Achromatopsia 5

Summary

Achromatopsia 5 (MONDO:0800196) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	achromatopsia 5
Mondo ID	MONDO:0800196
UMLS	C2751309
MedGen	416519
GARD	0026475
Is cancer (heuristic)	no

Also known as: ACHM5

Data availability: 14 ClinVar variants · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › hereditary macular dystrophy › cone dystrophy › cone dystrophy 4 › achromatopsia 5

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

14 retrieved; paginated sample, class counts are floors:

11 pathogenic, 2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
8763	NM_006204.4(PDE6C):c.85C>T (p.Arg29Trp)	PDE6C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8764	NM_006204.4(PDE6C):c.967T>A (p.Tyr323Asn)	PDE6C	Pathogenic	no assertion criteria provided
8765	NM_006204.4(PDE6C):c.256_257dup (p.Leu87fs)	PDE6C	Pathogenic	criteria provided, single submitter
8766	NM_006204.4(PDE6C):c.2367+1_2367+5del	PDE6C	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8767	NM_006204.4(PDE6C):c.1363A>G (p.Met455Val)	PDE6C	Pathogenic	no assertion criteria provided
8768	NM_006204.4(PDE6C):c.633G>C (p.Glu211Asp)	PDE6C	Pathogenic	no assertion criteria provided
8769	NM_006204.4(PDE6C):c.2368G>A (p.Glu790Lys)	PDE6C	Pathogenic	no assertion criteria provided
8770	NM_006204.4(PDE6C):c.481-12T>A	PDE6C	Pathogenic	no assertion criteria provided
8771	NM_006204.4(PDE6C):c.1483-2A>G	PDE6C	Pathogenic	no assertion criteria provided
8772	NM_006204.4(PDE6C):c.1805A>T (p.His602Leu)	PDE6C	Pathogenic	no assertion criteria provided
8773	NM_006204.4(PDE6C):c.826C>T (p.Arg276Ter)	PDE6C	Pathogenic	no assertion criteria provided
8774	NM_006204.4(PDE6C):c.2457T>A (p.Tyr819Ter)	PDE6C	Pathogenic	no assertion criteria provided
8775	NM_006204.4(PDE6C):c.1682dup (p.Tyr561Ter)	PDE6C	Pathogenic	no assertion criteria provided
487697	NM_006204.4(PDE6C):c.836T>C (p.Ile279Thr)	PDE6C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDE6C	Orphanet:1871	Progressive cone dystrophy
PDE6C	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
PDE6C	HGNC:8787	ENSG00000095464	P51160	Cone cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha'	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDE6C	Cone cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha'	As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PDE6C	Transcription factor	no		PDEase_catalytic_dom, GAF, HD/PDEase_dom

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
cerebellar hemisphere	1
male germ line stem cell (sensu Vertebrata) in testis	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDE6C	159	tissue_specific	marker	secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDE6C	903

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDE6C	P51160	7

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
retinal cone cell development	1	1404.3×	0.002	PDE6C
phototransduction, visible light	1	1296.3×	0.002	PDE6C
negative regulation of cAMP/PKA signal transduction	1	601.9×	0.002	PDE6C
visual perception	1	79.5×	0.013	PDE6C

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
PDE6C	VARDENAFIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDE6C	6	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VARDENAFIL	4	PDE6C
SILDENAFIL	4	PDE6C
TADALAFIL	4	PDE6C
DIPYRIDAMOLE	4	PDE6C
ZAPRINAST	2	PDE6C
TBA-7371	2	PDE6C

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PDE6C	103	Binding:97, ADMET:6

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PDE6C	103

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	PDE6C
SILDENAFIL	4	PDE6C
TADALAFIL	4	PDE6C
DIPYRIDAMOLE	4	PDE6C
ZAPRINAST	2	PDE6C
TBA-7371	2	PDE6C

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PDE6C
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.