Seroatlas · Human Serome Atlas

CACNA1C

Voltage-dependent L-type calcium channel subunit alpha-1C

Also known as: CAC1C_HUMAN, CACH2, CACN2, CACNL1A1, Cav1.2, CCHL1A1, LQT8, TS

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

Protein identityUniProt · HPA

UniProt accession: Q13936
Gene: CACNA1C
Ensembl: ENSG00000151067
Chromosome: 12
Canonical length: 2221 aa
Protein class: Disease related genes, FDA approved drug targets, Human disease related genes, Predicted membrane proteins, Transporters, Voltage-gated ion channels
Subcellular location: Nucleoplasm,Plasma membrane,Primary cilium

OverviewNCBI Gene

This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]

Canonical amino-acid sequenceUniProt

2221 residues, UniProt reviewed canonical sequence.

>Q13936|CACNA1C
     1  MVNENTRMYI PEENHQGSNY GSPRPAHANM NANAAAGLAP EHIPTPGAAL SWQAAIDAAR
    61  QAKLMGSAGN ATISTVSSTQ RKRQQYGKPK KQGSTTATRP PRALLCLTLK NPIRRACISI
   121  VEWKPFEIII LLTIFANCVA LAIYIPFPED DSNATNSNLE RVEYLFLIIF TVEAFLKVIA
   181  YGLLFHPNAY LRNGWNLLDF IIVVVGLFSA ILEQATKADG ANALGGKGAG FDVKALRAFR
   241  VLRPLRLVSG VPSLQVVLNS IIKAMVPLLH IALLVLFVII IYAIIGLELF MGKMHKTCYN
   301  QEGIADVPAE DDPSPCALET GHGRQCQNGT VCKPGWDGPK HGITNFDNFA FAMLTVFQCI
   361  TMEGWTDVLY WVNDAVGRDW PWIYFVTLII IGSFFVLNLV LGVLSGEFSK EREKAKARGD
   421  FQKLREKQQL EEDLKGYLDW ITQAEDIDPE NEDEGMDEEK PRNMSMPTSE TESVNTENVA
   481  GGDIEGENCG ARLAHRISKS KFSRYWRRWN RFCRRKCRAA VKSNVFYWLV IFLVFLNTLT
   541  IASEHYNQPN WLTEVQDTAN KALLALFTAE MLLKMYSLGL QAYFVSLFNR FDCFVVCGGI
   601  LETILVETKI MSPLGISVLR CVRLLRIFKI TRYWNSLSNL VASLLNSVRS IASLLLLLFL
   661  FIIIFSLLGM QLFGGKFNFD EMQTRRSTFD NFPQSLLTVF QILTGEDWNS VMYDGIMAYG
   721  GPSFPGMLVC IYFIILFICG NYILLNVFLA IAVDNLADAE SLTSAQKEEE EEKERKKLAR
   781  TASPEKKQEL VEKPAVGESK EEKIELKSIT ADGESPPATK INMDDLQPNE NEDKSPYPNP
   841  ETTGEEDEEE PEMPVGPRPR PLSELHLKEK AVPMPEASAF FIFSSNNRFR LQCHRIVNDT
   901  IFTNLILFFI LLSSISLAAE DPVQHTSFRN HILFYFDIVF TTIFTIEIAL KILGNADYVF
   961  TSIFTLEIIL KMTAYGAFLH KGSFCRNYFN ILDLLVVSVS LISFGIQSSA INVVKILRVL
  1021  RVLRPLRAIN RAKGLKHVVQ CVFVAIRTIG NIVIVTTLLQ FMFACIGVQL FKGKLYTCSD
  1081  SSKQTEAECK GNYITYKDGE VDHPIIQPRS WENSKFDFDN VLAAMMALFT VSTFEGWPEL
  1141  LYRSIDSHTE DKGPIYNYRV EISIFFIIYI IIIAFFMMNI FVGFVIVTFQ EQGEQEYKNC
  1201  ELDKNQRQCV EYALKARPLR RYIPKNQHQY KVWYVVNSTY FEYLMFVLIL LNTICLAMQH
  1261  YGQSCLFKIA MNILNMLFTG LFTVEMILKL IAFKPKGYFS DPWNVFDFLI VIGSIIDVIL
  1321  SETNHYFCDA WNTFDALIVV GSIVDIAITE VNPAEHTQCS PSMNAEENSR ISITFFRLFR
  1381  VMRLVKLLSR GEGIRTLLWT FIKSFQALPY VALLIVMLFF IYAVIGMQVF GKIALNDTTE
  1441  INRNNNFQTF PQAVLLLFRC ATGEAWQDIM LACMPGKKCA PESEPSNSTE GETPCGSSFA
  1501  VFYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH HLDEFKRIWA EYDPEAKGRI
  1561  KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVSMNMPLNS DGTVMFNATL FALVRTALRI
  1621  KTEGNLEQAN EELRAIIKKI WKRTSMKLLD QVVPPAGDDE VTVGKFYATF LIQEYFRKFK
  1681  KRKEQGLVGK PSQRNALSLQ AGLRTLHDIG PEIRRAISGD LTAEEELDKA MKEAVSAASE
  1741  DDIFRRAGGL FGNHVSYYQS DGRSAFPQTF TTQRPLHINK AGSSQGDTES PSHEKLVDST
  1801  FTPSSYSSTG SNANINNANN TALGRLPRPA GYPSTVSTVE GHGPPLSPAI RVQEVAWKLS
  1861  SNRERHVPMC EDLELRRDSG SAGTQAHCLL LRKANPSRCH SRESQAAMAG QEETSQDETY
  1921  EVKMNHDTEA CSEPSLLSTE MLSYQDDENR QLTLPEEDKR DIRQSPKRGF LRSASLGRRA
  1981  SFHLECLKRQ KDRGGDISQK TVLPLHLVHH QALAVAGLSP LLQRSHSPAS FPRPFATPPA
  2041  TPGSRGWPPQ PVPTLRLEGV ESSEKLNSSF PSIHCGSWAE TTPGGGGSSA ARRVRPVSLM
  2101  VPSQAGAPGR QFHGSASSLV EAVLISEGLG QFAQDPKFIE VTTQELADAC DMTIEEMESA
  2161  ADNILSGGAP QSPNGALLPF VNCRDAGQDR AGGEEDAGCV RARGRPSEEE LQDSRVYVSS
  2221  L

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CACNA1C 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): 0.41
Highest tissue expression: 25 nTPM

Expression across tissuesHPA

Tissue

colon: 25 nTPM
endometrium: 16 nTPM
heart muscle: 15 nTPM
blood vessel: 14 nTPM
smooth muscle: 11 nTPM
urinary bladder: 9.4 nTPM

Single-cell type

brain inhibitory neurons: 712 nCPM
brain excitatory neurons: 661 nCPM
other brain neurons: 505 nCPM
vascular smooth muscle cells: 464 nCPM
oligodendrocyte progenitor cells: 284 nCPM
pericytes: 221 nCPM

Immune cell

basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM
MAIT T-cell: 0 nTPM

Brain region

cerebral cortex: 50 nTPM
amygdala: 45 nTPM
thalamus: 41 nTPM
basal ganglia: 40 nTPM
white matter: 37 nTPM
hippocampal formation: 35 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CACNA1C.

Disease | AllUniProt

Conditions CACNA1C is implicated in, by any mechanism.

Timothy syndrome (TS) MIM:601005
Brugada syndrome 3 (BRGDA3) MIM:611875
Long QT syndrome 8 (LQT8) MIM:618447
Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures (NEDHLSS) MIM:620029

Disease | GeneticClinVar

99 pathogenic / likely-pathogenic of 3,711 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Timothy syndrome
Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures
Cardiovascular phenotype
Long QT syndrome
Long QT syndrome 8

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): 0.1
gnomAD pLI: 1
gnomAD missense Z: 6.47
DepMap mean gene effect: -0.02
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 CACNA1C 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 CACNA1C as an antibody target. Whether an autoantibody or antibody against CACNA1C could matter depends on whether native CACNA1C is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CACNA1C is annotated at the cell surface, where native CACNA1C 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 CACNA1C as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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