PDE6H

phosphodiesterase 6H, the group of Phosphodiesterases

Basic information

Region (hg38): 12:14973041-14981865

Links

ENSG00000139053 ∙ NCBI:5149 ∙ OMIM:601190 ∙ HGNC:8790 ∙ Uniprot:Q13956 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinal cone dystrophy 3A (Strong), mode of inheritance: AR
• retinal cone dystrophy 3A (Strong), mode of inheritance: AR
• achromatopsia (Supportive), mode of inheritance: AR
• retinal cone dystrophy 3A (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Achromatopsia 6; Retinal cone dystrophy 3A	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	Ophthalmologic	15629837; 22901948
Inheritance is unclear, and may involve recessive model or incomplete penetrance

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE6H gene.

• not provided (50 variants)
• Retinal cone dystrophy 3A (17 variants)
• Inborn genetic diseases (2 variants)
• PDE6H-Related Disorders (1 variants)
• Achromatopsia 6 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE6H 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				9	1	10
missense			26			26
nonsense			1			1
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	4		6
non coding			7	5	4	16
Total	0	0	35	14	5

Variants in PDE6H

This is a list of pathogenic ClinVar variants found in the PDE6H region.

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

Position	Type	Phenotype	Significance	ClinVar
12-14973055-C-A		Retinal cone dystrophy 3A	Benign (Jan 13, 2018)
12-14973069-G-C		Retinal cone dystrophy 3A	Benign (Jan 13, 2018)
12-14973086-C-T		Retinal cone dystrophy 3A	Uncertain significance (Apr 27, 2017)
12-14977984-G-C		Retinal cone dystrophy 3A	Benign/Likely benign (Oct 01, 2022)
12-14978015-G-C			Uncertain significance (May 03, 2022)
12-14978021-C-G			Uncertain significance (Mar 22, 2022)
12-14978044-C-T			Uncertain significance (Sep 26, 2023)
12-14978047-C-G		Achromatopsia 6 • Retinal cone dystrophy 3A • PDE6H-related disorder	Conflicting classifications of pathogenicity (Jan 12, 2024)
12-14978055-G-T			Uncertain significance (Nov 28, 2022)
12-14978058-C-T			Uncertain significance (Oct 05, 2022)
12-14978065-C-T		not specified	Uncertain significance (Sep 26, 2022)
12-14978070-C-T			Uncertain significance (Jul 26, 2022)
12-14978071-G-A		Retinal cone dystrophy 3A	Uncertain significance (Jan 19, 2024)
12-14978071-G-T			Uncertain significance (Mar 20, 2021)
12-14978073-A-G			Uncertain significance (Oct 30, 2023)
12-14978084-C-G			Likely benign (Feb 08, 2023)
12-14978102-G-A			Likely benign (Jun 25, 2023)
12-14978107-G-A			Uncertain significance (Sep 12, 2022)
12-14978111-A-G			Likely benign (Nov 26, 2019)
12-14978124-C-A			Uncertain significance (Oct 24, 2022)
12-14978128-C-G			Uncertain significance (Mar 20, 2022)
12-14978129-A-G			Likely benign (Apr 20, 2023)
12-14978136-G-A			Uncertain significance (Aug 05, 2022)
12-14978137-G-A			Uncertain significance (Jan 13, 2021)
12-14978140-T-A			Uncertain significance (Sep 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE6H	protein_coding	protein_coding	ENST00000266395	3	8844

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00829	0.581	125687	0	25	125712	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.195	43	46.7	0.920	0.00000241	542
Missense in Polyphen		22	23.89	0.92087		273
Synonymous	-0.732	19	15.3	1.24	7.28e-7	159
Loss of Function	0.208	3	3.42	0.878	1.44e-7	44

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
• Disease: DISEASE: Cone dystrophy, retinal 3A (RCD3A) [MIM:610024]: A rare form of cone dystrophy associated with supernormal rod responses. The disorder is characterized by reduced visual acuity, photoaversion, night blindness, and abnormal color vision. At an early age, the retina shows subtle depigmentation at the macula and, later, more obvious areas of atrophy. {ECO:0000269|PubMed:15629837}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Purine metabolism - Homo sapiens (human);Phosphodiesterases in neuronal function;Purine nucleotides nucleosides metabolism;Visual signal transduction: Cones (Consensus)

Recessive Scores

• pRec: 0.129

Intolerance Scores

• loftool: 0.539
• rvis_EVS: 0.1
• rvis_percentile_EVS: 60.96

Haploinsufficiency Scores

• pHI: 0.327
• hipred: N
• hipred_score: 0.398
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.583

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde6h

Gene ontology

• Biological process: activation of MAPK activity;visual perception;negative regulation of catalytic activity;positive regulation of epidermal growth factor receptor signaling pathway;positive regulation of G protein-coupled receptor signaling pathway;response to stimulus
• Molecular function: enzyme inhibitor activity;protein binding;cGMP binding;3',5'-cyclic-GMP phosphodiesterase activity