PDE6B

phosphodiesterase 6B, the group of Phosphodiesterases

Basic information

Region (hg38): 4:625572-670782

Previous symbols: [ "PDEB" ]

Links

ENSG00000133256 ∙ NCBI:5158 ∙ OMIM:180072 ∙ HGNC:8786 ∙ Uniprot:P35913 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 40 (Definitive), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• congenital stationary night blindness (Supportive), mode of inheritance: AD
• congenital stationary night blindness autosomal dominant 2 (Strong), mode of inheritance: AD
• retinitis pigmentosa 40 (Strong), mode of inheritance: AR
• congenital stationary night blindness autosomal dominant 2 (Strong), mode of inheritance: AD
• retinitis pigmentosa 40 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Night blindness, congenital stationary, autosomal dominant 2; Joubert syndrome 22; Retinitis pigmentosa 40	AD/AR	General	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	Musculoskeletal; Neurologic; Ophthalmologic	8394174; 8075643; 7599633; 17044014; 18854872; 20655036; 24166846; 30423442

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE6B gene.

• not provided (888 variants)
• Retinitis pigmentosa (156 variants)
• Congenital stationary night blindness autosomal dominant 2 (122 variants)
• Retinitis pigmentosa 40 (51 variants)
• Retinal dystrophy (41 variants)
• Inborn genetic diseases (39 variants)
• not specified (25 variants)
• Congenital stationary night blindness autosomal dominant 2;Retinitis pigmentosa 40 (4 variants)
• Retinitis pigmentosa 40;Congenital stationary night blindness autosomal dominant 2 (3 variants)
• Congenital Stationary Night Blindness, Dominant (3 variants)
• Retinitis Pigmentosa, Recessive (3 variants)
• Autosomal recessive retinitis pigmentosa (3 variants)
• Rod-cone dystrophy (2 variants)
• PDE6B-related condition (2 variants)
• PDE6B-related disease (1 variants)
• Autosomal recessive retinitis pigmentosa;Congenital Stationary Night Blindness, Dominant (1 variants)
• Progressive cone dystrophy (without rod involvement) (1 variants)
• Leber congenital amaurosis (1 variants)
• High myopia (1 variants)
• PDE6B-related disorder (1 variants)
• PDE6B-Related Disorders (1 variants)
• Congenital stationary night blindness (1 variants)
• Macular dystrophy (1 variants)
• Tyrosinase-positive oculocutaneous albinism (1 variants)
• Cone-rod dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE6B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	153	4	167
missense	5	16	362	6	5	394
nonsense	23	5				28
start loss			1			1
frameshift	15	9				24
inframe indel	1		16			17
splice donor/acceptor (+/-2bp)	10	17	2			29
splice region		1	21	31	2	55
non coding	1	1	23	93	41	159
Total	55	48	414	252	50

Highest pathogenic variant AF is 0.000184

Variants in PDE6B

This is a list of pathogenic ClinVar variants found in the PDE6B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-625627-A-G		Retinitis pigmentosa	Likely pathogenic (Jan 01, 2015)
4-625629-G-T			Uncertain significance (Oct 04, 2019)
4-625635-C-T			Likely benign (Dec 30, 2021)
4-625648-GC-G			Pathogenic (Aug 10, 2023)
4-625649-C-T			Uncertain significance (Dec 14, 2023)
4-625651-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 04, 2024)
4-625652-G-A			Benign (Jan 31, 2024)
4-625656-C-T			Likely benign (Apr 20, 2023)
4-625672-C-G			Uncertain significance (Jan 15, 2022)
4-625674-C-T		PDE6B-related disorder	Likely benign (Dec 11, 2023)
4-625675-G-A			Uncertain significance (Aug 09, 2022)
4-625675-G-T			Uncertain significance (Nov 13, 2023)
4-625681-G-T		Inborn genetic diseases	Uncertain significance (Aug 16, 2022)
4-625684-C-T			Uncertain significance (Sep 06, 2023)
4-625685-G-A		Congenital stationary night blindness autosomal dominant 2 • Retinitis pigmentosa • Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 26, 2023)
4-625697-G-C			Uncertain significance (Jan 12, 2022)
4-625700-A-G		Inborn genetic diseases	Uncertain significance (Jun 27, 2023)
4-625704-A-G			Likely benign (Sep 02, 2020)
4-625705-CTG-C			Pathogenic (Jul 12, 2022)
4-625712-C-G			Uncertain significance (Aug 07, 2023)
4-625713-T-G			Likely benign (Jul 19, 2022)
4-625719-T-A			Uncertain significance (Nov 27, 2021)
4-625721-T-A			Uncertain significance (Dec 05, 2022)
4-625726-G-A			Uncertain significance (May 08, 2023)
4-625726-G-C			Uncertain significance (Sep 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE6B	protein_coding	protein_coding	ENST00000496514	22	45199

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.62e-27	0.000751	117011	197	8540	125748	0.0354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.798	572	521	1.10	0.0000357	5664
Missense in Polyphen		222	204.81	1.0839		2289
Synonymous	-1.42	257	230	1.12	0.0000186	1562
Loss of Function	0.506	43	46.7	0.920	0.00000235	524

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0321	0.0321
Ashkenazi Jewish	0.0102	0.00997
East Asian	0.000816	0.000761
Finnish	0.0433	0.0430
European (Non-Finnish)	0.0576	0.0567
Middle Eastern	0.000816	0.000761
South Asian	0.00928	0.00922
Other	0.0402	0.0395

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This protein participates in processes of transmission and amplification of the visual signal. Necessary for the formation of a functional phosphodiesterase holoenzyme.
• Disease: DISEASE: Retinitis pigmentosa 40 (RP40) [MIM:613801]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:8394174, ECO:0000269|PubMed:8557257, ECO:0000269|PubMed:8595886, ECO:0000269|PubMed:8698075, ECO:0000269|PubMed:8956055, ECO:0000269|PubMed:9543643}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Night blindness, congenital stationary, autosomal dominant 2 (CSNBAD2) [MIM:163500]: A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. {ECO:0000269|PubMed:8075643}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Purine metabolism - Homo sapiens (human);Phototransduction - Homo sapiens (human);Phosphodiesterases in neuronal function;Signaling by GPCR;Signaling by WNT;Signal Transduction;visual signal transduction;Purine nucleotides nucleosides metabolism;Ca2+ pathway;Beta-catenin independent WNT signaling;Visual signal transduction: Rods;G alpha (i) signalling events;Activation of the phototransduction cascade;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.556

Intolerance Scores

• loftool: 0.868
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.05

Haploinsufficiency Scores

• pHI: 0.612
• hipred: N
• hipred_score: 0.337
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.157

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pde6b
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;visual perception;phototransduction, visible light;rhodopsin mediated signaling pathway;regulation of rhodopsin mediated signaling pathway;regulation of cytosolic calcium ion concentration;retina development in camera-type eye
• Cellular component: plasma membrane;photoreceptor disc membrane
• Molecular function: metal ion binding;3',5'-cyclic-GMP phosphodiesterase activity