PDE6H
protein-codingphosphodiesterase 6H, the group of Phosphodiesterases
Gene summary
This gene encodes the inhibitory (or gamma) subunit of the cone-specific cGMP phosphodiesterase, which is a tetramer composed of two catalytic chains (alpha and beta), and two inhibitory chains (gamma). It is specifically expressed in the retina, and is involved in the transmission and amplification of the visual signal. Mutations in this gene are associated with retinal cone dystrophy type 3A (RCD3A). [provided by RefSeq, Mar 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012398
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0018852
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0012398
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0012398
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0018852
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0012398
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
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
Comments: Inheritance is unclear, and may involve recessive model or incomplete penetrance
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PDE6H variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006205.3. 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 | 15 | 15 | ||||
| missense | 30 | 1 | 31 | |||
| nonsense | 1 | 2 | 3 | |||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 1 | 1 | 34 | 16 | 0 | 52 |
Highest pathogenic variant AF is 0.00006383013
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006196.1 | 3 | MANE Select | |
| Ensembl | ENSP00000266395.2 | 3 | MANE Select | |
| Ensembl | ENSP00000615570.1 | 3 | Standard | |
| Ensembl | ENSP00000615570.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Purine metabolism - Homo sapiens (human)
- Phosphodiesterases in neuronal function
- Purine nucleotides nucleosides metabolism
- Visual signal transduction: Cones
Biological Process
- activation of MAPK activity
- visual perception
- negative regulation of catalytic activity
- positive regulation of epidermal growth factor receptor signaling pathway
- positive regulation of G protein-coupled receptor signaling pathway
Molecular Function
- enzyme inhibitor activity
- protein binding
- cGMP binding
- 3',5'-cyclic-GMP phosphodiesterase activity
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000266395
- Coding exons
- 3
- Length
- 8844
- Individuals with no LoFs
- 125687
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 25
- Defined
- 125712
- p
- 0.0000994
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.195 | 43 | 46.7 | 0.920 | 0.00000241 | 542 |
| Missense (PolyPhen) | 22 | 23.89 | 0.92087 | 273 | ||
| Synonymous | -0.732 | 19 | 15.3 | 1.24 | 7.28e-7 | 159 |
| Loss of Function | 0.208 | 3 | 3.42 | 0.878 | 1.44e-7 | 44 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.;
- Disease
- DISEASE: Cone dystrophy, retinal 3A (RCD3A) [MIM:610024]: A rare form of cone dystrophy associated with supernormal rod responses. The disorder is characterized by reduced visual acuity, photoaversion, night blindness, and abnormal color vision. At an early age, the retina shows subtle depigmentation at the macula and, later, more obvious areas of atrophy. {ECO:0000269|PubMed:15629837}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.129
Intolerance Scores
- LoFtool
- 0.539
- RVIS EVS
- 0.1
- RVIS percentile EVS
- 60.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.583
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |