Cone-rod dystrophy 14

disease

On this page

Also known as CORD14

Summary

Cone-rod dystrophy 14 (MONDO:0800326) is a disease caused by GUCA1A (GenCC Definitive), with 1 cohort gene.

At a glance

Causal gene: GUCA1A (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 14
Mondo ID	MONDO:0800326
GARD	0026503
Is cancer (heuristic)	no

Also known as: CORD14

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › cone-rod dystrophy › cone-rod dystrophy 14

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/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
225232	NM_001384910.1(GUCA1A):c.250C>T (p.Leu84Phe)	GUCA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9152	NM_001384910.1(GUCA1A):c.451C>T (p.Leu151Phe)	GUCA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
225233	NM_001384910.1(GUCA1A):c.320T>C (p.Ile107Thr)	GUCA1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
GUCA1A	Definitive	Autosomal dominant	cone-rod dystrophy 14	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GUCA1A	Orphanet:1871	Progressive cone dystrophy
GUCA1A	Orphanet:1872	Cone rod dystrophy
GUCA1A	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
GUCA1A	HGNC:4678	ENSG00000048545	P43080	Guanylyl cyclase-activating protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GUCA1A	Guanylyl cyclase-activating protein 1	Stimulates retinal guanylyl cyclase when free calcium ions concentration is low and inhibits guanylyl cyclase when free calcium ions concentration is elevated.

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)
GUCA1A	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS

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
hypothalamus	1
nucleus accumbens	1
putamen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GUCA1A	52	broad	marker	nucleus accumbens, putamen, hypothalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GUCA1A	1,434

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GUCA1A	P43080	71.28

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	GUCA1A

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of guanylate cyclase activity	1	16852.0×	4e-04	GUCA1A
obsolete positive regulation of cGMP-mediated signaling	1	2407.4×	0.001	GUCA1A
phototransduction	1	495.6×	0.005	GUCA1A
regulation of signal transduction	1	267.5×	0.007	GUCA1A
cellular response to calcium ion	1	200.6×	0.007	GUCA1A
visual perception	1	79.5×	0.015	GUCA1A
signal transduction	1	16.1×	0.062	GUCA1A

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
GUCA1A	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GUCA1A

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)
GUCA1A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: GUCA1A