinal hemangioblastoma, retinal telangiectasia, diabetic retinopathy, retinal vasculitis, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, vasoproliferative tumor of retina, exudative vitreoretinopathy, arteriosclerotic retinopathy, perifoveal exudative vascular anomalous complex

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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1252043	NM_001553.3(IGFBP7):c.829G>A (p.Gly277Ser)	IGFBP7	Pathogenic	no assertion criteria provided
30280	NM_001553.3(IGFBP7):c.830-1G>A	IGFBP7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1299709	NM_001553.3(IGFBP7):c.585+4T>A	IGFBP7	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
IGFBP7	Strong	Autosomal recessive	familial retinal arterial macroaneurysm	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IGFBP7	Orphanet:284247	Familial retinal arterial macroaneurysm

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
IGFBP7	HGNC:5476	ENSG00000163453	Q16270	Insulin-like growth factor-binding protein 7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IGFBP7	Insulin-like growth factor-binding protein 7	Binds IGF1 and IGF2 with a relatively low affinity.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IGFBP7	Antibody/Immunoglobulin	yes		IGFBP-like, Kazal_dom, Ig_sub

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
blood vessel layer	1
renal medulla	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IGFBP7	294	ubiquitous	marker	renal medulla, vena cava, blood vessel layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IGFBP7	1,825

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IGFBP7	Q16270	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Post-translational protein phosphorylation	1	100.2×	0.012	IGFBP7
Senescence-Associated Secretory Phenotype (SASP)	1	99.3×	0.012	IGFBP7
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	IGFBP7

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
response to cortisol	1	1685.2×	0.003	IGFBP7
regulation of steroid biosynthetic process	1	1532.0×	0.003	IGFBP7
cellular response to prostaglandin E stimulus	1	842.6×	0.004	IGFBP7
response to retinoic acid	1	383.0×	0.006	IGFBP7
embryo implantation	1	351.1×	0.006	IGFBP7
regulation of signal transduction	1	267.5×	0.006	IGFBP7
regulation of cell growth	1	221.7×	0.006	IGFBP7
angiogenesis	1	62.4×	0.020	IGFBP7
negative regulation of cell population proliferation	1	42.1×	0.026	IGFBP7
cell adhesion	1	37.5×	0.027	IGFBP7

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
IGFBP7	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	IGFBP7
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)
IGFBP7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.