GUCA1A
guanylate cyclase activator 1A, the group of EF-hand domain containing
Basic information
Region (hg38): 6:42173364-42181338
Previous symbols: [ "GUCA", "GUCA1", "C6orf131" ]
Links
Phenotypes
GenCC
Source:
- cone dystrophy 3 (Strong), mode of inheritance: AD
- cone dystrophy (Supportive), mode of inheritance: AD
- cone-rod dystrophy (Supportive), mode of inheritance: AD
- central areolar choroidal dystrophy (Supportive), mode of inheritance: AD
- cone dystrophy 3 (Definitive), mode of inheritance: AD
- cone-rod dystrophy 14 (Definitive), mode of inheritance: AD
- hereditary macular dystrophy (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cone dystrophy 3 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Ophthalmologic | 9425234; 15735604; 15953638; 15790869; 19459154; 24024198; 28125083 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (211 variants)
- Cone_dystrophy_3 (38 variants)
- Retinal_dystrophy (20 variants)
- Inborn_genetic_diseases (14 variants)
- Cone-rod_dystrophy_14 (3 variants)
- Cone-rod_dystrophy (3 variants)
- GUCA1A-related_disorder (3 variants)
- not_specified (3 variants)
- Macular_dystrophy (2 variants)
- Retinitis_pigmentosa (2 variants)
- Isolated_macular_dystrophy (1 variants)
- Rod-cone_dystrophy (1 variants)
- See_cases (1 variants)
- Usher_syndrome (1 variants)
- Retinitis_Pigmentosa,_Dominant (1 variants)
- Cone_dystrophy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GUCA1A gene is commonly pathogenic or not. These statistics are base on transcript: NM_001384910.1. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 34 | 36 | ||||
| missense | 27 | 99 | 140 | |||
| nonsense | 5 | |||||
| start loss | 0 | |||||
| frameshift | 7 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 6 | 27 | 113 | 41 | 3 |
Highest pathogenic variant AF is 0.00000273692
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GUCA1A | protein_coding | protein_coding | ENST00000394237 | 4 | 24651 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000414 | 0.659 | 125731 | 0 | 17 | 125748 | 0.0000676 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.369 | 111 | 123 | 0.906 | 0.00000777 | 1345 |
| Missense in Polyphen | 48 | 48.659 | 0.98646 | 595 | ||
| Synonymous | -0.135 | 50 | 48.8 | 1.02 | 0.00000348 | 359 |
| Loss of Function | 0.739 | 6 | 8.30 | 0.723 | 3.65e-7 | 99 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000206 | 0.000206 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000792 | 0.0000791 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Stimulates retinal guanylyl cyclase when free calcium ions concentration is low and inhibits guanylyl cyclase when free calcium ions concentration is elevated (PubMed:19459154). This Ca(2+)-sensitive regulation of retinal guanylyl cyclase is a key event in recovery of the dark state of rod photoreceptors following light exposure. {ECO:0000269|PubMed:19459154, ECO:0000305}.;
- Disease
- DISEASE: Cone dystrophy 3 (COD3) [MIM:602093]: An autosomal dominant cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs. {ECO:0000269|PubMed:11108966, ECO:0000269|PubMed:11146732, ECO:0000269|PubMed:11484154, ECO:0000269|PubMed:15505030, ECO:0000269|PubMed:15735604, ECO:0000269|PubMed:15790869, ECO:0000269|PubMed:19459154, ECO:0000269|PubMed:9425234}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Phototransduction - Homo sapiens (human);Cardiac Hypertrophic Response;Signaling by GPCR;Signal Transduction;visual signal transduction;Visual signal transduction: Rods;G alpha (i) signalling events;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;GPCR downstream signalling;Visual signal transduction: Cones
(Consensus)
Recessive Scores
- pRec
- 0.183
Intolerance Scores
- loftool
- 0.549
- rvis_EVS
- -0.05
- rvis_percentile_EVS
- 49.76
Haploinsufficiency Scores
- pHI
- 0.311
- hipred
- N
- hipred_score
- 0.336
- ghis
- 0.553
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.414
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Guca1a
- Phenotype
- vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Gene ontology
- Biological process
- signal transduction;visual perception;phototransduction;positive regulation of cGMP-mediated signaling;regulation of rhodopsin mediated signaling pathway;positive regulation of guanylate cyclase activity;cellular response to calcium ion
- Cellular component
- photoreceptor inner segment;photoreceptor disc membrane
- Molecular function
- calcium ion binding;calcium sensitive guanylate cyclase activator activity;guanylate cyclase regulator activity