CNGA1 (cyclic nucleotide gated channel subunit alpha 1)

Gene

• Entrez ID: 1259
• Gene name: Cyclic nucleotide gated channel subunit alpha 1
• Gene symbol: CNGA1
• Synonyms (NCBI Gene): CNCG, CNCG1, CNG-1, CNG1, RCNC1, RCNCa, RCNCalpha, RP49
• Chromosome: 4
• Chromosome location: 4p12
• Summary: The protein encoded by this gene is involved in phototransduction. Along with another protein, the encoded protein forms a cGMP-gated cation channel in the plasma membrane, allowing depolarization of rod photoreceptors. This represents the last step in th

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT899509	hsa-miR-2053	CLIP-seq
MIRT899510	hsa-miR-4501	CLIP-seq
MIRT899511	hsa-miR-548c-3p	CLIP-seq
MIRT899512	hsa-miR-569	CLIP-seq
MIRT2436274	hsa-miR-4778-3p	CLIP-seq
MIRT2436275	hsa-miR-513a-3p	CLIP-seq
MIRT2436276	hsa-miR-590-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0001750	Component	Photoreceptor outer segment	IEA
GO:0005216	Function	Monoatomic ion channel activity	IEA
GO:0005221	Function	Intracellularly cyclic nucleotide-activated monoatomic cation channel activity	IEA
GO:0005222	Function	Intracellularly cAMP-activated cation channel activity	IBA
GO:0005222	Function	Intracellularly cAMP-activated cation channel activity	IDA	34699778
GO:0005223	Function	Intracellularly cGMP-activated cation channel activity	IBA
GO:0005223	Function	Intracellularly cGMP-activated cation channel activity	IDA	34699778
GO:0005262	Function	Calcium channel activity	IEA
GO:0005272	Function	Sodium channel activity	IEA
GO:0005515	Function	Protein binding	IPI	20890309
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	7479749
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006814	Process	Sodium ion transport	IEA
GO:0006814	Process	Sodium ion transport	ISS
GO:0006816	Process	Calcium ion transport	IEA
GO:0006816	Process	Calcium ion transport	ISS
GO:0007601	Process	Visual perception	IEA
GO:0007601	Process	Visual perception	TAS	7479749
GO:0007606	Process	Sensory perception of chemical stimulus	IBA
GO:0016020	Component	Membrane	IEA
GO:0017071	Component	Intracellular cyclic nucleotide activated cation channel complex	IBA
GO:0030552	Function	CAMP binding	IDA	34699778
GO:0030552	Function	CAMP binding	IEA
GO:0030553	Function	CGMP binding	IBA
GO:0030553	Function	CGMP binding	IDA	34699778
GO:0030553	Function	CGMP binding	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0035725	Process	Sodium ion transmembrane transport	IEA
GO:0042622	Component	Photoreceptor outer segment membrane	IEA
GO:0055085	Process	Transmembrane transport	IEA
GO:0070588	Process	Calcium ion transmembrane transport	IEA
GO:0098655	Process	Monoatomic cation transmembrane transport	IBA
GO:0120200	Component	Rod photoreceptor outer segment	IEA
GO:0120200	Component	Rod photoreceptor outer segment	ISS

Other IDs

• MIM: 123825
• HGNC: 2148
• e!Ensembl: ENSG00000198515

Protein

• UniProt ID: P29973
• Protein name: Cyclic nucleotide-gated channel alpha-1 (CNG channel alpha-1) (CNG-1) (CNG1) (Cyclic nucleotide-gated channel, photoreceptor) (Rod photoreceptor cGMP-gated cation channel subunit alpha) (cGMP-gated cation channel alpha-1)
• Protein function: Pore-forming subunit of the rod cyclic nucleotide-gated channel. Mediates rod photoresponses at dim light converting transient changes in intracellular cGMP levels into electrical signals. In the dark, cGMP levels are high and keep the channel o
• PDB: 7LFT, 7LFW, 7LFX, 7LFY, 7LG1, 7RH9, 7RHG, 7RHH, 7RHI, 7RHJ, 7RHK, 7RHL
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00520	Ion_trans	164 → 408	Ion transport protein	Family
  PF00027	cNMP_binding	497 → 588	Cyclic nucleotide-binding domain	Domain
  PF16526	CLZ	595 → 665	C-terminal leucine zipper domain of cyclic nucleotide-gated channels	Coiled-coil

• Tissue specificity: TISSUE SPECIFICITY: Rod cells in the retina.
• Sequence:

  MKLSMKNNIINTQQSFVTMPNVIVPDIEKEIRRMENGACSSFSEDDDSASTSEESENENP
  HARGSFSYKSLRKGGPSQREQYLPGAIALFNVNNSSNKDQEPEEKKKKKKEKKSKSDDKN
  ENKNDPEKKKKKKDKEKKKKEEKSKDKKEEEKKEVVVIDPSGNTYYNWLFCITLPVMYNW
  TMVIARACFDELQSDYLEYWLILDYVSDIVYLIDMFVRTRTGYLEQGLLVKEELKLINKY
  KSNLQFKLDVLSLIPTDLLYFKLGWNYPEIRLNRLLRFSRMFEFFQRTETRTNYPNIFRI
  SNLVMYIVIIIHWNACVFYSISKAIGFGNDTWVYPDINDPEFGRLARKYVYSLYWSTLTL
  TTIGETPPPVRDSEYVFVVVDFLIGVLIFATIVGNIGSMISNMNAARAEFQARIDAIKQY
  MHFRNVSKDMEKRVIKWFDYLWTNKKTVDEKEVLKYLPDKLRAEIAINVHLDTLKKVRIF
  ADCEAGLLVELVLKLQPQVYSPGDYICKKGDIGREMYIIKEGKLAVVADDGVTQFVVLSD
  GSYFGEISILNIKGSKAGNRRTANIKSIGYSDLFCLSKDDLMEALTEYPDAKTMLEEKGK
  QILMKDGLLDLNIANAGSDPKDLEEKVTRMEGSVDLLQTRFARILAEYESMQQKLKQRLT
  KVEKFLKPLIDTEFSSIEGPGAESGPIDST

• Sequence length: 690

Pathways

KEGG:

cGMP-PKG signaling pathway
cAMP signaling pathway
Phototransduction

Reactome:

Activation of the phototransduction cascade
Inactivation, recovery and regulation of the phototransduction cascade

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
CNGA1-related disorder	Pathogenic; Likely pathogenic	rs1428479359, rs1436425494, rs62625014, rs772867912, rs1237954156	RCV004757423 RCV004757474 RCV004757110 RCV004757366 RCV004757374	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
CNGA1-related retinopathy	Pathogenic	rs544588016	RCV005361586	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cone-rod dystrophy	Likely pathogenic; Pathogenic	rs62625014	RCV000787818	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Macular dystrophy	Likely pathogenic; Pathogenic	rs62625014	RCV000787817	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinal dystrophy	Pathogenic; Likely pathogenic	rs759781200, rs749012133, rs199584830, rs2475748768, rs62625014, rs199636364, rs772867912, rs768694789, rs1738673948, rs1738698692, rs369717052, rs1237954156	RCV004816449 RCV001073700 RCV000225417 RCV003890926 RCV001073687 RCV001075248 RCV001073750 RCV001073711 RCV001074497 RCV001075232 RCV001075049 RCV001075406	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinitis pigmentosa	Pathogenic; Likely pathogenic	rs910102517, rs1436425494, rs527236059, rs527236058, rs759781200, rs749012133, rs199584830, rs62625014, rs567961453, rs199636364, rs1037963003, rs1578059695, rs759079269, rs1560621807, rs1738719686, rs867483436, rs768694789	RCV005408884 RCV001724853 RCV000132618 RCV000132620 RCV000987444 RCV002500683 RCV000505102 RCV000778730 RCV000504735 RCV001002956 RCV000987445 RCV001002952 RCV001002953 RCV001002955 RCV001199460 RCV001199457 RCV001724230	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinitis pigmentosa 49	Likely pathogenic; Pathogenic	rs2110127572, rs544588016, rs1436425494, rs1246377488, rs1443039086, rs527236058, rs539600817, rs1738701040, rs777235692, rs759781200, rs749012133, rs199584830, rs2475768684, rs2475768752, rs2475816188, rs2475748633, rs764086464, rs121909599, rs121909600, rs62625014, rs2475745208, rs199636364, rs767994904, rs772867912, rs1476546899, rs768694789, rs1237954156, rs376959147	RCV001376507 RCV003222314 RCV005235589 RCV005031999 RCV005031990 RCV000490404 RCV003447619 RCV003222462 RCV005034443 RCV001376331 RCV000490509 RCV001376521 RCV003152541 RCV003152546 RCV003227543 RCV003389598 RCV005036919 RCV000018438 RCV000018439 RCV000018440 RCV000018441 RCV000662351 RCV005036103 RCV005036349 RCV005036352 RCV005036387 RCV005036391 RCV005005123	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
COLONIC NEOPLASM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONE-ROD DYSTROPHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Optic atrophy	Benign	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Prostate cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINITIS PIGMENTOSA 1	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Retinitis Pigmentosa, Recessive	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPONDYLOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cone-Rod Dystrophies	Cone-rod dystrophy	CLINVAR_DG	30718709		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital hypoplasia of penis	Congenital Hypoplasia Of Penis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetic Retinopathy	Diabetic retinopathy	Pubtator	37318461	Associate	★☆☆☆☆ Found in Text Mining only
Disorder of eye	Disorder Of Eye	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	24732025		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Keratoconus	Keratoconus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Macular dystrophy	Macular dystrophy	CLINVAR_DG	30718709		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Nyctalopia	Nyctalopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	HPO_DG			★☆☆☆☆ Found in Text Mining only
obsolete Rod-cone dystrophy	Rod-cone dystrophy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Parkinson Disease	Parkinson disease	BEFREE	29989488		★☆☆☆☆ Found in Text Mining only
Retinal Diseases	Retinal detachment	Pubtator	25775262, 31877759	Associate	★☆☆☆☆ Found in Text Mining only
Retinal Dystrophies	Retinal Dystrophy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	LHGDN	12362048, 15570217		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinitis Pigmentosa	Retinitis pigmentosa	Pubtator	15570217, 25268133, 26802146, 27391953, 31960602, 32705276, 33633220, 35814500, 38340451	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinitis pigmentosa	Retinitis Pigmentosa	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	BEFREE	20950332, 26802146		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	CLINVAR_DG	24265693, 25611614, 26306921, 28981474, 30718709, 7479749		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	CTD_human_DG	7479749		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RETINITIS PIGMENTOSA 49	Retinitis Pigmentosa	UNIPROT_DG	15570217, 7479749		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RETINITIS PIGMENTOSA 49	Retinitis Pigmentosa	CLINVAR_DG	23462753, 25268133, 7479749		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RETINITIS PIGMENTOSA 49	Retinitis Pigmentosa	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
RETINITIS PIGMENTOSA 49	Retinitis Pigmentosa	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Rod-Cone Dystrophy	Rod-cone dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only