PDE6H

phosphodiesterase 6H, the group of Phosphodiesterases

Basic information

Region (hg38): 12:14973042-14981865

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
retinal cone dystrophy 3A (Limited), mode of inheritance: AR
achromatopsia (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 (55 variants)
Retinal_cone_dystrophy_3A (7 variants)
Retinal_dystrophy (2 variants)
not_specified (2 variants)
PDE6H-related_disorder (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. These statistics are base on transcript: NM_000006205.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				12 clinvar		12
missense			28 clinvar	1 clinvar		29
nonsense	1 clinvar		1 clinvar			2
start loss			1			1
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	32	13	0

Highest pathogenic variant AF is 0.00006383013

Loading clinvar variants...

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
Phenotype

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
Cellular component
Molecular function: enzyme inhibitor activity;protein binding;cGMP binding;3',5'-cyclic-GMP phosphodiesterase activity