Choroidal dystrophy, central areolar, 1

Summary

Choroidal dystrophy, central areolar, 1 (MONDO:0024539) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 54

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	choroidal dystrophy, central areolar, 1
Mondo ID	MONDO:0024539
OMIM	215500
UMLS	C4551884
MedGen	1639900
GARD	0025420
Is cancer (heuristic)	no

Also known as: CACD1 · central areolar choroidal dystrophy caused by mutation in GUCY2D · choroidal dystrophy, central areolar 1 · choroidal dystrophy, central areolar, 1 · GUCY2D central areolar choroidal dystrophy

Data availability: 54 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › uveal disorder › optic choroid disorder › central areolar choroidal dystrophy › choroidal dystrophy, central areolar, 1

Related subtypes (4): total central choroidal atrophy, partial central choroid dystrophy, choroidal dystrophy, central areolar 2, choroidal dystrophy, central areolar, 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

54 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 13 pathogenic, 8 benign, 7 likely pathogenic, 4 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 3 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070769	NM_000180.4(GUCY2D):c.2476C>T (p.Gln826Ter)	GUCY2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1074833	NM_000180.4(GUCY2D):c.2646C>G (p.Tyr882Ter)	GUCY2D	Pathogenic	criteria provided, multiple submitters, no conflicts
1366687	NM_000180.4(GUCY2D):c.2260G>T (p.Glu754Ter)	GUCY2D	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459421	NM_000180.4(GUCY2D):c.760G>T (p.Glu254Ter)	GUCY2D	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2137915	NM_000180.4(GUCY2D):c.1762C>T (p.Arg588Trp)	GUCY2D	Pathogenic	reviewed by expert panel
2142901	NM_000180.4(GUCY2D):c.2291del (p.Pro764fs)	GUCY2D	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3383016	NM_000180.4(GUCY2D):c.2071del (p.Leu691fs)	GUCY2D	Pathogenic	criteria provided, single submitter
3583120	NM_000180.4(GUCY2D):c.1956+1G>A	GUCY2D	Pathogenic	reviewed by expert panel
560463	NM_000180.4(GUCY2D):c.2303G>A (p.Arg768Gln)	GUCY2D	Pathogenic	reviewed by expert panel
581095	NM_000180.4(GUCY2D):c.3224+1G>C	GUCY2D	Pathogenic	reviewed by expert panel
587413	NM_000180.4(GUCY2D):c.2766C>G (p.Tyr922Ter)	GUCY2D	Pathogenic	reviewed by expert panel
638494	NM_000180.4(GUCY2D):c.1561C>T (p.Arg521Ter)	GUCY2D	Pathogenic	reviewed by expert panel
861651	NM_000180.4(GUCY2D):c.2595del (p.Lys866fs)	GUCY2D	Pathogenic	reviewed by expert panel
9355	NM_000180.4(GUCY2D):c.2512C>T (p.Arg838Cys)	GUCY2D	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98540	NM_000180.4(GUCY2D):c.1343C>A (p.Ser448Ter)	GUCY2D	Pathogenic	reviewed by expert panel
98563	NM_000180.4(GUCY2D):c.2302C>T (p.Arg768Trp)	GUCY2D	Pathogenic	reviewed by expert panel
98602	NM_000180.3(GUCY2D):c.389del (p.Pro130Leufs)	GUCY2D	Pathogenic	reviewed by expert panel
3583118	NM_000180.4(GUCY2D):c.1341dup (p.Ser448fs)	GUCY2D	Likely pathogenic	criteria provided, single submitter
3583119	NM_000180.4(GUCY2D):c.1378+1G>T	GUCY2D	Likely pathogenic	criteria provided, single submitter
3583121	NM_000180.4(GUCY2D):c.2515_2522del (p.Thr839fs)	GUCY2D	Likely pathogenic	criteria provided, single submitter
3583122	NM_000180.4(GUCY2D):c.3127del (p.Thr1043fs)	GUCY2D	Likely pathogenic	criteria provided, single submitter
596790	NM_000180.4(GUCY2D):c.2384G>A (p.Arg795Gln)	GUCY2D	Likely pathogenic	reviewed by expert panel
98581	NM_000180.4(GUCY2D):c.2927G>T (p.Arg976Leu)	GUCY2D	Likely pathogenic	reviewed by expert panel
98590	NM_000180.4(GUCY2D):c.307G>A (p.Glu103Lys)	GUCY2D	Likely pathogenic	reviewed by expert panel
1434751	NM_000180.4(GUCY2D):c.856_876dup (p.Ser286_Leu292dup)	GUCY2D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197118	NM_000180.4(GUCY2D):c.1093C>T (p.Arg365Trp)	GUCY2D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
957041	NM_000180.4(GUCY2D):c.1556C>T (p.Thr519Ile)	GUCY2D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1001416	NM_000180.4(GUCY2D):c.2059C>T (p.His687Tyr)	GUCY2D	Uncertain significance	reviewed by expert panel
1053812	NM_000180.4(GUCY2D):c.131TGC[1] (p.Leu45del)	GUCY2D	Uncertain significance	criteria provided, multiple submitters, no conflicts
1446496	NM_000180.4(GUCY2D):c.2146G>A (p.Asp716Asn)	GUCY2D	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GUCY2D	Orphanet:1872	Cone rod dystrophy
GUCY2D	Orphanet:65	Leber congenital amaurosis
GUCY2D	Orphanet:75377	Central areolar choroidal dystrophy

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
GUCY2D	HGNC:4689	ENSG00000132518	Q02846	Retinal guanylyl cyclase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GUCY2D	Retinal guanylyl cyclase 1	Catalyzes the synthesis of cyclic GMP (cGMP) in rods and cones of photoreceptors.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GUCY2D	Kinase	yes	4.6.1.2	Prot_kinase_dom, A/G_cyclase, Ser-Thr/Tyr_kinase_cat_dom

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
esophagus mucosa	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GUCY2D	121	tissue_specific	marker	buccal mucosa cell, esophagus mucosa, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GUCY2D	1,083

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GUCY2D	Q02846	82.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Inactivation, recovery and regulation of the phototransduction cascade	1	317.2×	0.003	GUCY2D

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
regulation of opsin-mediated signaling pathway	1	1685.2×	0.001	GUCY2D
cGMP biosynthetic process	1	1404.3×	0.001	GUCY2D
receptor guanylyl cyclase signaling pathway	1	1296.3×	0.001	GUCY2D
obsolete cGMP-mediated signaling	1	802.5×	0.002	GUCY2D
visual perception	1	79.5×	0.013	GUCY2D

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
GUCY2D	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GUCY2D	4.6.1.2	guanylate cyclase

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	1	GUCY2D
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)
GUCY2D	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.