Retinitis pigmentosa 43

Summary

Retinitis pigmentosa 43 (MONDO:0013437) is a disease caused by PDE6A (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PDE6A (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 86

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 43
Mondo ID	MONDO:0013437
OMIM	613810
DOID	DOID:0110379
UMLS	C3151139
MedGen	462489
GARD	0015716
Is cancer (heuristic)	no

Also known as: PDE6A retinitis pigmentosa · retinitis pigmentosa 43 · retinitis pigmentosa caused by mutation in PDE6A · retinitis pigmentosa type 43 · RP43

Data availability: 86 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › retinitis pigmentosa › retinitis pigmentosa 43

Related subtypes (101): retinitis pigmentosa 6, cone-rod dystrophy 2, retinitis pigmentosa 1, retinitis pigmentosa 9, retinitis pigmentosa 10, dominant pericentral pigmentary retinopathy, late-adult onset retinitis pigmentosa, autosomal recessive pericentral pigmentary retinopathy, retinitis pigmentosa 3, retinitis pigmentosa 24, retinitis pigmentosa 23, retinitis pigmentosa 34, retinitis pigmentosa 2, retinitis pigmentosa Y-linked, retinitis pigmentosa 13, retinitis pigmentosa 12, retinitis pigmentosa 14, retinitis pigmentosa 11, retinitis pigmentosa 17, retinitis pigmentosa 18, retinitis pigmentosa 19, retinitis pigmentosa 22, retinitis pigmentosa 25, retinitis pigmentosa 28, retinitis pigmentosa 30, retinitis pigmentosa 7, retinitis pigmentosa 26, retinitis pigmentosa 32, retinitis pigmentosa 31, retinitis pigmentosa 35, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 37, retinitis pigmentosa 41, retinitis pigmentosa 29, retinitis pigmentosa 46, retinitis pigmentosa 42, retinitis pigmentosa 50, retinitis pigmentosa 54, retinitis pigmentosa 51, retinitis pigmentosa 55, retinitis pigmentosa 56, retinitis pigmentosa 57, retinitis pigmentosa 58, cone-rod dystrophy 15, retinitis pigmentosa 4, retinitis pigmentosa 27, retinitis pigmentosa 49, retinitis pigmentosa 47, retinitis pigmentosa 45, retinitis pigmentosa 44, retinitis pigmentosa 20, retinitis pigmentosa 40, retinitis pigmentosa 39, retinitis pigmentosa 48, retinitis pigmentosa 59, retinitis pigmentosa 38, retinitis pigmentosa 60, retinitis pigmentosa 61, retinitis pigmentosa 62, retinitis pigmentosa 63, cone-rod dystrophy 16, retinitis pigmentosa 66, retinitis pigmentosa with or without situs inversus, retinitis pigmentosa 67, retinitis pigmentosa 68, retinitis pigmentosa 69, retinitis pigmentosa 70, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, retinitis pigmentosa 74, retinitis pigmentosa 75, retinitis pigmentosa 76, retinitis pigmentosa 77, retinitis pigmentosa 92, retinitis pigmentosa 93, retinitis pigmentosa 83, retinitis pigmentosa 84, retinitis pigmentosa 85, retinitis pigmentosa 86, retinitis pigmentosa 87 with choroidal involvement, retinitis pigmentosa 88, retinitis pigmentosa 90, retinitis pigmentosa 81, retinitis pigmentosa 78, retinitis pigmentosa 79, retinitis pigmentosa 80, retinitis pigmentosa 94, variable age at onset, retinitis pigmentosa 53, retinitis pigmentosa 65, retinitis pigmentosa 64, retinitis pigmentosa 95, retinitis pigmentosa 96, retinitis pigmentosa 97, retinitis pigmentosa 98, retinitis pigmentosa 99, retinitis pigmentosa 100, retinitis pigmentosa 101, retinitis pigmentosa 7, digenic

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

86 retrieved; paginated sample, class counts are floors:

20 pathogenic, 19 conflicting classifications of pathogenicity, 17 uncertain significance, 13 likely pathogenic, 12 pathogenic/likely pathogenic, 3 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065769	NM_000440.3(PDE6A):c.205C>T (p.Gln69Ter)	PDE6A	Pathogenic	criteria provided, single submitter
1213871	NM_000440.3(PDE6A):c.1117G>T (p.Glu373Ter)	PDE6A	Pathogenic	criteria provided, multiple submitters, no conflicts
1213872	NM_000440.3(PDE6A):c.1560dup (p.Cys521fs)	PDE6A	Pathogenic	criteria provided, single submitter
1213873	NM_000440.3(PDE6A):c.2317C>T (p.Gln773Ter)	PDE6A	Pathogenic	criteria provided, single submitter
1213874	NM_000440.3(PDE6A):c.2135+1G>T	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1297096	NM_000440.3(PDE6A):c.1684C>T (p.Arg562Trp)	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13110	NM_000440.3(PDE6A):c.1749C>G (p.Tyr583Ter)	PDE6A	Pathogenic	criteria provided, multiple submitters, no conflicts
13111	NM_000440.3(PDE6A):c.1032C>A (p.Ser344Arg)	PDE6A	Pathogenic	no assertion criteria provided
13112	NM_000440.3(PDE6A):c.1683G>A (p.Trp561Ter)	PDE6A	Pathogenic	criteria provided, single submitter
1419945	NM_000440.3(PDE6A):c.1286G>A (p.Trp429Ter)	PDE6A	Pathogenic	criteria provided, multiple submitters, no conflicts
1686015	NM_000440.3(PDE6A):c.1838+1G>A	PDE6A	Pathogenic	criteria provided, single submitter
194473	NM_000440.3(PDE6A):c.1926+1G>A	PDE6A	Pathogenic	criteria provided, multiple submitters, no conflicts
195462	NM_000440.3(PDE6A):c.2332_2335del (p.Asp778fs)	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225119	NM_000440.3(PDE6A):c.1408-2A>G	PDE6A	Pathogenic	criteria provided, single submitter
2445600	NM_000440.3(PDE6A):c.1054del (p.Gln352fs)	PDE6A	Pathogenic	no assertion criteria provided
29874	NM_000440.3(PDE6A):c.2053G>A (p.Val685Met)	PDE6A	Pathogenic	criteria provided, multiple submitters, no conflicts
3007518	NM_000440.3(PDE6A):c.715C>T (p.Gln239Ter)	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
425359	NM_000440.3(PDE6A):c.1955_1974dup (p.Ile659fs)	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4293098	NM_000440.3(PDE6A):c.2097del (p.Gln699fs)	PDE6A	Pathogenic	criteria provided, single submitter
437982	NM_000440.3(PDE6A):c.1630C>T (p.Arg544Trp)	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
437983	NM_000440.3(PDE6A):c.1957C>T (p.Arg653Ter)	PDE6A	Pathogenic	criteria provided, multiple submitters, no conflicts
437984	NM_000440.3(PDE6A):c.769C>T (p.Arg257Ter)	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
631962	NM_000440.3(PDE6A):c.2275-1G>A	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
636057	NM_000440.3(PDE6A):c.627+2T>G	PDE6A	Pathogenic	criteria provided, multiple submitters, no conflicts
812368	NM_000440.3(PDE6A):c.1960C>T (p.Gln654Ter)	PDE6A	Pathogenic	criteria provided, single submitter
847048	NM_000440.3(PDE6A):c.1724T>C (p.Leu575Pro)	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
855351	NM_000440.3(PDE6A):c.998+1G>A	PDE6A	Pathogenic	criteria provided, multiple submitters, no conflicts
865985	NM_000440.3(PDE6A):c.2302G>T (p.Glu768Ter)	PDE6A	Pathogenic	criteria provided, multiple submitters, no conflicts
866022	NM_000440.3(PDE6A):c.1407+1G>C	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866351	NM_000440.3(PDE6A):c.1620+2T>A	PDE6A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
PDE6A	Definitive	Autosomal recessive	retinitis pigmentosa 43	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDE6A	Orphanet:791	Retinitis pigmentosa

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
PDE6A	HGNC:8785	ENSG00000132915	P16499	Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDE6A	Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit alpha	Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3’,5’-cyclic GMP.

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)
PDE6A	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
cauda epididymis	1
corpus epididymis	1
endometrium epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDE6A	85	tissue_specific	marker	corpus epididymis, cauda epididymis, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDE6A	1,032

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PDE6A	P16499	89.80

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of the phototransduction cascade	1	951.7×	0.003	PDE6A
Inactivation, recovery and regulation of the phototransduction cascade	1	317.2×	0.005	PDE6A
Ca2+ pathway	1	178.4×	0.006	PDE6A

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
negative regulation of cAMP/PKA signal transduction	1	601.9×	0.007	PDE6A
retina development in camera-type eye	1	255.3×	0.008	PDE6A
visual perception	1	79.5×	0.017	PDE6A
signal transduction	1	16.1×	0.062	PDE6A

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
PDE6A	VARDENAFIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDE6A	8	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VARDENAFIL	4	PDE6A
SILDENAFIL	4	PDE6A
TADALAFIL	4	PDE6A
DIPYRIDAMOLE	4	PDE6A
ANTAZOLINE	4	PDE6A
ZAPRINAST	2	PDE6A
TBA-7371	2	PDE6A
JNJ-42396302	1	PDE6A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PDE6A	69	Binding:65, ADMET:3, Functional:1

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

8 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	PDE6A
SILDENAFIL	4	PDE6A
TADALAFIL	4	PDE6A
DIPYRIDAMOLE	4	PDE6A
ANTAZOLINE	4	PDE6A
ZAPRINAST	2	PDE6A
TBA-7371	2	PDE6A
JNJ-42396302	1	PDE6A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PDE6A
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.