GUCY2D

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

Basic information

Region (hg38): 17:8002615-8020342

Previous symbols: [ "CORD6", "LCA", "GUC2D", "GUC1A4" ]

Links

ENSG00000132518 ∙ NCBI:3000 ∙ OMIM:600179 ∙ HGNC:4689 ∙ Uniprot:Q02846 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber congenital amaurosis 1 (Definitive), mode of inheritance: AR
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• central areolar choroidal dystrophy (Supportive), mode of inheritance: AD
• cone-rod dystrophy 6 (Strong), mode of inheritance: AD
• Leber congenital amaurosis 1 (Strong), mode of inheritance: AR
• night blindness, congenital stationary, type1i (Strong), mode of inheritance: AR
• GUCY2D-related dominant retinopathy (Definitive), mode of inheritance: AD
• GUCY2D-related recessive retinopathy (Definitive), mode of inheritance: AR
• cone-rod dystrophy (Definitive), mode of inheritance: AD
• central areolar choroidal dystrophy (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Choroidal dystrophy, central areolar 1; Cone-rod dystrophy 6; Leber congenital amaurosis, type 1; Cone-Rod dystrophy, autosomal recessive; Night blindness, congenital stationary, type 1I	AD/AR	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	8554074; 9097965; 9618177; 11709018; 12015276; 12325031; 12623820; 12552567; 15024725; 20006823; 20301475; 20517349; 22194653; 22695961; 29559409

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GUCY2D gene.

• Cone-rod dystrophy 6;Leber congenital amaurosis 1 (56 variants)
• Leber congenital amaurosis 1 (30 variants)
• Leber congenital amaurosis 1;Cone-rod dystrophy 6 (26 variants)
• GUCY2D-related recessive retinopathy (22 variants)
• not provided (19 variants)
• Retinal dystrophy (13 variants)
• Cone-rod dystrophy 6 (7 variants)
• Leber congenital amaurosis (6 variants)
• GUCY2D-related disorder (4 variants)
• Night blindness, congenital stationary, type1i (3 variants)
• Cone-rod dystrophy 6;Leber congenital amaurosis 1;Choroidal dystrophy, central areolar, 1;Night blindness, congenital stationary, type1i (2 variants)
• Cone-rod dystrophy 6;Choroidal dystrophy, central areolar, 1;Leber congenital amaurosis 1;Night blindness, congenital stationary, type1i (2 variants)
• Choroidal dystrophy, central areolar, 1;Cone-rod dystrophy 6;Night blindness, congenital stationary, type1i;Leber congenital amaurosis 1 (2 variants)
• Choroidal dystrophy, central areolar, 1 (2 variants)
• Cone-rod dystrophy (2 variants)
• Leber congenital amaurosis 1;Night blindness, congenital stationary, type1i;Choroidal dystrophy, central areolar, 1;Cone-rod dystrophy 6 (2 variants)
• Congenital blindness (1 variants)
• POLR3-related leukodystrophy (1 variants)
• Leber congenital amaurosis 1;Choroidal dystrophy, central areolar, 1;Cone-rod dystrophy 6;Night blindness, congenital stationary, type1i (1 variants)
• not specified (1 variants)
• Night blindness, congenital stationary, type1i;Leber congenital amaurosis 1;Cone-rod dystrophy 6;Choroidal dystrophy, central areolar, 1 (1 variants)
• Night blindness, congenital stationary, type1i;Choroidal dystrophy, central areolar, 1;Cone-rod dystrophy 6;Leber congenital amaurosis 1 (1 variants)
• Optic atrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GUCY2D 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			7	381	8	396
missense	17	27	477	15	8	544
nonsense	30	6				36
start loss	4	1				5
frameshift	44	16				60
inframe indel		3	8		1	12
splice donor/acceptor (+/-2bp)	9	14	2			25
splice region			22	52	4	78
non coding			3	153	17	173
Total	104	67	497	549	34

Highest pathogenic variant AF is 0.000341

Variants in GUCY2D

This is a list of pathogenic ClinVar variants found in the GUCY2D region.

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

Position	Type	Phenotype	Significance	ClinVar
17-8002739-A-G			Benign (Jun 19, 2021)
17-8002911-C-T		GUCY2D-related disorder	Likely benign (Jul 04, 2019)
17-8003044-GGCAAT-G		Cone-rod dystrophy 6;Leber congenital amaurosis 1	Pathogenic (Jan 10, 2024)
17-8003048-A-G		Leber congenital amaurosis 1 • Cone-rod dystrophy 6;Leber congenital amaurosis 1	Pathogenic (Dec 03, 2023)
17-8003049-T-A		Leber congenital amaurosis 1	Pathogenic (-)
17-8003049-T-C		Retinal dystrophy	Likely pathogenic (May 27, 2024)
17-8003050-G-A		Leber congenital amaurosis 1 • GUCY2D-related recessive retinopathy	Pathogenic (Jan 30, 2025)
17-8003050-G-C		Leber congenital amaurosis 1 • Leber congenital amaurosis 1;Cone-rod dystrophy 6	Pathogenic (Oct 18, 2023)
17-8003054-G-T		Retinal dystrophy	Uncertain significance (Jan 01, 2023)
17-8003058-G-A		Leber congenital amaurosis 1;Cone-rod dystrophy 6	Benign (Jan 29, 2024)
17-8003058-GCGCC-G		Cone-rod dystrophy 6;Leber congenital amaurosis 1	Pathogenic (Nov 18, 2022)
17-8003060-G-A		Cone-rod dystrophy 6;Leber congenital amaurosis 1	Uncertain significance (Oct 30, 2020)
17-8003063-C-T		Cone-rod dystrophy 6;Leber congenital amaurosis 1 • Inborn genetic diseases	Uncertain significance (Nov 20, 2024)
17-8003071-G-T		Cone-rod dystrophy 6;Leber congenital amaurosis 1	Likely benign (Sep 11, 2023)
17-8003083-G-A		Leber congenital amaurosis 1;Cone-rod dystrophy 6	Likely benign (Oct 19, 2023)
17-8003087-C-A		Leber congenital amaurosis 1;Cone-rod dystrophy 6	Uncertain significance (Jun 04, 2023)
17-8003087-C-G		Choroidal dystrophy, central areolar, 1 • Cone-rod dystrophy 6;Leber congenital amaurosis 1	Uncertain significance (Jul 07, 2023)
17-8003089-C-T		Leber congenital amaurosis 1;Cone-rod dystrophy 6	Likely benign (Sep 24, 2023)
17-8003092-G-T		Cone-rod dystrophy 6;Leber congenital amaurosis 1	Likely benign (Feb 09, 2023)
17-8003093-C-T		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
17-8003096-T-C		Cone-rod dystrophy 6;Leber congenital amaurosis 1 • Cone-rod dystrophy 6;Night blindness, congenital stationary, type1i;Leber congenital amaurosis 1;Choroidal dystrophy, central areolar, 1	Uncertain significance (Oct 05, 2022)
17-8003098-C-A		Cone-rod dystrophy 6;Leber congenital amaurosis 1	Pathogenic (Mar 09, 2023)
17-8003098-C-CGGTCCCGCGTGGTGGGCTCCGTCCCTGCCCCGCCTCCCCCGGGCCCTG		Leber congenital amaurosis 1	Likely pathogenic (-)
17-8003101-T-G		Cone-rod dystrophy 6;Leber congenital amaurosis 1	Likely benign (Nov 25, 2023)
17-8003104-C-G		Leber congenital amaurosis 1;Cone-rod dystrophy 6	Likely benign (May 02, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GUCY2D	protein_coding	protein_coding	ENST00000254854	18	17746

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.46e-10	0.998	125591	0	157	125748	0.000624

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.781	598	654	0.914	0.0000449	6880
Missense in Polyphen		217	274.73	0.78986		2975
Synonymous	-0.616	301	288	1.05	0.0000205	2455
Loss of Function	2.86	22	42.0	0.524	0.00000224	455

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000664	0.000661
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00392	0.00380
European (Non-Finnish)	0.000448	0.000440
Middle Eastern	0.0000544	0.0000544
South Asian	0.000132	0.000131
Other	0.000689	0.000652

dbNSFP

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.
• Disease: DISEASE: Cone-rod dystrophy 6 (CORD6) [MIM:601777]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:12552567, ECO:0000269|PubMed:15111605, ECO:0000269|PubMed:18332321, ECO:0000269|PubMed:18487367, ECO:0000269|PubMed:20517349, ECO:0000269|PubMed:21552474, ECO:0000269|PubMed:22194653, ECO:0000269|PubMed:23734073, ECO:0000269|PubMed:24480840, ECO:0000269|PubMed:9618177, ECO:0000269|PubMed:9683616}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Choroidal dystrophy, central areolar, 1 (CACD1) [MIM:215500]: A form of central areolar choroidal dystrophy, a retinal disease that affects the macula and results in a well- demarcated circumscribed area of atrophy of the pigment epithelium and choriocapillaris. CACD1 inheritance is autosomal recessive. {ECO:0000269|PubMed:22695961}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Purine metabolism - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);Phototransduction - Homo sapiens (human);Signaling by GPCR;Signal Transduction;Purine metabolism;actions of nitric oxide in the heart;Purine nucleotides nucleosides metabolism;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: 0.105

Intolerance Scores

• loftool: 0.0925
• rvis_EVS: -1.37
• rvis_percentile_EVS: 4.51

Haploinsufficiency Scores

• pHI: 0.313
• hipred: Y
• hipred_score: 0.626
• ghis: 0.412

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.169

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gucy2e
• Phenotype: homeostasis/metabolism 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); vision/eye phenotype

Zebrafish Information Network

• Gene name: gucy2d
• Affected structure: optomotor response
• Phenotype tag: abnormal
• Phenotype quality: arrested

Gene ontology

• Biological process: cGMP biosynthetic process;protein phosphorylation;signal transduction;receptor guanylyl cyclase signaling pathway;visual perception;regulation of rhodopsin mediated signaling pathway;intracellular signal transduction
• Cellular component: nuclear outer membrane;plasma membrane;integral component of plasma membrane;photoreceptor disc membrane
• Molecular function: peptide receptor activity;guanylate cyclase activity;protein kinase activity;protein binding;ATP binding;GTP binding;signaling receptor activity