GUCA1B

guanylate cyclase activator 1B, the group of EF-hand domain containing

Basic information

Region (hg38): 6:42183283-42194956

Links

ENSG00000112599 ∙ NCBI:2979 ∙ OMIM:602275 ∙ HGNC:4679 ∙ Uniprot:Q9UMX6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 48 (Limited), mode of inheritance: AD
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 48 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 48	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	15452722

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GUCA1B gene.

• not provided (140 variants)
• Retinitis pigmentosa (61 variants)
• Retinitis Pigmentosa, Dominant (18 variants)
• Cone dystrophy (17 variants)
• Inborn genetic diseases (9 variants)
• Retinitis pigmentosa 48 (5 variants)
• not specified (3 variants)
• Leber congenital amaurosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GUCA1B 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			2	28	3	33
missense			68	3	1	72
nonsense			3			3
start loss			1			1
frameshift			4			4
inframe indel			6			6
splice donor/acceptor (+/-2bp)			4			4
splice region			3	4	1	8
non coding			21	29	8	58
Total	0	0	109	60	12

Variants in GUCA1B

This is a list of pathogenic ClinVar variants found in the GUCA1B region.

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

Position	Type	Phenotype	Significance	ClinVar
6-42183497-C-T		Cone dystrophy • Retinitis Pigmentosa, Dominant • Retinitis pigmentosa	Benign/Likely benign (Jan 13, 2018)
6-42183552-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-42183612-A-G		Retinitis Pigmentosa, Dominant • Cone dystrophy • Retinitis pigmentosa	Benign/Likely benign (Jan 13, 2018)
6-42183689-T-C		Retinitis Pigmentosa, Dominant • Cone dystrophy • Retinitis pigmentosa	Benign/Likely benign (Jan 12, 2018)
6-42183727-C-G		Retinitis Pigmentosa, Dominant • Cone dystrophy • Retinitis pigmentosa	Benign/Likely benign (Jan 12, 2018)
6-42183797-G-A		Retinitis pigmentosa	Likely benign (Jan 12, 2018)
6-42183818-G-A		Retinitis pigmentosa	Benign (Jan 12, 2018)
6-42183854-T-G		Retinitis pigmentosa	Benign (Jan 13, 2018)
6-42183875-G-C		Retinitis pigmentosa	Uncertain significance (Jan 15, 2018)
6-42183887-T-C		Retinitis Pigmentosa, Dominant • Cone dystrophy • Retinitis pigmentosa	Benign/Likely benign (Jan 12, 2018)
6-42183947-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
6-42183983-C-T		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
6-42184035-G-A		Retinitis pigmentosa	Benign (Jan 13, 2018)
6-42184048-T-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-42184127-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-42184149-C-A		Retinitis Pigmentosa, Dominant • Cone dystrophy • Retinitis pigmentosa	Benign/Likely benign (Jan 13, 2018)
6-42184197-C-T		Cone dystrophy • Retinitis Pigmentosa, Dominant • Retinitis pigmentosa	Benign/Likely benign (Jan 13, 2018)
6-42184226-A-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-42184234-C-T		Cone dystrophy • Retinitis Pigmentosa, Dominant • Retinitis pigmentosa	Benign/Likely benign (Jan 13, 2018)
6-42184256-A-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-42184308-G-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-42184312-C-T		Cone dystrophy • Retinitis Pigmentosa, Dominant • Retinitis pigmentosa	Benign/Likely benign (Jan 12, 2018)
6-42184313-G-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
6-42184327-G-A		Cone dystrophy • Retinitis Pigmentosa, Dominant • Retinitis pigmentosa	Benign/Likely benign (Jan 13, 2018)
6-42184335-C-T		Cone dystrophy • Retinitis Pigmentosa, Dominant • Retinitis pigmentosa	Benign/Likely benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GUCA1B	protein_coding	protein_coding	ENST00000230361	4	10516

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000213	0.752	125682	0	66	125748	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.224	107	114	0.941	0.00000717	1336
Missense in Polyphen		36	39.34	0.91509		516
Synonymous	-0.715	52	45.8	1.13	0.00000310	354
Loss of Function	1.02	7	10.6	0.662	6.36e-7	104

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000176	0.000176
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000424	0.000422
Middle Eastern	0.000217	0.000217
South Asian	0.000229	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stimulates guanylyl cyclase 1 (GC1) and GC2 when free calcium ions concentration is low, and GC1 and GC2 when free calcium ions concentration is elevated. This Ca(2+)-sensitive regulation of GC is a key event in recovery of the dark state of rod photoreceptors following light exposure.
• Pathway: Phototransduction - Homo sapiens (human);Signaling by GPCR;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: 0.178

Intolerance Scores

• loftool: 0.535
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Haploinsufficiency Scores

• pHI: 0.0942
• hipred: N
• hipred_score: 0.466
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.410

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Guca1b
• Phenotype: vision/eye phenotype

Gene ontology

• Biological process: receptor guanylyl cyclase signaling pathway;cell-cell signaling;body fluid secretion;visual perception;phototransduction;regulation of rhodopsin mediated signaling pathway;positive regulation of guanylate cyclase activity
• Cellular component: photoreceptor inner segment;photoreceptor disc membrane
• Molecular function: calcium ion binding;calcium sensitive guanylate cyclase activator activity