PDE6B

phosphodiesterase 6B, the group of Phosphodiesterases

Basic information

Region (hg38): 4:625573-670782

Previous symbols: [ "PDEB" ]

Links

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

Phenotypes

GenCC

Source: genCC

• congenital stationary night blindness autosomal dominant 2 (Limited), mode of inheritance: AD
• inherited retinal dystrophy (Definitive), mode of inheritance: AR
• congenital stationary night blindness autosomal dominant 2 (Strong), mode of inheritance: AD
• retinitis pigmentosa 40 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• congenital stationary night blindness (Supportive), mode of inheritance: AD
• retinitis pigmentosa 40 (Definitive), 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 (1051 variants)
• Retinal_dystrophy (150 variants)
• Retinitis_pigmentosa (140 variants)
• Inborn_genetic_diseases (128 variants)
• Congenital_stationary_night_blindness_autosomal_dominant_2 (111 variants)
• Retinitis_pigmentosa_40 (97 variants)
• PDE6B-related_disorder (25 variants)
• not_specified (20 variants)
• Autosomal_recessive_retinitis_pigmentosa (6 variants)
• Congenital_Stationary_Night_Blindness,_Dominant (3 variants)
• Retinitis_Pigmentosa,_Recessive (2 variants)
• High_myopia (1 variants)
• Macular_dystrophy (1 variants)
• Leber_congenital_amaurosis (1 variants)
• Tyrosinase-positive_oculocutaneous_albinism (1 variants)
• Cone-rod_dystrophy (1 variants)
• Rod-cone_dystrophy (1 variants)
• See_cases (1 variants)
• Prostate_cancer (1 variants)
• Congenital_stationary_night_blindness (1 variants)
• Progressive_cone_dystrophy_(without_rod_involvement) (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. These statistics are base on transcript: NM_000000283.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			17	218	3	238
missense	11	42	486	44	6	589
nonsense	32	10	1			43
start loss		1	1			2
frameshift	34	18	1	1		54
splice donor/acceptor (+/-2bp)	17	24	4	1		46
Total	94	95	510	264	9

Highest pathogenic variant AF is 0.00018555962

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
		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

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

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