GUCA1B

protein-coding

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

Gene summary

The protein encoded by this gene is a calcium-binding protein that activates photoreceptor guanylate cyclases. This gene may have arisen due to a gene duplication event since there is a highly similar gene clustered with it on chromosome 6. Mutations in this gene can cause a form of retinitis pigmentosa. [provided by RefSeq, Nov 2009]

MANE transcript

NM_002098.6

Inheritance

ClinVar variants

U:111B:53

Top phenotype

Retinitis pigmentosa 48

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr6:42,183,284-42,194,956

External References & Databases

Ensembl (ENSG00000112599)

Transcript & Mutation Effects

hg38 • Region Span ~11.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

retinitis pigmentosa 48LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013447

Submitter: Ambry Genetics

retinitis pigmentosa 48LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013447

Submitter: G2P

retinitis pigmentosaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019200

Submitter: Orphanet

retinitis pigmentosa 48STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013447

Submitter: Labcorp Genetics (formerly Invitae)

retinitis pigmentosa 48MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0013447

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Retinitis pigmentosa 48AD

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 15452722

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GUCA1B variants in ClinVar

7 Conditions Cataloged

not providedTotal: 168

not specifiedTotal: 31

Retinal dystrophyTotal: 17

Retinitis pigmentosaTotal: 11

Retinitis pigmentosa 48Total: 6

GUCA1B-related conditionTotal: 2

Leber congenital amaurosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002098.6. 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			1 clinvar	43 clinvar	2 clinvar	46
missense			94 clinvar	7 clinvar	1 clinvar	102
nonsense			5 clinvar			5
start loss			1 clinvar			1
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	111	50	3	164

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002098.6	RefSeq	NP_002089.4	4	MANE Select
ENST00000230361.4	Ensembl	ENSP00000230361.3	4	MANE Select

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

receptor guanylyl cyclase signaling pathway
cell-cell signaling
body fluid secretion
visual perception
phototransduction

Molecular Function

calcium ion binding
calcium sensitive guanylate cyclase activator activity

Cellular Component

photoreceptor inner segment
photoreceptor disc membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000230361
Coding exons: 4
Length: 10516
Individuals with no LoFs: 125682
Homozygous LoFs: 0
Heterozygous LoFs: 66
Defined: 125748
p: 0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.224	107	114	0.941	0.00000717	1336
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00042	0.00042	rare
South Asian	0.00023	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.178

Intolerance Scores

LoFtool: 0.535
RVIS EVS: 0.04
RVIS percentile EVS: 56.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.410

Gene Damage Prediction

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