PDE6B

phosphodiesterase 6B, the group of Phosphodiesterases

Basic information

Region (hg38): 4:625573-670782

Previous symbols: [ "PDEB" ]

Links

ENSG00000133256NCBI:5158OMIM:180072HGNC:8786Uniprot:P35913AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Night blindness, congenital stationary, autosomal dominant 2; Joubert syndrome 22; Retinitis pigmentosa 40AD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal; Neurologic; Ophthalmologic8394174; 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 (52 variants)
  • Retinitis pigmentosa (17 variants)
  • Retinitis pigmentosa 40 (16 variants)
  • Retinal dystrophy (12 variants)
  • Retinitis pigmentosa 40;Congenital stationary night blindness autosomal dominant 2 (2 variants)
  • Autosomal recessive retinitis pigmentosa (1 variants)
  • Congenital stationary night blindness autosomal dominant 2;Retinitis pigmentosa 40 (1 variants)
  • Tyrosinase-positive oculocutaneous albinism (1 variants)
  • PDE6B-related disorder (1 variants)
  • Congenital stationary night blindness autosomal dominant 2 (1 variants)
  • Cone-rod dystrophy (1 variants)
  • See cases (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
15
clinvar
169
clinvar
3
clinvar
187
missense
6
clinvar
17
clinvar
399
clinvar
7
clinvar
5
clinvar
434
nonsense
25
clinvar
5
clinvar
30
start loss
1
clinvar
1
frameshift
20
clinvar
11
clinvar
31
inframe indel
1
clinvar
16
clinvar
17
splice donor/acceptor (+/-2bp)
11
clinvar
20
clinvar
2
clinvar
33
splice region
1
24
35
2
62
non coding
1
clinvar
1
clinvar
24
clinvar
103
clinvar
42
clinvar
171
Total 64 54 457 279 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)438191
4-625629-G-T Uncertain significance (Oct 04, 2019)933238
4-625635-C-T Likely benign (Dec 30, 2021)2066809
4-625648-GC-G Pathogenic (Aug 10, 2023)1069615
4-625649-C-T Uncertain significance (Dec 14, 2023)1948441
4-625651-C-T Inborn genetic diseases Conflicting classifications of pathogenicity (Jan 04, 2024)968558
4-625652-G-A Benign (Jan 31, 2024)784032
4-625656-C-T Likely benign (Apr 20, 2023)2857881
4-625672-C-G Uncertain significance (Jan 15, 2022)1515857
4-625674-C-T PDE6B-related disorder Likely benign (Dec 11, 2023)1105288
4-625675-G-A Uncertain significance (Aug 09, 2022)1499587
4-625675-G-T Uncertain significance (Nov 13, 2023)1716213
4-625681-G-T Inborn genetic diseases Uncertain significance (Aug 16, 2022)960655
4-625684-C-T Uncertain significance (Sep 06, 2023)956267
4-625685-G-A Retinitis pigmentosa • Congenital stationary night blindness autosomal dominant 2 • Inborn genetic diseases Conflicting classifications of pathogenicity (Sep 26, 2023)903660
4-625697-G-C Uncertain significance (Jan 12, 2022)954082
4-625700-A-G Inborn genetic diseases Uncertain significance (Jun 27, 2023)2319089
4-625704-A-G Likely benign (Sep 02, 2020)1104529
4-625705-CTG-C Pathogenic (Jul 12, 2022)1371337
4-625712-C-G Uncertain significance (Aug 07, 2023)2995279
4-625713-T-G Likely benign (Jul 19, 2022)1560704
4-625719-T-A Uncertain significance (Nov 27, 2021)1386331
4-625721-T-A Uncertain significance (Dec 05, 2022)3004818
4-625726-G-A Uncertain significance (May 08, 2023)1983550
4-625726-G-C Uncertain significance (Sep 01, 2021)1397831

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PDE6Bprotein_codingprotein_codingENST00000496514 2245199
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
2.62e-270.00075111701119785401257480.0354
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.7985725211.100.00003575664
Missense in Polyphen222204.811.08392289
Synonymous-1.422572301.120.00001861562
Loss of Function0.5064346.70.9200.00000235524

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.03210.0321
Ashkenazi Jewish0.01020.00997
East Asian0.0008160.000761
Finnish0.04330.0430
European (Non-Finnish)0.05760.0567
Middle Eastern0.0008160.000761
South Asian0.009280.00922
Other0.04020.0395

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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