PDE6A

phosphodiesterase 6A, the group of Phosphodiesterases

Basic information

Region (hg38): 5:149857953-149944793

Previous symbols: [ "PDEA" ]

Links

ENSG00000132915 ∙ NCBI:5145 ∙ OMIM:180071 ∙ HGNC:8785 ∙ Uniprot:P16499 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 43 (Strong), mode of inheritance: AR
• retinitis pigmentosa 43 (Definitive), mode of inheritance: AR
• inherited retinal dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 43	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	Ophthalmologic	7493036; 18723146; 21039428

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE6A gene.

• not provided (42 variants)
• Retinitis pigmentosa 43 (12 variants)
• Retinitis pigmentosa (11 variants)
• Inborn genetic diseases (2 variants)
• Retinal dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE6A 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			5	119	10	134
missense	4	4	339	6	1	354
nonsense	21	5	2			28
start loss			1			1
frameshift	22	7	5			34
inframe indel			5	1		6
splice donor/acceptor (+/-2bp)	7	16	1			24
splice region			19	27	2	48
non coding			62	69	29	160
Total	54	32	420	195	40

Highest pathogenic variant AF is 0.0000657

Variants in PDE6A

This is a list of pathogenic ClinVar variants found in the PDE6A region.

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

Position	Type	Phenotype	Significance	ClinVar
5-149858006-G-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
5-149858042-G-C		Retinitis pigmentosa	Likely benign (Jan 12, 2018)
5-149858124-C-G		Retinitis pigmentosa	Benign (Jan 12, 2018)
5-149858126-T-G		Retinitis pigmentosa	Benign (Jan 12, 2018)
5-149858178-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
5-149858233-T-C		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
5-149858253-CCATAA-C		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
5-149858269-G-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
5-149858275-G-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
5-149858279-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
5-149858280-G-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
5-149858313-A-G		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
5-149858353-C-T		Retinitis pigmentosa	Benign (Jan 13, 2018)
5-149858370-T-G		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
5-149858434-G-A		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
5-149858495-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
5-149858512-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
5-149858559-G-A		Retinitis pigmentosa	Benign (Jan 13, 2018)
5-149858666-G-A		Retinitis pigmentosa	Likely benign (Jan 12, 2018)
5-149858701-C-T		Retinitis pigmentosa	Benign (Jan 13, 2018)
5-149858757-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
5-149858785-T-C		Retinitis pigmentosa	Benign (Jan 12, 2018)
5-149858791-AAG-A		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
5-149858814-ATC-A		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
5-149858815-TC-T		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE6A	protein_coding	protein_coding	ENST00000255266	22	86838

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.58e-25	0.00525	125614	0	134	125748	0.000533

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.426	504	478	1.05	0.0000283	5789
Missense in Polyphen		238	217.14	1.0961		2654
Synonymous	-0.104	183	181	1.01	0.0000116	1506
Loss of Function	0.873	41	47.5	0.863	0.00000240	560

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00103	0.00103
Ashkenazi Jewish	0.00	0.00
East Asian	0.00147	0.00147
Finnish	0.000142	0.000139
European (Non-Finnish)	0.000484	0.000484
Middle Eastern	0.00147	0.00147
South Asian	0.000687	0.000621
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This protein participates in processes of transmission and amplification of the visual signal.
• Disease: DISEASE: Retinitis pigmentosa 43 (RP43) [MIM:613810]: 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:10393062, ECO:0000269|PubMed:7493036}. 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 metabolism;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: 0.202

Intolerance Scores

• loftool: 0.543
• rvis_EVS: -0.19
• rvis_percentile_EVS: 39.31

Haploinsufficiency Scores

• pHI: 0.390
• hipred: N
• hipred_score: 0.322
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.476

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde6a
• 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); vision/eye phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;visual perception;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