Coats plus syndrome

Summary

Coats plus syndrome (MONDO:0012815) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Cohort genes: 2
• ClinVar variants: 4

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	Coats plus syndrome
Mondo ID	MONDO:0012815
MeSH	C567401
OMIM	612199
Orphanet	313838
SNOMED CT	711482008
UMLS	C2677299
MedGen	383079
GARD	0017412
Is cancer (heuristic)	no

Also known as: cerebroretinal microangiopathy with calcfications and cysts · cerebroretinal microangiopathy with calcifications and cysts · CRMCC

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital vitreoretinal dysplasia › Coats plus syndrome

Related subtypes (8): osteoporosis-pseudoglioma syndrome, Coats disease, incontinentia pigmenti, Norrie disease, spondylo-ocular syndrome, trisomy 13, retinal capillary malformation, persistent hyperplastic primary vitreous

Subtypes (3): cerebroretinal microangiopathy with calcifications and cysts 2, cerebroretinal microangiopathy with calcifications and cysts 1, 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

4 retrieved; paginated sample, class counts are floors:

4 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
31000	NM_025099.6(CTC1):c.2831del (p.Pro944fs)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts
40250	NM_025099.6(CTC1):c.2951GTT[1] (p.Cys985del)	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
843472	NM_025099.6(CTC1):c.3019del (p.Leu1007fs)	CTC1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · 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	Supportive	Autosomal recessive	Coats plus syndrome	6
STN1	Supportive	Autosomal recessive	Coats plus syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTC1	Orphanet:1775	Dyskeratosis congenita
CTC1	Orphanet:313838	Coats plus syndrome
STN1	Orphanet:2032	Idiopathic pulmonary fibrosis
STN1	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
STN1	HGNC:26200	ENSG00000107960	Q9H668	CST complex subunit STN1	gencc

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.
STN1	CST complex subunit STN1	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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTC1	Other/Unknown	no		CTC1, CTC1-like
STN1	Other/Unknown	no		NA-bd_OB_tRNA, NA-bd_OB-fold, Stn1

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
esophagus mucosa	1
lower esophagus mucosa	1
oral cavity	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
STN1	284	ubiquitous	marker	lower esophagus mucosa, oral cavity, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STN1	1,863
CTC1	1,139

Intra-cohort edges

A	B	Sources
CTC1	STN1	biogrid_interaction, intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STN1	Q9H668	8
CTC1	Q2NKJ3	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Telomere C-strand synthesis initiation	2	815.7×	1e-05	CTC1, STN1
Polymerase switching on the C-strand of the telomere	2	423.0×	2e-05	CTC1, STN1
Telomere C-strand (Lagging Strand) Synthesis	1	380.7×	0.006	STN1
Extension of Telomeres	1	300.5×	0.006	STN1
Telomere Maintenance	1	184.2×	0.008	STN1
Chromosome Maintenance	1	105.7×	0.011	STN1
Cell Cycle	1	18.0×	0.055	STN1

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
telomere maintenance via telomere lengthening	2	1872.4×	4e-06	CTC1, STN1
telomere capping	2	1296.3×	4e-06	CTC1, STN1
negative regulation of telomere maintenance via telomerase	2	732.7×	8e-06	CTC1, STN1
positive regulation of DNA replication	2	581.1×	1e-05	CTC1, STN1
telomere maintenance	2	267.5×	4e-05	CTC1, STN1
bone marrow development	1	766.0×	0.003	CTC1
regulation of G2/M transition of mitotic cell cycle	1	648.1×	0.003	CTC1
replicative senescence	1	495.6×	0.004	CTC1
hematopoietic stem cell proliferation	1	324.1×	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
multicellular organism growth	1	68.5×	0.016	CTC1
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: 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
CTC1	0	0
STN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CTC1, STN1

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	—
STN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.