PDE6C (phosphodiesterase 6C)

Gene

• Entrez ID: 5146
• Gene name: Phosphodiesterase 6C
• Gene symbol: PDE6C
• Synonyms (NCBI Gene): ACHM5, COD4, PDEA2
• Chromosome: 10
• Chromosome location: 10q23.33
• Summary: This gene encodes the alpha-prime subunit of cone phosphodiesterase, which is composed of a homodimer of two alpha-prime subunits and 3 smaller proteins of 11, 13, and 15 kDa. Mutations in this gene are associated with cone dystrophy type 4 (COD4). [provi

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918537	C>A,T	Pathogenic	Synonymous variant, missense variant, coding sequence variant
rs121918538	T>A	Pathogenic	Missense variant, coding sequence variant
rs121918539	A>G	Pathogenic	Missense variant, coding sequence variant
rs140524715	A>G	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs181296577	T>C	Conflicting-interpretations-of-pathogenicity	Intron variant
rs267606934	A>G,T	Pathogenic	Coding sequence variant, missense variant
rs267606935	T>A	Pathogenic	Coding sequence variant, stop gained
rs267606936	G>A	Pathogenic	Coding sequence variant, missense variant
rs267606937	C>T	Pathogenic	Coding sequence variant, stop gained
rs374805348	G>A	Likely-pathogenic	Intron variant
rs387906401	G>C	Pathogenic	Coding sequence variant, missense variant
rs756324901	G>T	Pathogenic	Coding sequence variant, stop gained
rs757622521	C>T	Pathogenic	Coding sequence variant, stop gained
rs762152984	T>C	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs762426409	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs766703340	T>G	Likely-pathogenic	Coding sequence variant, missense variant
rs786200908	->AG	Pathogenic	Coding sequence variant, frameshift variant
rs786200909	T>A	Pathogenic	Intron variant
rs786200910	A>G	Pathogenic	Splice acceptor variant
rs786200911	->A	Pathogenic	Stop gained, coding sequence variant
rs786205462	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs786205463	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs796051871	GTAAG>-	Pathogenic, likely-pathogenic	Coding sequence variant, intron variant, splice donor variant
rs863224908	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1023522305	G>A,C	Likely-pathogenic	Splice donor variant
rs1028838062	C>T	Pathogenic	Stop gained, coding sequence variant
rs1057518244	G>T	Likely-pathogenic	Splice acceptor variant
rs1554888353	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs1554888848	A>-	Pathogenic	Frameshift variant, coding sequence variant
rs1554888858	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1554888861	G>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1554888978	A>-	Pathogenic	Frameshift variant, coding sequence variant
rs1554889905	G>A	Pathogenic	Splice donor variant
rs1554890513	AAGT>-	Likely-pathogenic	Intron variant, coding sequence variant, splice donor variant
rs1564801134	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1589690942	G>A	Pathogenic	Coding sequence variant, stop gained
rs1589693002	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1589704707	T>G	Pathogenic	Splice donor variant
rs1589705946	G>A	Pathogenic	Coding sequence variant, stop gained

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004114	Function	3',5'-cyclic-nucleotide phosphodiesterase activity	IEA
GO:0004115	Function	3',5'-cyclic-AMP phosphodiesterase activity	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007601	Process	Visual perception	IBA
GO:0007601	Process	Visual perception	IEA
GO:0007601	Process	Visual perception	IEA
GO:0007601	Process	Visual perception	TAS	8641425
GO:0007603	Process	Phototransduction, visible light	IEA
GO:0008081	Function	Phosphoric diester hydrolase activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0030553	Function	CGMP binding	IEA
GO:0046549	Process	Retinal cone cell development	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0047555	Function	3',5'-cyclic-GMP phosphodiesterase activity	IBA
GO:0047555	Function	3',5'-cyclic-GMP phosphodiesterase activity	IEA
GO:0050953	Process	Sensory perception of light stimulus	IEA
GO:0097381	Component	Photoreceptor disc membrane	IEA
GO:0141162	Process	Negative regulation of cAMP/PKA signal transduction	IBA

Other IDs

• MIM: 600827
• HGNC: 8787
• e!Ensembl: ENSG00000095464

Protein

• UniProt ID: P51160
• Protein name: Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (EC 3.1.4.35) (cGMP phosphodiesterase 6C)
• Protein function: As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP.
• PDB: 3JWQ, 3JWR, 5E8F, 9CXG, 9CXH, 9CXI, 9CXJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01590	GAF	75 → 224	GAF domain	Domain
  PF01590	GAF	256 → 433	GAF domain	Domain
  PF00233	PDEase_I	561 → 806		Domain

• Sequence:

  MGEINQVAVEKYLEENPQFAKEYFDRKLRVEVLGEIFKNSQVPVQSSMSFSELTQVEESA
  LCLELLWTVQEEGGTPEQGVHRALQRLAHLLQADRCSMFLCRSRNGIPEVASRLLDVTPT
  SKFEDNLVGPDKEVVFPLDIGIVGWAAHTKKTHNVPDVKKNSHFSDFMDKQTGYVTKNLL
  ATPIVVGKEVLAVIMAVNKVNASEFSKQDEEVFSKYLNFVSIILRLHHTSYMYNIESRRS
  QILMWSANKVFEELTDVERQFHKALYTVRSYLNCERYSIGLLDMTKEKEFYDEWPIKLGE
  VEPYKGPKTPDGREVNFYKIIDYILHGKEEIKVIPTPPADHWTLISGLPTYVAENGFICN
  MMNAPADEYFTFQKGPVDETGWVIKNVLSLPIVNKKEDIVGVATFYNRKDGKPFDEHDEY
  ITETLTQFLGWSLLNTDTYDKMNKLENRKDIAQEMLMNQTKATPEEIKSILKFQEKLNVD
  VIDDCEEKQLVAILKEDLPDPRSAELYEFRFSDFPLTEHGLIKCGIRLFFEINVVEKFKV
  PVEVLTRWMYTVRKGYRAVTYHNWRHGFNVGQTMFTLLMTGRLKKYYTDLEAFAMLAAAF
  CHDIDHRGTNNLYQMKSTSPLARLHGSSILERHHLEYSKTLLQDESLNIFQNLNKRQFET
  VIHLFEVAIIATDLALYFKKRTMFQKIVDACEQMQTEEEAIKYVTVDPTKKEIIMAMMMT
  ACDLSAITKPWEVQSQVALMVANEFWEQGDLERTVLQQQPIPMMDRNKRDELPKLQVGFI
  DFVCTFVYKEFSRFHKEITPMLSGLQNNRVEWKSLADEYDAKMKVIEEEAKKQEGGAEKA
  AEDSGGGDDKKSKTCLML

• Sequence length: 858

Pathways

KEGG:

Purine metabolism
Metabolic pathways

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of the eye	Likely pathogenic	rs2134611976	RCV001814390	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Achromatopsia	Pathogenic; Likely pathogenic	rs765296989, rs1554888858, rs1554888861, rs1023522305, rs1554890513, rs1554888353, rs756324901, rs1554888848, rs757622521, rs1554888978, rs1554889905, rs1028838062, rs766703340	RCV001591819 RCV000504665 RCV000504786 RCV000504974 RCV000505030 RCV000664193 RCV000664190 RCV000664194 RCV000664191 RCV000664195 RCV000664189 RCV000664192 RCV001003118	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Achromatopsia 5	Likely pathogenic; Pathogenic	rs121918537, rs121918538, rs786200908, rs796051871, rs121918539, rs387906401, rs267606936, rs786200909, rs786200910, rs267606934, rs267606937, rs267606935, rs786200911	RCV000761206 RCV000009309 RCV000009310 RCV000009311 RCV000009312 RCV000009313 RCV000009314 RCV000009315 RCV000009316 RCV000009317 RCV000009318 RCV000009319 RCV000009320	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Cone dystrophy	Likely pathogenic	rs1589693002	RCV001003117	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cone dystrophy 4	Likely pathogenic; Pathogenic	rs781699886, rs760343056, rs2492492590, rs958171434, rs762426409, rs374805348, rs863224908, rs121918537, rs796051871, rs2492563607, rs1410436651, rs1023522305, rs757622521, rs1028838062, rs1564801134, rs1589705946, rs1589690942, rs1589704707, rs769738331	RCV005245836 RCV002250994 RCV003108008 RCV003225999 RCV001781531 RCV005252788 RCV000199969 RCV000009308 RCV002250457 RCV002789992 RCV003314438 RCV001353003 RCV001809677 RCV005231112 RCV000735778 RCV000988436 RCV001029762 RCV001029756 RCV005909000	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Isolated macular dystrophy	Pathogenic	rs2492571833	RCV003389579	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PDE6C-related disorder	Likely pathogenic; Pathogenic	rs781699886, rs1328017393, rs1236291370	RCV003399199 RCV003401962 RCV003413900	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinal dystrophy	Likely pathogenic; Pathogenic	rs781699886, rs2492534156, rs796051871, rs2058399145, rs1403661741, rs746820022, rs1236291370, rs2058673701, rs2058440863	RCV004815515 RCV004817178 RCV004814865 RCV001073910 RCV001074365 RCV001073908 RCV001074364 RCV001075121 RCV001075713	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AMPHETAMINE OR RELATED ACTING SYMPATHOMIMETIC ABUSE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AMPHETAMINE-RELATED DISORDERS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONE-ROD DYSTROPHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cone-Rod Dystrophy, Recessive	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Optic atrophy	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
PROGRESSIVE CONE DYSTROPHY	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINITIS PIGMENTOSA 1	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Achromatopsia	Achromatopsia	ORPHANET_DG	19615668		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Achromatopsia	Achromatopsia	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Achromatopsia	Achromatopsia	BEFREE	19887631, 21127010, 25605338, 28583373, 30080950, 30667376, 31826238		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Achromatopsia	Achromatopsia	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Achromatopsia	Achromatopsia	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Achromatopsia 5	Achromatopsia	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Atrophoderma maculatum	Anetoderma	BEFREE	25605338		★☆☆☆☆ Found in Text Mining only
beta Thalassemia	Beta thalassemia	Pubtator	11074564	Associate	★☆☆☆☆ Found in Text Mining only
Color Vision Defects	Color vision deficiency	Pubtator	19615668, 22901948, 24148654, 29618791, 30080950, 31237654, 31520890, 31826238, 32306724, 32913385, 33001157, 34360608, 36833446, 36835061, 36980963, 37372476	Associate	★☆☆☆☆ Found in Text Mining only
Cone Dystrophy	Cone Dystrophy	BEFREE	10393054		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cone Dystrophy	Cone dystrophy	Pubtator	19615668, 33001157, 37433860	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
CONE DYSTROPHY 4 (disorder)	Cone Dystrophy	UNIPROT_DG	19615668, 21127010, 28583373		★☆☆☆☆ Found in Text Mining only
CONE DYSTROPHY 4 (disorder)	Cone Dystrophy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
CONE DYSTROPHY 4 (disorder)	Cone Dystrophy	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
CONE DYSTROPHY 4 (disorder)	Cone Dystrophy	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Cone monochromatism	Cone monochromatism	BEFREE	19615668		★☆☆☆☆ Found in Text Mining only
Cone monochromatism	Cone monochromatism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cone-Rod Dystrophies	Cone-rod dystrophy	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Disorder of eye	Disorder Of Eye	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Dyschromatopsia	Dyschromatopsia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Exotropia	Exotropia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperopia	Hyperopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	Pubtator	31826238, 36980963	Associate	★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus Pathologic	Nystagmus	Pubtator	31826238, 33001157	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	40240887	Associate	★☆☆☆☆ Found in Text Mining only
Pendular Nystagmus	Pendular nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Progressive Cone Dystrophy	Cone Dystrophy	BEFREE	19615668		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Progressive cone dystrophy	Cone Dystrophy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Progressive cone dystrophy (without rod involvement)	Progressive Cone Dystrophy	ORPHANET_DG	19615668		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	25979379	Associate	★☆☆☆☆ Found in Text Mining only
Retinal Diseases	Retinal Diseases	BEFREE	10393054, 31826238		★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis pigmentosa	Pubtator	37165311	Associate	★☆☆☆☆ Found in Text Mining only
RHYNS syndrome	Rhyns syndrome	Pubtator	37165311	Associate	★☆☆☆☆ Found in Text Mining only
Usher Syndromes	Usher syndrome	Pubtator	37165311	Associate	★☆☆☆☆ Found in Text Mining only
Vision Disorders	Visual disorder	Pubtator	31520890, 36980963	Associate	★☆☆☆☆ Found in Text Mining only