Retinitis pigmentosa 40

disease

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Also known as PDE6B retinitis pigmentosaretinitis pigmentosa caused by mutation in PDE6Bretinitis pigmentosa type 40retinitis pigmentosa-40RP40

Summary

Retinitis pigmentosa 40 (MONDO:0013429) is a disease caused by PDE6B (GenCC Definitive), with 4 cohort genes.

At a glance

Causal gene: PDE6B (GenCC Definitive)
Cohort genes: 4
ClinVar variants: 102

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 40
Mondo ID	MONDO:0013429
OMIM	613801
DOID	DOID:0110375
UMLS	C3151107
MedGen	462457
GARD	0015709
Is cancer (heuristic)	no

Also known as: PDE6B retinitis pigmentosa · retinitis pigmentosa 40 · retinitis pigmentosa caused by mutation in PDE6B · retinitis pigmentosa type 40 · retinitis pigmentosa-40 · RP40

Data availability: 102 ClinVar variants · 4 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 40

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

102 retrieved; paginated sample, class counts are floors:

31 pathogenic, 22 uncertain significance, 19 likely pathogenic, 14 pathogenic/likely pathogenic, 12 conflicting classifications of pathogenicity, 2 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1713277	NC_000004.12:g.670405_677862del	ATP5ME	Pathogenic	no assertion criteria provided
1070411	NM_000283.4(PDE6B):c.1798G>A (p.Asp600Asn)	PDE6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184486	NM_000283.4(PDE6B):c.853-1G>A	PDE6B	Pathogenic	no assertion criteria provided
1184487	NM_000283.4(PDE6B):c.1160C>T (p.Pro387Leu)	PDE6B	Pathogenic	criteria provided, single submitter
1184488	NM_000283.4(PDE6B):c.1927_1967del (p.Asn643fs)	PDE6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1213876	NM_000283.4(PDE6B):c.510C>G (p.Tyr170Ter)	PDE6B	Pathogenic	criteria provided, single submitter
13103	NM_000283.4(PDE6B):c.892C>T (p.Gln298Ter)	PDE6B	Pathogenic	criteria provided, multiple submitters, no conflicts
13104	NM_000283.4(PDE6B):c.1591C>T (p.Arg531Ter)	PDE6B	Pathogenic	criteria provided, multiple submitters, no conflicts
13105	NM_000283.4(PDE6B):c.1488del (p.Thr497fs)	PDE6B	Pathogenic	criteria provided, multiple submitters, no conflicts
13106	NM_000283.4(PDE6B):c.1669C>T (p.His557Tyr)	PDE6B	Pathogenic	criteria provided, multiple submitters, no conflicts
13108	NM_000283.4(PDE6B):c.169_239dup (p.Leu83fs)	PDE6B	Pathogenic	criteria provided, single submitter
13109	NM_000283.4(PDE6B):c.2419T>A (p.Trp807Arg)	PDE6B	Pathogenic	no assertion criteria provided
1358080	NM_000283.4(PDE6B):c.262C>T (p.Gln88Ter)	PDE6B	Pathogenic	criteria provided, multiple submitters, no conflicts
143067	NM_000283.4(PDE6B):c.1604T>A (p.Ile535Asn)	PDE6B	Pathogenic	criteria provided, multiple submitters, no conflicts
1458483	NM_000283.4(PDE6B):c.1133G>A (p.Trp378Ter)	PDE6B	Pathogenic	criteria provided, multiple submitters, no conflicts
1475513	NM_000283.4(PDE6B):c.2197G>C (p.Ala733Pro)	PDE6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
167440	NM_000283.4(PDE6B):c.2193+1G>A	PDE6B	Pathogenic	criteria provided, multiple submitters, no conflicts
217798	NM_000283.4(PDE6B):c.1678C>T (p.Arg560Cys)	PDE6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
224742	NM_000283.4(PDE6B):c.1923_1969delinsTCTGGG (p.Asn643fs)	PDE6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
349392	NM_000283.4(PDE6B):c.2326G>A (p.Asp776Asn)	PDE6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3775278	NM_000283.4(PDE6B):c.869G>A (p.Trp290Ter)	PDE6B	Pathogenic	criteria provided, single submitter
4057199	NM_000283.4(PDE6B):c.669T>A (p.Tyr223Ter)	PDE6B	Pathogenic	criteria provided, single submitter
4081880	NM_000283.4(PDE6B):c.2061dup (p.Asn688fs)	PDE6B	Pathogenic	no assertion criteria provided
419959	NM_000283.4(PDE6B):c.1860del (p.His620fs)	PDE6B	Pathogenic	criteria provided, multiple submitters, no conflicts
425324	NM_000283.4(PDE6B):c.886G>T (p.Glu296Ter)	PDE6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438188	NM_000283.4(PDE6B):c.1107+3A>G	PDE6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4537475	NM_000283.4(PDE6B):c.2463_2470del (p.Glu822fs)	PDE6B	Pathogenic	criteria provided, single submitter
522405	NM_000283.4(PDE6B):c.1832+1G>T	PDE6B	Pathogenic	criteria provided, multiple submitters, no conflicts
560477	NM_000283.4(PDE6B):c.1041_1042dup (p.Val348fs)	PDE6B	Pathogenic	no assertion criteria provided
560478	NM_000283.4(PDE6B):c.1107+2dup	PDE6B	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · 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
PDE6B	Definitive	Autosomal recessive	retinitis pigmentosa 40	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDE6B	Orphanet:714096	Congenital stationary night blindness, Riggs type
PDE6B	Orphanet:791	Retinitis pigmentosa
AGTR1	Orphanet:97369	Renal tubular dysgenesis of genetic origin

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PDE6B	HGNC:8786	ENSG00000133256	P35913	Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit beta	gencc,clinvar
AGTR1	HGNC:336	ENSG00000144891	P30556	Type-1 angiotensin II receptor	clinvar
PDE6B-AS1	HGNC:40438	ENSG00000242686		PDE6B antisense RNA 1	clinvar
ATP5ME	HGNC:846	ENSG00000169020	P56385	ATP synthase F(0) complex subunit e, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDE6B	Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit beta	Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3’,5’-cyclic GMP.
AGTR1	Type-1 angiotensin II receptor	Receptor for angiotensin II, a vasoconstricting peptide, which acts as a key regulator of blood pressure and sodium retention by the kidney.
ATP5ME	ATP synthase F(0) complex subunit e, mitochondrial	Subunit e, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of th…

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

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
GPCR	1	6.0×	0.471
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	InterPro (top 3)
PDE6B	Transcription factor	no	PDEase_catalytic_dom, GAF, HD/PDEase_dom
AGTR1	GPCR	yes	ATII_AT1_rcpt, ATII_rcpt, GPCR_Rhodpsn
PDE6B-AS1	Other/Unknown	no
ATP5ME	Other/Unknown	no	ATP_synth_F0_esu_mt

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
C1 segment of cervical spinal cord	1
right uterine tube	1
spinal cord	1
placenta	1
skin of hip	1
subcutaneous adipose tissue	1
cortical plate	1
male germ line stem cell (sensu Vertebrata) in testis	1
right frontal lobe	1
apex of heart	1
cardiac ventricle	1
heart left ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDE6B	183	broad	marker	C1 segment of cervical spinal cord, right uterine tube, spinal cord
AGTR1	224		marker	skin of hip, placenta, subcutaneous adipose tissue
PDE6B-AS1	146	tissue_specific	yes	right frontal lobe, cortical plate, male germ line stem cell (sensu Vertebrata) in testis
ATP5ME	295	ubiquitous	marker	apex of heart, cardiac ventricle, heart left ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AGTR1	2,651
ATP5ME	1,979
PDE6B	1,375
PDE6B-AS1	0

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AGTR1	P30556	11
ATP5ME	P56385	10

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PDE6B	P35913	89.72

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 4 evidence-associated genes (3 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 3 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	317.2×	0.047	PDE6B
Formation of ATP by chemiosmotic coupling	1	190.3×	0.047	ATP5ME
Cristae formation	1	115.3×	0.047	ATP5ME
Inactivation, recovery and regulation of the phototransduction cascade	1	105.7×	0.047	PDE6B
Ca2+ pathway	1	59.5×	0.059	PDE6B
Mitochondrial biogenesis	1	56.0×	0.059	ATP5ME
Cargo recognition for clathrin-mediated endocytosis	1	34.9×	0.071	AGTR1
Aerobic respiration and respiratory electron transport	1	29.5×	0.071	ATP5ME
Clathrin-mediated endocytosis	1	28.4×	0.071	AGTR1
Class A/1 (Rhodopsin-like receptors)	1	24.7×	0.071	AGTR1
Peptide ligand-binding receptors	1	24.7×	0.071	AGTR1
Organelle biogenesis and maintenance	1	22.0×	0.071	ATP5ME
GPCR ligand binding	1	21.4×	0.071	AGTR1
G alpha (q) signalling events	1	19.1×	0.073	AGTR1
GPCR downstream signalling	1	14.5×	0.090	AGTR1
Signaling by GPCR	1	13.4×	0.091	AGTR1
Membrane Trafficking	1	12.4×	0.093	AGTR1
Vesicle-mediated transport	1	11.6×	0.093	AGTR1
Metabolism	1	3.9×	0.249	ATP5ME
Signal Transduction	1	3.4×	0.267	AGTR1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
retinal cell apoptotic process	1	2808.7×	0.005	PDE6B
renin-angiotensin regulation of aldosterone production	1	1872.4×	0.005	AGTR1
maintenance of blood vessel diameter homeostasis by renin-angiotensin	1	1872.4×	0.005	AGTR1
phospholipase C-activating angiotensin-activated signaling pathway	1	1872.4×	0.005	AGTR1
regulation of renal sodium excretion	1	1404.3×	0.005	AGTR1
regulation of systemic arterial blood pressure by renin-angiotensin	1	1123.5×	0.005	AGTR1
positive regulation of cholesterol metabolic process	1	702.2×	0.007	AGTR1
positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	1	561.7×	0.007	AGTR1
angiotensin-activated signaling pathway	1	510.7×	0.007	AGTR1
phototransduction, visible light	1	432.1×	0.008	PDE6B
low-density lipoprotein particle remodeling	1	351.1×	0.009	AGTR1
positive regulation of macrophage derived foam cell differentiation	1	280.9×	0.009	AGTR1
proton motive force-driven ATP synthesis	1	267.5×	0.009	ATP5ME
regulation of vasoconstriction	1	267.5×	0.009	AGTR1
entrainment of circadian clock by photoperiod	1	244.2×	0.009	PDE6B
blood vessel diameter maintenance	1	208.1×	0.010	AGTR1
negative regulation of cAMP/PKA signal transduction	1	200.6×	0.010	PDE6B
positive regulation of reactive oxygen species metabolic process	1	170.2×	0.011	AGTR1
symbiont entry into host cell	1	133.8×	0.013	AGTR1
proton motive force-driven mitochondrial ATP synthesis	1	87.8×	0.019	ATP5ME
retina development in camera-type eye	1	85.1×	0.019	PDE6B
Rho protein signal transduction	1	82.6×	0.019	AGTR1
regulation of cell growth	1	73.9×	0.020	AGTR1
cell chemotaxis	1	61.7×	0.022	AGTR1
calcium-mediated signaling	1	61.1×	0.022	AGTR1
regulation of inflammatory response	1	56.2×	0.023	AGTR1
positive regulation of inflammatory response	1	48.4×	0.026	AGTR1
kidney development	1	46.8×	0.026	AGTR1
phospholipase C-activating G protein-coupled receptor signaling pathway	1	43.9×	0.027	AGTR1
positive regulation of cytosolic calcium ion concentration	1	39.0×	0.028	AGTR1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 3 of 4 evidence-associated genes (75%) 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
PDE6B	VARDENAFIL
AGTR1	IRBESARTAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AGTR1	88	4
PDE6B	6	4
PDE6B-AS1	0	0
ATP5ME	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VARDENAFIL	4	PDE6B
SILDENAFIL	4	PDE6B
TADALAFIL	4	PDE6B
DIPYRIDAMOLE	4	PDE6B
IRBESARTAN	4	AGTR1
LOSARTAN	4	AGTR1
SARALASIN	4	AGTR1
LOSARTAN POTASSIUM	4	AGTR1
CANDESARTAN CILEXETIL	4	AGTR1
TELMISARTAN	4	AGTR1
CLOTRIMAZOLE	4	AGTR1
SIMVASTATIN	4	AGTR1
VALSARTAN	4	AGTR1
RIMONABANT	4	AGTR1
ARIPIPRAZOLE	4	AGTR1
PONATINIB	4	AGTR1
OXYMETHOLONE	4	AGTR1
OLMESARTAN MEDOXOMIL	4	AGTR1
NORGESTIMATE	4	AGTR1
ROCURONIUM	4	AGTR1
PYRVINIUM	4	AGTR1
INDOCYANINE GREEN ACID FORM	4	AGTR1
BALSALAZIDE	4	AGTR1
ROSIGLITAZONE	4	AGTR1
SULCONAZOLE	4	AGTR1
MILTEFOSINE	4	AGTR1
BUTOCONAZOLE	4	AGTR1
SORAFENIB	4	AGTR1
NITAZOXANIDE	4	AGTR1
PIMOZIDE	4	AGTR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
AGTR1	421	Binding:315, Functional:105, ADMET:1
PDE6B	57	Binding:54, ADMET:3
ATP5ME	1	Binding:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
AGTR1	421

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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	PDE6B
SILDENAFIL	4	PDE6B
TADALAFIL	4	PDE6B
DIPYRIDAMOLE	4	PDE6B
IRBESARTAN	4	AGTR1
LOSARTAN	4	AGTR1
SARALASIN	4	AGTR1
LOSARTAN POTASSIUM	4	AGTR1
CANDESARTAN CILEXETIL	4	AGTR1
TELMISARTAN	4	AGTR1
CLOTRIMAZOLE	4	AGTR1
SIMVASTATIN	4	AGTR1
VALSARTAN	4	AGTR1
RIMONABANT	4	AGTR1
ARIPIPRAZOLE	4	AGTR1
PONATINIB	4	AGTR1
OXYMETHOLONE	4	AGTR1
OLMESARTAN MEDOXOMIL	4	AGTR1
NORGESTIMATE	4	AGTR1
ROCURONIUM	4	AGTR1
PYRVINIUM	4	AGTR1
INDOCYANINE GREEN ACID FORM	4	AGTR1
BALSALAZIDE	4	AGTR1
ROSIGLITAZONE	4	AGTR1
SULCONAZOLE	4	AGTR1
MILTEFOSINE	4	AGTR1
BUTOCONAZOLE	4	AGTR1
SORAFENIB	4	AGTR1
NITAZOXANIDE	4	AGTR1
PIMOZIDE	4	AGTR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	PDE6B, AGTR1
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	2	PDE6B-AS1, ATP5ME

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PDE6B-AS1	0	—
ATP5ME	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: PDE6B, AGTR1, PDE6B-AS1, ATP5ME