CACNA2D4 (calcium voltage-gated channel auxiliary subunit alpha2delta 4)

Gene

• Entrez ID: 93589
• Gene name: Calcium voltage-gated channel auxiliary subunit alpha2delta 4
• Gene symbol: CACNA2D4
• Synonyms (NCBI Gene): RCD4
• Chromosome: 12
• Chromosome location: 12p13.33
• Summary: This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, a

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs71454844	G>A,T	Likely-pathogenic, uncertain-significance	Synonymous variant, stop gained, coding sequence variant
rs76064926	C>T	Benign, likely-pathogenic, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs77175207	C>G,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, missense variant
rs199888783	G>A,C	Conflicting-interpretations-of-pathogenicity	Missense variant, synonymous variant, coding sequence variant
rs200098356	G>A,C	Uncertain-significance, likely-pathogenic	Missense variant, stop gained, coding sequence variant
rs201783863	C>A,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs1210621191	GCCCAGC>-	Likely-pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017574	hsa-miR-335-5p	Microarray	18185580
MIRT449485	hsa-miR-7158-3p	PAR-CLIP	22100165
MIRT449484	hsa-miR-203b-3p	PAR-CLIP	22100165
MIRT449485	hsa-miR-7158-3p	PAR-CLIP	22100165
MIRT449484	hsa-miR-203b-3p	PAR-CLIP	22100165
MIRT857832	hsa-miR-1179	CLIP-seq
MIRT857833	hsa-miR-320e	CLIP-seq
MIRT857834	hsa-miR-3945	CLIP-seq
MIRT857835	hsa-miR-4252	CLIP-seq
MIRT857836	hsa-miR-4259	CLIP-seq
MIRT857837	hsa-miR-4260	CLIP-seq
MIRT857838	hsa-miR-4715-5p	CLIP-seq
MIRT857839	hsa-miR-4727-5p	CLIP-seq
MIRT857840	hsa-miR-4769-3p	CLIP-seq
MIRT857841	hsa-miR-4778-5p	CLIP-seq
MIRT857842	hsa-miR-486-3p	CLIP-seq
MIRT1954742	hsa-miR-1294	CLIP-seq
MIRT1954743	hsa-miR-4316	CLIP-seq
MIRT1954744	hsa-miR-4675	CLIP-seq
MIRT1954745	hsa-miR-4687-3p	CLIP-seq
MIRT1954746	hsa-miR-4741	CLIP-seq
MIRT1954747	hsa-miR-5096	CLIP-seq
MIRT2192313	hsa-miR-15a	CLIP-seq
MIRT2192314	hsa-miR-15b	CLIP-seq
MIRT2192315	hsa-miR-16	CLIP-seq
MIRT2192316	hsa-miR-195	CLIP-seq
MIRT2192317	hsa-miR-3144-5p	CLIP-seq
MIRT2192318	hsa-miR-3191	CLIP-seq
MIRT2192319	hsa-miR-3913-3p	CLIP-seq
MIRT857834	hsa-miR-3945	CLIP-seq
MIRT2192320	hsa-miR-424	CLIP-seq
MIRT857836	hsa-miR-4259	CLIP-seq
MIRT857837	hsa-miR-4260	CLIP-seq
MIRT2192321	hsa-miR-4524	CLIP-seq
MIRT2192322	hsa-miR-4652-5p	CLIP-seq
MIRT857838	hsa-miR-4715-5p	CLIP-seq
MIRT2192323	hsa-miR-4747-5p	CLIP-seq
MIRT857842	hsa-miR-486-3p	CLIP-seq
MIRT2192324	hsa-miR-497	CLIP-seq
MIRT2192325	hsa-miR-499-3p	CLIP-seq
MIRT2192326	hsa-miR-499a-3p	CLIP-seq
MIRT2192327	hsa-miR-503	CLIP-seq
MIRT2192328	hsa-miR-646	CLIP-seq
MIRT857834	hsa-miR-3945	CLIP-seq
MIRT857836	hsa-miR-4259	CLIP-seq
MIRT857837	hsa-miR-4260	CLIP-seq
MIRT857838	hsa-miR-4715-5p	CLIP-seq
MIRT857842	hsa-miR-486-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005245	Function	Voltage-gated calcium channel activity	IBA
GO:0005245	Function	Voltage-gated calcium channel activity	IDA	12181424
GO:0005262	Function	Calcium channel activity	IEA
GO:0005891	Component	Voltage-gated calcium channel complex	IBA
GO:0005891	Component	Voltage-gated calcium channel complex	IDA	12181424
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006816	Process	Calcium ion transport	IEA
GO:0016020	Component	Membrane	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034702	Component	Monoatomic ion channel complex	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0050908	Process	Detection of light stimulus involved in visual perception	IMP	17033974
GO:0070588	Process	Calcium ion transmembrane transport	IDA	12181424
GO:0070588	Process	Calcium ion transmembrane transport	IEA

Other IDs

• MIM: 608171
• HGNC: 20202
• e!Ensembl: ENSG00000151062

Protein

• UniProt ID: Q7Z3S7
• Protein name: Voltage-dependent calcium channel subunit alpha-2/delta-4 (Voltage-gated calcium channel subunit alpha-2/delta-4) [Cleaved into: Voltage-dependent calcium channel subunit alpha-2-4; Voltage-dependent calcium channel subunit delta-4]
• Protein function: The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08399	VWA_N	148 → 264	VWA N-terminal	Family
  PF13768	VWA_3	290 → 455	von Willebrand factor type A domain	Domain
  PF08473	VGCC_alpha2	681 → 1110	Neuronal voltage-dependent calcium channel alpha 2acd	Family

• Tissue specificity: TISSUE SPECIFICITY: Predominantly expressed in certain types of endocrine cells. Present in the Paneth cells of the small intestine. Also present in the erythroblasts in the fetal liver, in the cells of the zona reticularis of the adrenal gland and in the
• Sequence:

  MVCGCSALLPLPNPRPTMPATPNFLANPSSSSRWIPLQPMPVAWAFVQKTSALLWLLLLG
  TSLSPAWGQAKIPLETVKLWADTFGGDLYNTVTKYSGSLLLQKKYKDVESSLKIEEVDGL
  ELVRKFSEDMENMLRRKVEAVQNLVEAAEEADLNHEFNESLVFDYYNSVLINERDEKGNF
  VELGAEFLLESNAHFSNLPVNTSISSVQLPTNVYNKDPDILNGVYMSEALNAVFVENFQR
  DPTLTWQYFGSATGFFRIYPGIKWTPDENGVITFDCRNRGWYIQAATSPKDIVILVDVSG
  SMKGLRMTIAKHTITTILDTLGENDFINIIAYNDYVHYIEPCFKGILVQADRDNREHFKL
  LVEELMVKGVGVVDQALREAFQILKQFQEAKQGSLCNQAIMLISDGAVEDYEPVFEKYNW
  PDCKVRVFTYLIGREVSFADRMKWIACNNKGYYTQISTLADTQENVMEYLHVLSRPMVIN
  HDHDIIWTEAYMDSKLLSSQAQSLTLLTTVAMPVFSKKNETRSHGILLGVVGSDVALREL
  MKLAPRYKLGVHGYAFLNTNNGYILSHPDLRPLYREGKKLKPKPNYNSVDLSEVEWEDQA
  ESLRTAMINRETGTLSMDVKVPMDKGKRVLFLTNDYFFTDISDTPFSLGVVLSRGHGEYI
  LLGNTSVEEGLHDLLHPDLALAGDWIYCITDIDPDHRKLSQLEAMIRFLTRKDPDLECDE
  ELVREVLFDAVVTAPMEAYWTALALNMSEESEHVVDMAFLGTRAGLLRSSLFVGSEKVSD
  RKFLTPEDEASVFTLDRFPLWYRQASEHPAGSFVFNLRWAEGPESAGEPMVVTASTAVAV
  TVDKRTAIAAAAGVQMKLEFLQRKFWAATRQCSTVDGPCTQSCEDSDLDCFVIDNNGFIL
  ISKRSRETGRFLGEVDGAVLTQLLSMGVFSQVTMYDYQAMCKPSSHHHSAAQPLVSPISA
  FLTATRWLLQELVLFLLEWSVWGSWYDRGAEAKSVFHHSHKHKKQDPLQPCDTEYPVFVY
  QPAIREANGIVECGPCQKVFVVQQIPNSNLLLLVTDPTCDCSIFPPVLQEATEVKYNASV
  KCDRMRSQKLRRRPDSCHAFHPEENAQDCGGASDTSASPPLLLLPVCAWGLLPQLLR

• Sequence length: 1137

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)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Abnormality of the eye	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CACNA2D4-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CACNA2D4-related retinopathy	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONE DYSTROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cone dystrophy 3	Benign; Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CONE ROD DYSTROPHY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONE-ROD DYSTROPHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONE-ROD DYSTROPHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cone-rod dystrophy 6	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	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	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Progressive cone dystrophy (without rod involvement)	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Retinal cone dystrophy 4	Conflicting classifications of pathogenicity; Benign; Likely benign; Uncertain significance	ClinVar CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO CTD, ClinVar, Disgenet, GWAS catalog, HPO	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Retinal disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Retinal dystrophy	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Retinitis pigmentosa	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
RETINITIS PIGMENTOSA 1	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arteriosclerosis	Arteriosclerosis	BEFREE	31804889		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	31804889		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	BEFREE	24727801		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	24727801	Associate	★☆☆☆☆ Found in Text Mining only
Borderline Personality Disorder	Borderline personality disorder	BEFREE	22488967		★☆☆☆☆ Found in Text Mining only
Bronchopulmonary Dysplasia	Bronchopulmonary Dysplasia	BEFREE	22488967		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	31510946	Associate	★☆☆☆☆ Found in Text Mining only
Cone Dystrophy	Cone Dystrophy	BEFREE	17033974		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cone rod dystrophy	Cone-rod dystrophy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cone-Rod Dystrophies	Cone-rod dystrophy	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cone-Rod Dystrophy 2	Cone-rod dystrophy	ORPHANET_DG	17033974		★☆☆☆☆ Found in Text Mining only
Congenital stationary night blindness	Congenital stationary night blindness	Orphanet			★☆☆☆☆ Found in Text Mining only
Diabetes Gestational	Gestational diabetes	Pubtator	35721735	Associate	★☆☆☆☆ Found in Text Mining only
Disorder of eye	Disorder Of Eye	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Hypocalcemia	Hypocalcemia	Pubtator	31510946	Associate	★☆☆☆☆ Found in Text Mining only
Hypoplasia of optic disc	Hypoplasia Of Optic Disc	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mental disorders	Mental Disorders	BEFREE	22488967		★☆☆☆☆ Found in Text Mining only
Night blindness congenital stationary	Night blindness, congenital stationary	Pubtator	19578023	Associate	★☆☆☆☆ Found in Text Mining only
Night blindness, congenital stationary	Night blindness	ORPHANET_DG	19578023		★☆☆☆☆ Found in Text Mining only
Night blindness, congenital stationary	Night blindness	BEFREE	26368928		★☆☆☆☆ Found in Text Mining only
Night blindness, congenital stationary	Night blindness	GENOMICS_ENGLAND_DG	26560832		★☆☆☆☆ Found in Text Mining only
Nyctalopia	Nyctalopia	BEFREE	17033974		★☆☆☆☆ Found in Text Mining only
Nyctalopia	Nyctalopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pituitary Neoplasms	Pituitary neoplasm	Pubtator	32224525, 33168897	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	36178085	Associate	★☆☆☆☆ Found in Text Mining only
RETINAL CONE DYSTROPHY 4	Retinal Cone Dystrophy	GENOMICS_ENGLAND_DG	26560832		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
RETINAL CONE DYSTROPHY 4	Retinal Cone Dystrophy	CTD_human_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
RETINAL CONE DYSTROPHY 4	Retinal Cone Dystrophy	CLINVAR_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Severe myopia	Myopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only