GUCY2F

protein-coding

guanylate cyclase 2F, retinal, the group of Transmembrane guanylate cyclases

Gene summary

The protein encoded by this gene is a guanylyl cyclase found predominantly in photoreceptors in the retina. The encoded protein is thought to be involved in resynthesis of cGMP after light activation of the visual signal transduction cascade, allowing a return to the dark state. This protein is a single-pass type I membrane protein. Defects in this gene may be a cause of X-linked retinitis pigmentosa. [provided by RefSeq, Dec 2008]

MANE transcript

NM_001522.3

Inheritance

—

ClinVar variants

U:139B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chrX:109,372,906-109,482,086

External References & Databases

Ensembl (ENSG00000101890)

Transcript & Mutation Effects

hg38 • Region Span ~109.2 kb

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GenCC 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 GUCY2F variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 98

not providedTotal: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001522.3. 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			11 clinvar	4 clinvar	1 clinvar	16
missense			120 clinvar	5 clinvar	4 clinvar	129
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	139	9	5	153

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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_001522.3	RefSeq	NP_001513.2	18	MANE Select
ENST00000218006.3	Ensembl	ENSP00000218006.2	18	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine metabolism - Homo sapiens (human)
Phototransduction - Homo sapiens (human)
Signaling by GPCR
Signal Transduction
Purine metabolism

Biological Process

cGMP biosynthetic process
protein phosphorylation
signal transduction
receptor guanylyl cyclase signaling pathway
visual perception

Molecular Function

peptide receptor activity
guanylate cyclase activity
protein kinase activity
ATP binding
GTP binding

Cellular Component

nuclear outer membrane
plasma membrane
integral component of plasma membrane
photoreceptor disc membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000218006
Coding exons: 18
Length: 109167
Individuals with no LoFs: 125627
Homozygous LoFs: 43
Heterozygous LoFs: 76
Defined: 125746
p: 0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.205	427	415	1.03	0.0000302	7258
Missense (PolyPhen)		134	132.94	1.008		2668
Synonymous	-1.73	178	151	1.18	0.0000108	2175
Loss of Function	1.71	26	37.3	0.697	0.00000301	613

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00092	0.00074	rare
Latino/Admixed American	0.00048	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00066	0.00049	rare
Finnish	0.00069	0.00051	rare
European (Non-Finnish)	0.00082	0.00057	rare
South Asian	0.00043	0.00026	rare
Other	0.00022	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably plays a specific functional role in the rods and/or cones of photoreceptors. It may be the enzyme involved in the resynthesis of cGMP required for recovery of the dark state after phototransduction.;

Recessive Scores

pRec: 0.169

Intolerance Scores

LoFtool: 0.291
RVIS EVS: 1.56
RVIS percentile EVS: 95.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.477

Gene Damage Prediction

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