Seroatlas · Human Serome Atlas

CACNA1A

Voltage-dependent P/Q-type calcium channel subunit alpha-1A

Also known as: APCA, CAC1A_HUMAN, CACNL1A4, Cav2.1, EA2, FHM, HPCA, MHP, MHP1, SCA6

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: O00555
Gene: CACNA1A
Ensembl: ENSG00000141837
Chromosome: 19
Canonical length: 2506 aa
Protein class: Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters, Voltage-gated ion channels
Subcellular location: Endoplasmic reticulum

OverviewNCBI Gene

Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-18 to 21-33 in the coding region is associated with spinocerebellar ataxia 6. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

2506 residues, UniProt reviewed canonical sequence.

>O00555|CACNA1A
     1  MARFGDEMPA RYGGGGSGAA AGVVVGSGGG RGAGGSRQGG QPGAQRMYKQ SMAQRARTMA
    61  LYNPIPVRQN CLTVNRSLFL FSEDNVVRKY AKKITEWPPF EYMILATIIA NCIVLALEQH
   121  LPDDDKTPMS ERLDDTEPYF IGIFCFEAGI KIIALGFAFH KGSYLRNGWN VMDFVVVLTG
   181  ILATVGTEFD LRTLRAVRVL RPLKLVSGIP SLQVVLKSIM KAMIPLLQIG LLLFFAILIF
   241  AIIGLEFYMG KFHTTCFEEG TDDIQGESPA PCGTEEPART CPNGTKCQPY WEGPNNGITQ
   301  FDNILFAVLT VFQCITMEGW TDLLYNSNDA SGNTWNWLYF IPLIIIGSFF MLNLVLGVLS
   361  GEFAKERERV ENRRAFLKLR RQQQIERELN GYMEWISKAE EVILAEDETD GEQRHPFDAL
   421  RRTTIKKSKT DLLNPEEAED QLADIASVGS PFARASIKSA KLENSTFFHK KERRMRFYIR
   481  RMVKTQAFYW TVLSLVALNT LCVAIVHYNQ PEWLSDFLYY AEFIFLGLFM SEMFIKMYGL
   541  GTRPYFHSSF NCFDCGVIIG SIFEVIWAVI KPGTSFGISV LRALRLLRIF KVTKYWASLR
   601  NLVVSLLNSM KSIISLLFLL FLFIVVFALL GMQLFGGQFN FDEGTPPTNF DTFPAAIMTV
   661  FQILTGEDWN EVMYDGIKSQ GGVQGGMVFS IYFIVLTLFG NYTLLNVFLA IAVDNLANAQ
   721  ELTKDEQEEE EAANQKLALQ KAKEVAEVSP LSAANMSIAV KEQQKNQKPA KSVWEQRTSE
   781  MRKQNLLASR EALYNEMDPD ERWKAAYTRH LRPDMKTHLD RPLVVDPQEN RNNNTNKSRA
   841  AEPTVDQRLG QQRAEDFLRK QARYHDRARD PSGSAGLDAR RPWAGSQEAE LSREGPYGRE
   901  SDHHAREGSL EQPGFWEGEA ERGKAGDPHR RHVHRQGGSR ESRSGSPRTG ADGEHRRHRA
   961  HRRPGEEGPE DKAERRARHR EGSRPARGGE GEGEGPDGGE RRRRHRHGAP ATYEGDARRE
  1021  DKERRHRRRK ENQGSGVPVS GPNLSTTRPI QQDLGRQDPP LAEDIDNMKN NKLATAESAA
  1081  PHGSLGHAGL PQSPAKMGNS TDPGPMLAIP AMATNPQNAA SRRTPNNPGN PSNPGPPKTP
  1141  ENSLIVTNPS GTQTNSAKTA RKPDHTTVDI PPACPPPLNH TVVQVNKNAN PDPLPKKEEE
  1201  KKEEEEDDRG EDGPKPMPPY SSMFILSTTN PLRRLCHYIL NLRYFEMCIL MVIAMSSIAL
  1261  AAEDPVQPNA PRNNVLRYFD YVFTGVFTFE MVIKMIDLGL VLHQGAYFRD LWNILDFIVV
  1321  SGALVAFAFT GNSKGKDINT IKSLRVLRVL RPLKTIKRLP KLKAVFDCVV NSLKNVFNIL
  1381  IVYMLFMFIF AVVAVQLFKG KFFHCTDESK EFEKDCRGKY LLYEKNEVKA RDREWKKYEF
  1441  HYDNVLWALL TLFTVSTGEG WPQVLKHSVD ATFENQGPSP GYRMEMSIFY VVYFVVFPFF
  1501  FVNIFVALII ITFQEQGDKM MEEYSLEKNE RACIDFAISA KPLTRHMPQN KQSFQYRMWQ
  1561  FVVSPPFEYT IMAMIALNTI VLMMKFYGAS VAYENALRVF NIVFTSLFSL ECVLKVMAFG
  1621  ILNYFRDAWN IFDFVTVLGS ITDILVTEFG NNFINLSFLR LFRAARLIKL LRQGYTIRIL
  1681  LWTFVQSFKA LPYVCLLIAM LFFIYAIIGM QVFGNIGIDV EDEDSDEDEF QITEHNNFRT
  1741  FFQALMLLFR SATGEAWHNI MLSCLSGKPC DKNSGILTRE CGNEFAYFYF VSFIFLCSFL
  1801  MLNLFVAVIM DNFEYLTRDS SILGPHHLDE YVRVWAEYDP AAWGRMPYLD MYQMLRHMSP
  1861  PLGLGKKCPA RVAYKRLLRM DLPVADDNTV HFNSTLMALI RTALDIKIAK GGADKQQMDA
  1921  ELRKEMMAIW PNLSQKTLDL LVTPHKSTDL TVGKIYAAMM IMEYYRQSKA KKLQAMREEQ
  1981  DRTPLMFQRM EPPSPTQEGG PGQNALPSTQ LDPGGALMAH ESGLKESPSW VTQRAQEMFQ
  2041  KTGTWSPEQG PPTDMPNSQP NSQSVEMREM GRDGYSDSEH YLPMEGQGRA ASMPRLPAEN
  2101  QRRRGRPRGN NLSTISDTSP MKRSASVLGP KARRLDDYSL ERVPPEENQR HHQRRRDRSH
  2161  RASERSLGRY TDVDTGLGTD LSMTTQSGDL PSKERDQERG RPKDRKHRQH HHHHHHHHHP
  2221  PPPDKDRYAQ ERPDHGRARA RDQRWSRSPS EGREHMAHRQ GSSSVSGSPA PSTSGTSTPR
  2281  RGRRQLPQTP STPRPHVSYS PVIRKAGGSG PPQQQQQQQQ QQQQQAVARP GRAATSGPRR
  2341  YPGPTAEPLA GDRPPTGGHS SGRSPRMERR VPGPARSESP RACRHGGARW PASGPHVSEG
  2401  PPGPRHHGYY RGSDYDEADG PGSGGGEEAM AGAYDAPPPV RHASSGATGR SPRTPRASGP
  2461  ACASPSRHGR RLPNGYYPAH GLARPRGPGS RKGLHEPYSE SDDDWC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CACNA1A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 24
Mean surface accessibility (rSASA): 0.43
Highest tissue expression: 286 nTPM

Expression across tissuesHPA

Tissue

cerebellum: 286 nTPM
cerebral cortex: 37 nTPM
basal ganglia: 29 nTPM
amygdala: 21 nTPM
hippocampal formation: 19 nTPM
hypothalamus: 16 nTPM

Single-cell type

neuroendocrine cells: 1,661 nCPM
retinal horizontal cells: 1,336 nCPM
retinal amacrine cells: 1,020 nCPM
pancreatic islet cells: 859 nCPM
oligodendrocyte progenitor cells: 737 nCPM
brain excitatory neurons: 663 nCPM

Immune cell

memory B-cell: 0.5 nTPM
basophil: 0.4 nTPM
naive B-cell: 0.3 nTPM
neutrophil: 0.2 nTPM
non-classical monocyte: 0.2 nTPM
eosinophil: 0.1 nTPM

Brain region

cerebellum: 218 nTPM
cerebral cortex: 76 nTPM
amygdala: 44 nTPM
white matter: 43 nTPM
basal ganglia: 41 nTPM
hippocampal formation: 37 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CACNA1A.

Disease | AllUniProt

Conditions CACNA1A is implicated in, by any mechanism.

Spinocerebellar ataxia 6 (SCA6) MIM:183086
Migraine, familial hemiplegic, 1 (FHM1) MIM:141500
Episodic ataxia 2 (EA2) MIM:108500
Developmental and epileptic encephalopathy 42 (DEE42) MIM:617106

Disease | GeneticClinVar

570 pathogenic / likely-pathogenic of 4,438 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Episodic ataxia type 2
Developmental and epileptic encephalopathy, 42
Spinocerebellar ataxia type 6
Migraine, familial hemiplegic, 1
Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.13
gnomAD pLI: 1
gnomAD missense Z: 5.78
DepMap mean gene effect: -0.08
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CACNA1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CACNA1A as an antibody target. Whether an autoantibody or antibody against CACNA1A could matter depends on whether native CACNA1A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CACNA1A is annotated at the cell surface, where native CACNA1A is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label CACNA1A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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