GeneBe

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 (Definitive), mode of inheritance: AR
  • 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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Choroidal dystrophy, central areolar 1; Cone-rod dystrophy 6; Leber congenital amaurosis, type 1; Cone-Rod dystrophy, autosomal recessive; Night blindness, congenital stationary, type 1IAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingOphthalmologic8554074; 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.

  • Leber_congenital_amaurosis_1 (1359 variants)
  • Cone-rod_dystrophy_6 (1282 variants)
  • not_provided (200 variants)
  • Inborn_genetic_diseases (129 variants)
  • Retinal_dystrophy (87 variants)
  • GUCY2D-related_recessive_retinopathy (59 variants)
  • Choroidal_dystrophy,_central_areolar,_1 (50 variants)
  • Night_blindness,_congenital_stationary,_type1i (45 variants)
  • not_specified (40 variants)
  • GUCY2D-related_disorder (34 variants)
  • Leber_congenital_amaurosis (24 variants)
  • Cone-rod_dystrophy (5 variants)
  • Cone_dystrophy (4 variants)
  • Retinal_disorders (3 variants)
  • Optic_atrophy (3 variants)
  • Retinitis_pigmentosa (2 variants)
  • Early-onset_retinal_dystrophy (2 variants)
  • Progressive_cone_dystrophy_(without_rod_involvement) (2 variants)
  • Autosomal_recessive_optic_atrophy (2 variants)
  • Abnormal_electroretinogram (2 variants)
  • Nystagmus (2 variants)
  • Autosomal_recessive_congenital_ichthyosis_3 (1 variants)
  • POLR-related_leukodystrophy (1 variants)
  • GUCY2D_retinopathy (1 variants)
  • Macular_dystrophy (1 variants)
  • Cataract (1 variants)
  • Visual_impairment (1 variants)
  • Congenital_blindness (1 variants)
  • maculopathy (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. These statistics are base on transcript: NM_000000180.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
14
clinvar
425
clinvar
7
clinvar
 446
missense
23
clinvar
66
clinvar
576
clinvar
26
clinvar
4
clinvar
 695
nonsense
39
clinvar
7
clinvar
2
clinvar
 48
start loss
5
1
 6
frameshift
61
clinvar
21
clinvar
6
clinvar
 88
splice donor/acceptor (+/-2bp)
20
clinvar
15
clinvar
4
clinvar
 39
Total 148 110 602 451 11

Highest pathogenic variant AF is 0.0002727853

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
GUCY2Dprotein_codingprotein_codingENST00000254854 1817746
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
6.46e-100.99812559101571257480.000624
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.7815986540.9140.00004496880
Missense in Polyphen217274.730.789862975
Synonymous-0.6163012881.050.00002052455
Loss of Function2.862242.00.5240.00000224455

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0006640.000661
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.003920.00380
European (Non-Finnish)0.0004480.000440
Middle Eastern0.00005440.0000544
South Asian0.0001320.000131
Other0.0006890.000652

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerHighMediumHigh

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