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

ENSG00000048545 ∙ NCBI:2978 ∙ OMIM:600364 ∙ HGNC:4678 ∙ Uniprot:P43080 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the GUCA1A gene.

• not provided (5 variants)
• Cone dystrophy 3 (4 variants)
• Retinal dystrophy (2 variants)
• Retinitis pigmentosa (1 variants)
• Macular 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				28	2	30
missense	6	14	87	3		110
nonsense			4			4
start loss						0
frameshift			7			7
inframe indel		2	4			6
splice donor/acceptor (+/-2bp)			2			2
splice region			4	7		11
non coding			11	26	7	44
Total	6	16	115	57	9

Variants in GUCA1A

This is a list of pathogenic ClinVar variants found in the GUCA1A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-42173372-C-T		Cone dystrophy 3	Uncertain significance (Jan 13, 2018)
6-42173526-G-A		Cone dystrophy 3	Uncertain significance (Jan 13, 2018)
6-42173531-G-A		Cone dystrophy 3	Benign (Jan 13, 2018)
6-42173588-A-G		Cone dystrophy 3	Benign (Jul 05, 2018)
6-42173619-C-T			Likely benign (Nov 28, 2022)
6-42173622-C-G			Uncertain significance (Sep 12, 2022)
6-42173622-C-T		not specified • Cone dystrophy 3	Benign/Likely benign (Jan 25, 2024)
6-42173623-G-A		Cone dystrophy 3	Conflicting classifications of pathogenicity (Nov 06, 2023)
6-42173624-T-C			Uncertain significance (Jun 11, 2022)
6-42173633-G-C			Uncertain significance (Jan 08, 2024)
6-42173638-T-C			Uncertain significance (Jun 24, 2021)
6-42173640-A-C			Likely benign (Sep 05, 2023)
6-42173642-TGGAGGA-T			Uncertain significance (Jan 18, 2017)
6-42173654-G-C		Retinal dystrophy	Uncertain significance (Aug 28, 2018)
6-42173661-C-T			Benign (Oct 13, 2023)
6-42173662-G-A			Uncertain significance (Nov 18, 2023)
6-42173662-G-T			Uncertain significance (Jun 18, 2023)
6-42173673-G-A			Likely benign (Jun 30, 2023)
6-42173674-T-TC			Uncertain significance (Jul 12, 2021)
6-42173677-T-C			Uncertain significance (Sep 27, 2023)
6-42173679-C-A			Uncertain significance (Dec 22, 2023)
6-42173685-GTTC-G			Uncertain significance (Apr 09, 2021)
6-42173698-T-C			Uncertain significance (Nov 24, 2022)
6-42173699-G-A			Uncertain significance (Sep 01, 2022)
6-42173699-GC-G			Uncertain significance (Apr 07, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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