Achromatopsia 6
disease diseaseOn this page
Also known as ACHM6RCD3Aretinal cone dystrophy 3Aretinal cone dystrophy type 3A
Summary
Achromatopsia 6 (MONDO:0012398) is a disease caused by PDE6H (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: PDE6H (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 18
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | achromatopsia 6 |
| Mondo ID | MONDO:0012398 |
| MeSH | C566483 |
| OMIM | 610024 |
| DOID | DOID:0081025 |
| GARD | 0010648 |
| Is cancer (heuristic) | no |
Also known as: ACHM6 · RCD3A · retinal cone dystrophy 3A · retinal cone dystrophy type 3A
Data availability: 18 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › perceptual disorders › vision disorder › color vision disorder › achromatopsia › achromatopsia 6
Related subtypes (5): achromatopsia 2, achromatopsia 3, blue cone monochromacy, achromatopsia 4, achromatopsia 7
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
18 retrieved; paginated sample, class counts are floors:
10 uncertain significance, 5 benign, 2 conflicting classifications of pathogenicity, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 37245 | NM_006205.3(PDE6H):c.35C>G (p.Ser12Ter) | PDE6H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 881091 | NM_006205.3(PDE6H):c.232G>T (p.Ala78Ser) | PDE6H | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1098417 | NM_006205.3(PDE6H):c.237G>C (p.Gln79His) | PDE6H | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 307783 | NM_006205.3(PDE6H):c.*47G>C | PDE6H | Uncertain significance | criteria provided, single submitter |
| 307784 | NM_006205.3(PDE6H):c.*71C>T | PDE6H | Uncertain significance | criteria provided, single submitter |
| 307785 | NM_006205.3(PDE6H):c.*77C>G | PDE6H | Uncertain significance | criteria provided, single submitter |
| 307786 | NM_006205.3(PDE6H):c.*134G>A | PDE6H | Uncertain significance | criteria provided, single submitter |
| 307789 | NM_006205.3(PDE6H):c.*358T>G | PDE6H | Uncertain significance | criteria provided, single submitter |
| 307790 | NM_006205.3(PDE6H):c.*369A>G | PDE6H | Uncertain significance | criteria provided, single submitter |
| 3780109 | NM_006205.3(PDE6H):c.135-2A>G | PDE6H | Uncertain significance | criteria provided, single submitter |
| 883445 | NM_006205.3(PDE6H):c.-42C>T | PDE6H | Uncertain significance | criteria provided, single submitter |
| 883446 | NM_006205.3(PDE6H):c.59G>A (p.Arg20His) | PDE6H | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 307780 | NM_006205.3(PDE6H):c.-59G>C | PDE6H | Benign | criteria provided, multiple submitters, no conflicts |
| 307781 | NM_006205.3(PDE6H):c.-29G>C | PDE6H | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
| 307782 | NM_006205.3(PDE6H):c.195A>G (p.Pro65=) | PDE6H | Benign | criteria provided, multiple submitters, no conflicts |
| 307787 | NM_006205.3(PDE6H):c.*301A>G | PDE6H | Benign | criteria provided, multiple submitters, no conflicts |
| 307788 | NM_006205.3(PDE6H):c.*319T>C | PDE6H | Benign | criteria provided, multiple submitters, no conflicts |
| 883444 | NM_006205.3(PDE6H):c.-73C>A | PDE6H | Benign | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| PDE6H | Strong | Autosomal recessive | achromatopsia 6 | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PDE6H | Orphanet:49382 | Achromatopsia |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| PDE6H | HGNC:8790 | ENSG00000139053 | Q13956 | Retinal cone rhodopsin-sensitive cGMP 3’,5’-cyclic phosphodiesterase subunit gamma | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PDE6H | Retinal cone rhodopsin-sensitive cGMP 3’,5’-cyclic phosphodiesterase subunit gamma | 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. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PDE6H | Other/Unknown | no | PDE6_gamma, PDE6_gamma_sf |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| monocyte | 1 |
| mononuclear cell | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PDE6H | 83 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, monocyte, mononuclear cell |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PDE6H | 875 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| PDE6H | Q13956 | 67.61 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| positive regulation of G protein-coupled receptor signaling pathway | 1 | 1053.2× | 0.004 | PDE6H |
| positive regulation of epidermal growth factor receptor signaling pathway | 1 | 495.6× | 0.004 | PDE6H |
| positive regulation of MAPK cascade | 1 | 80.6× | 0.013 | PDE6H |
| visual perception | 1 | 79.5× | 0.013 | PDE6H |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0
Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| PDE6H | VARDENAFIL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| PDE6H | 6 | 4 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| VARDENAFIL | 4 | PDE6H |
| SILDENAFIL | 4 | PDE6H |
| TADALAFIL | 4 | PDE6H |
| DIPYRIDAMOLE | 4 | PDE6H |
| ZAPRINAST | 2 | PDE6H |
| TBA-7371 | 2 | PDE6H |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PDE6H | 51 | Binding:49, ADMET:2 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
6 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| VARDENAFIL | 4 | PDE6H |
| SILDENAFIL | 4 | PDE6H |
| TADALAFIL | 4 | PDE6H |
| DIPYRIDAMOLE | 4 | PDE6H |
| ZAPRINAST | 2 | PDE6H |
| TBA-7371 | 2 | PDE6H |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | PDE6H |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 0 |
Undrugged target profiles
0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: PDE6H