PDE6C

phosphodiesterase 6C, the group of Phosphodiesterases

Basic information

Region (hg38): 10:93612537-93666010

Links

ENSG00000095464 ∙ NCBI:5146 ∙ OMIM:600827 ∙ HGNC:8787 ∙ Uniprot:P51160 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cone dystrophy 4 (Strong), mode of inheritance: AR
• cone dystrophy (Supportive), mode of inheritance: AD
• achromatopsia (Supportive), mode of inheritance: AR
• cone dystrophy 4 (Strong), mode of inheritance: AR
• cone dystrophy 4 (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
Cone dystrophy 4	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	19887631; 19615668

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE6C gene.

• not provided (30 variants)
• Achromatopsia (7 variants)
• Cone dystrophy 4 (3 variants)
• Isolated macular dystrophy (1 variants)
• Achromatopsia 5 (1 variants)
• PDE6C-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE6C 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	114	4	123
missense	6	6	243	5	2	262
nonsense	8	4				12
start loss						0
frameshift	18	4				22
inframe indel			5			5
splice donor/acceptor (+/-2bp)	5	12		1		18
splice region		1	17	24	2	44
non coding			12	72	10	94
Total	37	26	265	192	16

Highest pathogenic variant AF is 0.0000789

Variants in PDE6C

This is a list of pathogenic ClinVar variants found in the PDE6C region.

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

Position	Type	Phenotype	Significance	ClinVar
10-93612705-C-T		Achromatopsia • Cone dystrophy 4	Uncertain significance (Jan 13, 2018)
10-93612719-C-A		Achromatopsia • Cone dystrophy 4	Uncertain significance (Jan 12, 2018)
10-93612745-T-C		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
10-93612749-C-G			Likely benign (Nov 17, 2022)
10-93612749-C-T			Likely benign (Jan 17, 2024)
10-93612750-G-A			Uncertain significance (Oct 04, 2022)
10-93612758-A-T			Uncertain significance (Nov 27, 2023)
10-93612761-C-A			Pathogenic (Jul 14, 2023)
10-93612761-C-T			Likely benign (Apr 21, 2021)
10-93612770-GA-AC			Uncertain significance (Nov 28, 2023)
10-93612771-A-C		Inborn genetic diseases	Uncertain significance (Mar 29, 2023)
10-93612773-C-A			Uncertain significance (May 08, 2022)
10-93612782-T-G			Uncertain significance (Aug 05, 2022)
10-93612801-AG-A		Achromatopsia	Pathogenic (Dec 01, 2017)
10-93612802-G-C			Uncertain significance (Aug 23, 2021)
10-93612810-C-A			Likely benign (Nov 01, 2022)
10-93612810-C-T		Cone dystrophy 4 • Achromatopsia 5	Pathogenic/Likely pathogenic (Dec 19, 2024)
10-93612811-G-A			Uncertain significance (Jan 04, 2024)
10-93612813-G-A			Uncertain significance (May 04, 2022)
10-93612818-G-T			Uncertain significance (Jul 05, 2022)
10-93612826-G-A		Achromatopsia • Cone dystrophy 4	Uncertain significance (Mar 26, 2022)
10-93612830-A-T			Uncertain significance (Mar 02, 2022)
10-93612833-C-A			Likely benign (Oct 01, 2022)
10-93612849-G-A		Cone dystrophy 4 • Achromatopsia • Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
10-93612855-G-T		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE6C	protein_coding	protein_coding	ENST00000371447	22	53423

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.32e-16	0.942	125669	0	79	125748	0.000314

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	387	455	0.850	0.0000242	5716
Missense in Polyphen		142	196.23	0.72365		2518
Synonymous	-1.31	190	168	1.13	0.00000966	1535
Loss of Function	2.33	33	51.0	0.647	0.00000277	601

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00113	0.00113
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000272	0.000272
South Asian	0.000494	0.000490
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP. {ECO:0000269|PubMed:21127010, ECO:0000269|PubMed:28583373}.
• Disease: DISEASE: Cone dystrophy 4 (COD4) [MIM:613093]: An early-onset cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs. {ECO:0000269|PubMed:19615668}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Achromatopsia 5 (ACHM5) [MIM:613093]: A form of achromatopsia, an ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus. ACHM5 inheritance is autosomal recessive. {ECO:0000269|PubMed:19615668, ECO:0000269|PubMed:21127010, ECO:0000269|PubMed:28583373}. 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 metabolism;Purine nucleotides nucleosides metabolism;Visual signal transduction: Cones (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.816
• rvis_EVS: 0.12
• rvis_percentile_EVS: 62.17

Haploinsufficiency Scores

• pHI: 0.349
• hipred: N
• hipred_score: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.189

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde6c
• Phenotype: vision/eye 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)

Zebrafish Information Network

• Gene name: pde6c
• Affected structure: ON-bipolar cell
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: visual perception;phototransduction, visible light;retinal cone cell development
• Cellular component: plasma membrane
• Molecular function: cGMP binding;metal ion binding;3',5'-cyclic-GMP phosphodiesterase activity