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7 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GUCA1C
guanylate cyclase activator 1C
Chromosome 3 · 3q13.13
NCBI Gene: 9626Ensembl: ENSG00000138472.11HGNC: HGNC:4680UniProt: C9JNI2
14PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcalcium ion bindingregulation of signal transductioncalcium sensitive guanylate cyclase activator activityneurodegenerative diseasegallbladder diseasesmoking initiationbreast carcinoma
✦AI Summary

GUCA1C encodes GCAP3 (guanylate cyclase-activating protein 3), a cone-specific calcium-binding protein that regulates photoreceptor guanylate cyclases 1. GCAP3 stimulates guanylate cyclases GC1 and GC2 when intracellular calcium is low and inhibits them when calcium is elevated 12, a mechanism critical for recovery of the dark state following light exposure 3. Unlike GCAP1, GCAP3 requires myristoylation for functional activation of GC1, and the protein naturally forms temperature-dependent dimeric aggregates 4. GCAP3 is expressed exclusively in human cone photoreceptors and ciliary epithelium 56. Disease-relevant mutations include the D101H variant associated with retinitis pigmentosa, which abolishes GC1 activation capacity 4, and homozygous nonsense variants (p.Glu18Ter) linked to primary congenital glaucoma with retinal ganglion cell apoptosis 6. Loss of GUCA1C function in knockout zebrafish induces Müller cell gliosis and glaucoma-like retinal damage, indicating roles in both phototransduction and intraocular pressure regulation 6. GUCA1C represents an important candidate gene for hereditary retinal and glaucomatous conditions.

Sources cited
1
GCAP3 structure, stimulates both GC1 and GC2 in low calcium, inhibits at high calcium; located on chromosome 3q13.1
PMID: 10037746
2
GCAPs function as calcium-sensitive regulators; GCAP3 is a third GCAP expressed in humans; mutations in GCAPs associated with dystrophy
PMID: 15336959
3
GCAP3 is one of three GCAPs in vertebrate retina; mediates calcium-dependent activation of retGC for dark state recovery
PMID: 12596930
4
GCAP3 requires myristoylation for GC activation; D101H mutation causes retinitis pigmentosa; GCAP3 forms temperature-dependent aggregates
PMID: 35328663
5
GCAP3 expression exclusively in cone photoreceptors in human retina; expression patterns vary across species
PMID: 11860507
6
GUCA1C nonsense variant (p.Glu18Ter) causes primary congenital glaucoma; GCAP3 detected in ciliary epithelium; knockout causes retinal ganglion cell apoptosis
PMID: 32422965
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.28Weak
gallbladder diseaseOpen Targets
0.28Weak
smoking initiationOpen Targets
0.12Weak
breast carcinomaOpen Targets
0.04Suggestive
attention deficit hyperactivity disorderOpen Targets
0.03Suggestive
substance abuseOpen Targets
0.03Suggestive
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.02Suggestive
pancreatic ductal adenocarcinomaOpen Targets
0.01Suggestive
retinitis pigmentosaOpen Targets
0.01Suggestive
cone dystrophyOpen Targets
0.01Suggestive
pituitary cancerOpen Targets
0.01Suggestive
glaucomaOpen Targets
0.01Suggestive
pancreatic carcinomaOpen Targets
0.01Suggestive
Chorioretinal atrophyOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
congenital glaucomaOpen Targets
0.00Suggestive
gastric carcinomaOpen Targets
0.00Suggestive
primary congenital glaucomaOpen Targets
0.00Suggestive
retinitis pigmentosa 1Open Targets
0.00Suggestive
retinopathyOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RCVRNShared pathway100%CNGB1Protein interaction91%GUCY2FProtein interaction91%GUCY2DProtein interaction91%GUCA1AProtein interaction82%SLC25A18Protein interaction76%
Tissue Expression6 tissues
Heart
100%
Brain
1%
Ovary
0%
Bone Marrow
0%
Lung
0%
Liver
0%
Gene Interaction Network
Click a node to explore
GUCA1CRCVRNCNGB1GUCY2FGUCY2DGUCA1ASLC25A18
PROTEIN STRUCTURE
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PDB2GGZ · 3.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.51LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.78 [0.43–1.51]
RankingsWhere GUCA1C stands among ~20K protein-coding genes
  • #15,883of 20,598
    Most Researched14
  • #15,245of 17,882
    Most Constrained (LOEUF)1.51
Genes detectedGUCA1C
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Molecular Properties of Human Guanylate Cyclase-Activating Protein 3 (GCAP3) and Its Possible Association with Retinitis Pigmentosa.
PMID: 35328663
Int J Mol Sci · 2022
1.00
2
Guanylate cyclase-activating proteins: structure, function, and diversity.
PMID: 15336959
Biochem Biophys Res Commun · 2004
0.86
3
GCAPs: Ca2+-sensitive regulators of retGC.
PMID: 12596930
Adv Exp Med Biol · 2002
0.71
4
Role of
PMID: 32422965
Genes (Basel) · 2020
0.57
5
Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamily.
PMID: 10037746
J Biol Chem · 1999
0.43