GUCY2D: Guanylate Cyclase 2D, Retinal
Key gene in retinal phototransduction and inherited retinal dystrophies
Gene Information Card
| Symbol | GUCY2D |
|---|---|
| Full Name | Guanylate Cyclase 2D, Retinal |
| Gene Type | protein-coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 3000 ncbi.nlm.nih.gov/gene/3000 |
| Ensembl ID | ENSG00000132518 |
| UniProt ID | Q02846 |
| OMIM ID | 600179 |
| HGNC ID | 4686 |
| Aliases | GUC1A4, GUC2D, LCA1, CORD6, RETGC-1, ROS-GC1 |
Description
GUCY2D encodes retinal guanylate cyclase 1 (RetGC-1), a membrane-bound guanylyl cyclase expressed predominantly in photoreceptor cells. It synthesizes cGMP from GTP, playing a critical role in the phototransduction cascade by regulating cGMP-gated cation channels. Mutations in GUCY2D are associated with Leber congenital amaurosis type 1 (LCA1) and cone-rod dystrophy type 6 (CORD6).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Leber congenital amaurosis 1 (LCA1) | Biallelic loss-of-function mutations reduce cGMP synthesis, impairing phototransduction and leading to severe early-onset retinal degeneration. | ClinVar, OMIM |
| Cone-rod dystrophy 6 (CORD6) | Dominant gain-of-function or dominant-negative mutations alter RetGC-1 activity, causing progressive cone and rod degeneration. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Retina | 27.8 | High |
| Brain (cerebellum) | 0.2 | Low |
| Testis | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 0.0 | Not expressed |
| Y79 (retinoblastoma) | 0.0 | Not expressed |
| HEK293 (embryonic kidney) | 0.0 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1483C>T (p.Arg495Trp) | Missense | Unknown | Dominant-negative; associated with CORD6 |
| c.1645C>T (p.Arg549Cys) | Missense | Unknown | Gain-of-function; associated with CORD6 |
| c.2179G>A (p.Glu727Lys) | Missense | Unknown | Loss-of-function; associated with LCA1 |
| c.2512C>T (p.Arg838Cys) | Missense | Unknown | Loss-of-function; associated with LCA1 |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., p.Glu727Lys, p.Arg838Cys) cause LCA1 by reducing or abolishing cGMP synthesis.
Gain of Function (GOF)
Dominant gain-of-function mutations (e.g., p.Arg549Cys) increase basal cGMP levels, leading to CORD6.
Dominant Negative (DN)
Dominant-negative mutations (e.g., p.Arg495Trp) interfere with wild-type RetGC-1 function, causing CORD6.
View complete mutation data：
Gene Ontology (GO)
| • guanylate cyclase activity (GO:0004383) | • protein binding (GO:0005515) |
| • plasma membrane (GO:0005886) | • detection of visible light (GO:0009584) |
| • visual perception (GO:0007601) | • integral component of membrane (GO:0016021) |
| • adenyl nucleotide binding (GO:0030554) | • intracellular signal transduction (GO:0035556) |
Pathways
• Phototransduction cascade (Reactome R-HSA-2514856)
• cGMP-PKG signaling pathway (KEGG hsa04022)
Protein Summary
Retinal guanylate cyclase 1 (RetGC-1) is a 1103-amino acid transmembrane protein with an extracellular N-terminal domain, a single transmembrane helix, and a cytoplasmic region containing a kinase homology domain and a guanylyl cyclase catalytic domain. It is activated by guanylyl cyclase-activating proteins (GCAPs) in response to low intracellular Ca2+ levels, restoring cGMP after light stimulation. Defects in RetGC-1 disrupt phototransduction recovery and cause retinal degeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GUCY2D Knockout HEK293 Cell Line | EDJ-KQ4823 | Human | 3000 | Details Get a Quote |
| GUCY2D Knockout HeLa Cell Line | EDJ-KQ53470 | Human | 3000 | Details Get a Quote |
| GUCY2D Knockout A-549 Cell Line | EDJ-KQ61942 | Human | 3000 | Details Get a Quote |
| GUCY2D Knockout HCT 116 Cell Line | EDJ-KQ70423 | Human | 3000 | Details Get a Quote |
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