GUCA1C
protein-codingguanylate cyclase activator 1C, the group of EF-hand domain containing
Gene summary
Predicted to enable calcium ion binding activity and calcium sensitive guanylate cyclase activator activity. Predicted to be involved in regulation of signal transduction. Predicted to be located in photoreceptor disc membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~46.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GUCA1C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005459.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 33 | 3 | 36 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 35 | 3 | 0 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005450.3 | 4 | MANE Select | |
| Ensembl | ENSP00000261047.3 | 4 | MANE Select | |
| RefSeq | NP_001350813.1 | 4 | Standard | |
| Ensembl | ENSP00000377535.3 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Phototransduction - Homo sapiens (human)
- Signaling by GPCR
- Signal Transduction
- Visual signal transduction: Rods
- G alpha (i) signalling events
Biological Process
- signal transduction
- visual perception
- regulation of rhodopsin mediated signaling pathway
- positive regulation of guanylate cyclase activity
Molecular Function
- calcium ion binding
- calcium sensitive guanylate cyclase activator activity
Cellular Component
- photoreceptor disc membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261047
- Coding exons
- 4
- Length
- 46104
- Individuals with no LoFs
- 62931
- Homozygous LoFs
- 11564
- Heterozygous LoFs
- 51215
- Defined
- 125710
- p
- 0.292
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.317 | 116 | 107 | 1.09 | 0.00000484 | 1413 |
| Missense (PolyPhen) | 24 | 22.199 | 1.0811 | 324 | ||
| Synonymous | 0.763 | 33 | 39.1 | 0.845 | 0.00000189 | 361 |
| Loss of Function | -0.669 | 9 | 7.08 | 1.27 | 3.00e-7 | 84 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.27 | 0.27 | notable |
| Latino/Admixed American | 0.34 | 0.34 | notable |
| Ashkenazi Jewish | 0.22 | 0.22 | notable |
| East Asian | 0.16 | 0.16 | notable |
| Finnish | 0.33 | 0.33 | notable |
| European (Non-Finnish) | 0.32 | 0.32 | notable |
| South Asian | 0.24 | 0.24 | notable |
| Other | 0.30 | 0.30 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Stimulates guanylyl cyclase 1 (GC1) and GC2 when free calcium ions concentration is low and inhibits guanylyl cyclases when free calcium ions concentration is elevated. This Ca(2+)- sensitive regulation of guanylyl cyclase (GC) is a key event in recovery of the dark state of rod photoreceptors following light exposure.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.698
- RVIS EVS
- 0.99
- RVIS percentile EVS
- 90.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0242
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | High | Medium | High |