Cerebroretinal microangiopathy with calcifications and cysts 1

Summary

Cerebroretinal microangiopathy with calcifications and cysts 1 (MONDO:0024564) is a disease caused by CTC1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CTC1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 224

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cerebroretinal microangiopathy with calcifications and cysts 1
Mondo ID	MONDO:0024564
OMIM	612199
UMLS	C4552029
MedGen	1636142
GARD	0018441
Is cancer (heuristic)	no

Also known as: cerebroretinal microangiopathy with calcifications and cysts · cerebroretinal microangiopathy with calcifications and cysts 1 · Coats plus syndrome caused by mutation in CTC1 · CRMCC1 · CTC1 Coats plus syndrome

Data availability: 224 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital vitreoretinal dysplasia › Coats plus syndrome › cerebroretinal microangiopathy with calcifications and cysts 1

Related subtypes (2): cerebroretinal microangiopathy with calcifications and cysts 2, cerebroretinal microangiopathy with calcifications and cysts 3

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

224 retrieved; paginated sample, class counts are floors:

104 uncertain significance, 43 conflicting classifications of pathogenicity, 16 pathogenic/likely pathogenic, 15 benign/likely benign, 15 pathogenic, 14 likely pathogenic, 13 benign, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073096	NM_025099.6(CTC1):c.1753C>T (p.Gln585Ter)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322170	NM_025099.6(CTC1):c.2581G>T (p.Glu861Ter)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
1342132	NM_025099.6(CTC1):c.2452C>T (p.Arg818Ter)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452442	NM_025099.6(CTC1):c.1360del (p.Glu454fs)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455096	NM_025099.6(CTC1):c.1683dup (p.Lys562Ter)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
1685681	NM_025099.6(CTC1):c.2346del (p.Leu783fs)	CTC1	Pathogenic	criteria provided, single submitter
2037908	NM_025099.6(CTC1):c.1617+5G>T	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2582454	NM_025099.6(CTC1):c.371_372dup (p.Glu125fs)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
2585520	NM_025099.6(CTC1):c.2176del (p.His726fs)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30995	NM_025099.6(CTC1):c.724_727del (p.Lys242fs)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
30996	NM_025099.6(CTC1):c.2959C>T (p.Arg987Trp)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30998	NM_025099.6(CTC1):c.775G>A (p.Val259Met)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31000	NM_025099.6(CTC1):c.2831del (p.Pro944fs)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
31001	NM_025099.6(CTC1):c.3425T>A (p.Leu1142His)	CTC1	Pathogenic	no assertion criteria provided
31002	NM_025099.6(CTC1):c.1994T>G (p.Val665Gly)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
31003	NM_025099.6(CTC1):c.3583C>T (p.Arg1195Ter)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31004	NM_025099.6(CTC1):c.680C>T (p.Ala227Val)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
31005	NM_025099.6(CTC1):c.1058del (p.Ser353fs)	CTC1	Pathogenic	no assertion criteria provided
40250	NM_025099.6(CTC1):c.2951GTT[1] (p.Cys985del)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
40251	NM_025099.6(CTC1):c.859C>T (p.Arg287Ter)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
434858	NM_025099.6(CTC1):c.1213del (p.Asp405fs)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
529185	NM_025099.6(CTC1):c.2758+1G>T	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
562199	NM_025099.6(CTC1):c.2996dup (p.Pro999_Glu1000insTer)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
576930	NM_025099.6(CTC1):c.1186C>T (p.Arg396Ter)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
647135	NM_025099.6(CTC1):c.2996_2997del (p.Pro999fs)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
653432	NM_025099.6(CTC1):c.248_251dup (p.His84fs)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
840769	NM_025099.6(CTC1):c.2831dup (p.His945fs)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
843472	NM_025099.6(CTC1):c.3019del (p.Leu1007fs)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
862044	NM_025099.6(CTC1):c.1070_1074del (p.Ser357fs)	CTC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
943454	NM_025099.6(CTC1):c.19C>T (p.Gln7Ter)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
CTC1	Definitive	Autosomal recessive	cerebroretinal microangiopathy with calcifications and cysts 1	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTC1	Orphanet:1775	Dyskeratosis congenita
CTC1	Orphanet:313838	Coats plus syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTC1	HGNC:26169	ENSG00000178971	Q2NKJ3	CST complex subunit CTC1	gencc,clinvar
PFAS	HGNC:8863	ENSG00000178921	O15067	Phosphoribosylformylglycinamidine synthase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTC1	CST complex subunit CTC1	Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex.
PFAS	Phosphoribosylformylglycinamidine synthase	Phosphoribosylformylglycinamidine synthase involved in the purines biosynthetic pathway.

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTC1	Other/Unknown	no		CTC1, CTC1-like
PFAS	Enzyme (other)	yes	6.3.5.3	PurL_large, PurM-like_C_dom, Class_I_gatase-like

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar hemisphere	1
granulocyte	1
right hemisphere of cerebellum	1
embryo	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTC1	198	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, cerebellar hemisphere
PFAS	264	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTC1	1,139
PFAS	1,087

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTC1	Q2NKJ3	7
PFAS	O15067	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Purine ribonucleoside monophosphate biosynthesis	1	519.1×	0.004	PFAS
Telomere C-strand synthesis initiation	1	407.9×	0.004	CTC1
Polymerase switching on the C-strand of the telomere	1	211.5×	0.005	CTC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
purine ribonucleoside monophosphate biosynthetic process	1	2808.7×	0.003	PFAS
‘de novo’ IMP biosynthetic process	1	1404.3×	0.003	PFAS
anterior head development	1	1404.3×	0.003	PFAS
‘de novo’ AMP biosynthetic process	1	1053.2×	0.003	PFAS
‘de novo’ XMP biosynthetic process	1	1053.2×	0.003	PFAS
GMP biosynthetic process	1	936.2×	0.003	PFAS
telomere maintenance via telomere lengthening	1	936.2×	0.003	CTC1
bone marrow development	1	766.0×	0.003	CTC1
purine nucleotide biosynthetic process	1	648.1×	0.003	PFAS
L-glutamine metabolic process	1	648.1×	0.003	PFAS
regulation of G2/M transition of mitotic cell cycle	1	648.1×	0.003	CTC1
telomere capping	1	648.1×	0.003	CTC1
replicative senescence	1	495.6×	0.004	CTC1
negative regulation of telomere maintenance via telomerase	1	366.4×	0.004	CTC1
hematopoietic stem cell proliferation	1	324.1×	0.005	CTC1
positive regulation of DNA replication	1	290.6×	0.005	CTC1
spleen development	1	200.6×	0.007	CTC1
thymus development	1	168.5×	0.008	CTC1
positive regulation of fibroblast proliferation	1	147.8×	0.008	CTC1
telomere maintenance	1	133.8×	0.009	CTC1
multicellular organism growth	1	68.5×	0.016	CTC1
response to xenobiotic stimulus	1	34.5×	0.030	PFAS
DNA damage response	1	26.8×	0.037	CTC1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTC1	0	0
PFAS	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
PFAS	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PFAS	6.3.5.3	phosphoribosylformylglycinamidine synthase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	PFAS
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CTC1

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)
CTC1	0	—
PFAS	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.