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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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GUCA1A
guanylate cyclase activator 1A
Chromosome 6 Β· 6p21.1
NCBI Gene: 2978Ensembl: ENSG00000048545.18HGNC: HGNC:4678UniProt: P43080
58PubMed Papers
22Diseases
0Drugs
6Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
guanylate cyclase regulator activitycone photoreceptor outer segmentprotein bindingphotoreceptor inner segmentcone dystrophy 3Cone rod dystrophyProgressive cone dystrophycone-rod dystrophy
✦AI Summary

GUCA1A encodes guanylate cyclase-activating protein 1 (GCAP1), a calcium-sensitive regulator of retinal guanylyl cyclase critical for photoreceptor function. GCAP1 stimulates guanylyl cyclase when intracellular calcium is low and inhibits it when calcium rises, enabling recovery of the dark state in rod photoreceptors following light exposure 1234. This calcium-dependent regulation of cyclic GMP levels is essential for normal phototransduction 5. GUCA1A mutations cause autosomal dominant cone dystrophy 3 (COD3) and cone-rod dystrophy 14, characterized by progressive central vision loss and color vision defects typically onset in the third to fifth decade 67. Disease pathology involves altered rather than loss of GCAP1 function; mouse models carrying disease mutations show abnormal cGMP accumulation preceding photoreceptor degeneration, with cone dysfunction predominating over rod involvement 8. Clinical presentations show substantial intrafamilial heterogeneity, with specific variants conferring different severity profiles: p.(Tyr99Cys) is most common, while p.(Glu111Ala) associates with worse vision and p.(Leu84Phe) with earlier-onset disease 7. Electrophysiology typically reveals cone dystrophy patterns with variable rod involvement 9. GUCA1A variants account for a small proportion of inherited retinal disease cases 1011.

Sources cited
1
GCAP1 stimulates guanylyl cyclase at low calcium and inhibits at high calcium
PMID: 18706439
2
Calcium-sensitive regulation of guanylyl cyclase by GCAP1
PMID: 19459154
3
GCAP1 calcium-dependent function in phototransduction
PMID: 30184081
4
GCAP1 role in dark state recovery
PMID: 30622141
5
GUCA1A encodes phototransduction protein involved in inherited retinal disease
PMID: 40013354
6
GUCA1A mutations cause cone, cone-rod, and macular dystrophy with onset in third-fifth decade
PMID: 15953638
7
GUCA1A mutations impair GCAP1 function; disease involves cGMP accumulation and cone-predominant photoreceptor degeneration
PMID: 21464903
8
GUCA1A-associated retinopathy shows progressive visual loss; different variants associate with variable severity
PMID: 39969478
9
GUCA1A mutations cause cone dystrophy with generalized cone dysfunction
PMID: 24875811
10
GUCA1A mutations identified in cone/cone-rod dystrophy cohort
PMID: 29555955
11
GUCA1A associated with cone and cone-rod dystrophies in comprehensive IRD review
PMID: 38278208
Disease Associationsβ“˜22
cone dystrophy 3Open Targets
0.83Strong
Cone rod dystrophyOpen Targets
0.76Strong
Progressive cone dystrophyOpen Targets
0.71Strong
cone-rod dystrophyOpen Targets
0.59Moderate
cone-rod dystrophy 14Open Targets
0.55Moderate
Retinal dystrophyOpen Targets
0.54Moderate
Macular dystrophyOpen Targets
0.49Moderate
Rod-cone dystrophyOpen Targets
0.46Moderate
central areolar choroidal dystrophyOpen Targets
0.38Weak
cone dystrophyOpen Targets
0.38Weak
eye diseaseOpen Targets
0.37Weak
hereditary macular dystrophyOpen Targets
0.37Weak
retinitis pigmentosaOpen Targets
0.35Weak
retinopathyOpen Targets
0.34Weak
isolated macular dystrophyOpen Targets
0.34Weak
Usher syndromeOpen Targets
0.33Weak
neuroinflammatory disorderOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
phototoxic dermatitisOpen Targets
0.08Suggestive
age-related macular degenerationOpen Targets
0.07Suggestive
Cone dystrophy 3UniProt
Cone-rod dystrophy 14UniProt
Pathogenic Variants6
NM_001384910.1(GUCA1A):c.256G>A (p.Gly86Arg)Likely pathogenic
not provided|Cone dystrophy 3
β˜…β˜…β˜†β˜†2025β†’ Residue 86
NM_001384910.1(GUCA1A):c.312C>G (p.Asn104Lys)Pathogenic
not provided|Cone dystrophy 3
β˜…β˜…β˜†β˜†2024β†’ Residue 104
NM_001384910.1(GUCA1A):c.300T>G (p.Asp100Glu)Pathogenic
Cone dystrophy 3
β˜…β˜†β˜†β˜†2024β†’ Residue 100
NM_001384910.1(GUCA1A):c.332A>G (p.Glu111Gly)Likely pathogenic
Cone dystrophy 3
β˜…β˜†β˜†β˜†2023β†’ Residue 111
NM_001384910.1(GUCA1A):c.295T>C (p.Tyr99His)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 99
NM_001384910.1(GUCA1A):c.428delinsCACA (p.Ile143delinsThrHis)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 143
View on ClinVar β†—
Related Genes
GUCY2FProtein interaction98%RD3Protein interaction84%GUF1Protein interaction83%GUCA1CProtein interaction82%GUCY2DProtein interaction80%CABP1Protein interaction79%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
35%
Liver
12%
Ovary
0%
Lung
0%
Heart
0%
Gene Interaction Network
Click a node to explore
GUCA1AGUCY2FRD3GUF1GUCA1CGUCY2DCABP1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P43080
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.07LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.69 [0.45–1.07]
RankingsWhere GUCA1A stands among ~20K protein-coding genes
  • #7,872of 20,598
    Most Researched58
  • #3,385of 5,498
    Most Pathogenic Variants6
  • #10,818of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedGUCA1A
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy.
PMID: 29555955
Sci Rep Β· 2018
1.00
2
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
PMID: 38278208
Prog Retin Eye Res Β· 2024
0.90
3
Monogenic Retinal Diseases Associated With Genes Encoding Phototransduction Proteins: A Review.
PMID: 40013354
Clin Exp Ophthalmol Β· 2025
0.80
4
Mutation in the gene GUCA1A, encoding guanylate cyclase-activating protein 1, causes cone, cone-rod, and macular dystrophy.
PMID: 15953638
Ophthalmology Β· 2005
0.70
5
Dominant cone-rod dystrophy: a mouse model generated by gene targeting of the GCAP1/Guca1a gene.
PMID: 21464903
PLoS One Β· 2011
0.60