Seroatlas · Human Serome Atlas

CACNA1D

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

Also known as: CAC1D_HUMAN, CACH3, CACN4, CACNL1A2, Cav1.3, CCHL1A2

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

Protein identityUniProt · HPA

UniProt accession: Q01668
Gene: CACNA1D
Ensembl: ENSG00000157388
Chromosome: 3
Canonical length: 2161 aa
Protein class: Cancer-related genes, 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: Nuclear membrane

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, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

Canonical amino-acid sequenceUniProt

2161 residues, UniProt reviewed canonical sequence.

>Q01668|CACNA1D
     1  MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
    61  RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
   121  SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
   181  IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
   241  AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
   301  CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
   361  ITMEGWTDVL YWMNDAMGFE LPWVYFVSLV IFGSFFVLNL VLGVLSGEFS KEREKAKARG
   421  DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
   481  GEGENRGCCG SLCQAISKSK LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI
   541  SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT
   601  ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSMKSI ASLLLLLFLF
   661  IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ ILTGEDWNAV MYDGIMAYGG
   721  PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES LNTAQKEEAE EKERKKIARK
   781  ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP
   841  AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS
   901  AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF CRNYFNLLDM
   961  LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG LKHVVQCVFV AIRTIGNIMI
  1021  VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI LYKDGDVDSP VVRERIWQNS
  1081  DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA
  1141  FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY
  1201  VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV EMVLKVIAFK
  1261  PKGYFSDAWN TFDSLIVIGS IIDVALSEAD PTESENVPVP TATPGNSEES NRISITFFRL
  1321  FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML FFIYAVIGMQ MFGKVAMRDN
  1381  NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL CDPESDYNPG EEYTCGSNFA
  1441  IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH HLDEFKRIWS EYDPEAKGRI
  1501  KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS DGTVMFNATL FALVRTALKI
  1561  KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE VTVGKFYATF LIQDYFRKFK
  1621  KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC DLQDDEPEET KREEEDDVFK
  1681  RNGALLGNHV NHVNSDRRDS LQQTNTTHRP LHVQRPSIPP ASDTEKPLFP PAGNSVCHNH
  1741  HNHNSIGKQV PTSTNANLNN ANMSKAAHGK RPSIGNLEHV SENGHHSSHK HDREPQRRSS
  1801  VKRTRYYETY IRSDSGDEQL PTICREDPEI HGYFRDPHCL GEQEYFSSEE CYEDDSSPTW
  1861  SRQNYGYYSR YPGRNIDSER PRGYHHPQGF LEDDDSPVCY DSRRSPRRRL LPPTPASHRR
  1921  SSFNFECLRR QSSQEEVPSS PIFPHRTALP LHLMQQQIMA VAGLDSSKAQ KYSPSHSTRS
  1981  WATPPATPPY RDWTPCYTPL IQVEQSEALD QVNGSLPSLH RSSWYTDEPD ISYRTFTPAS
  2041  LTVPSSFRNK NSDKQRSADS LVEAVLISEG LGRYARDPKF VSATKHEIAD ACDLTIDEME
  2101  SAASTLLNGN VRPRANGDVG PLSHRQDYEL QDFGPGYSDE EPDPGRDEED LADEMICITT
  2161  L

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CACNA1D 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): 0.4
Highest tissue expression: 7.1 nTPM

Expression across tissuesHPA

Tissue

fallopian tube: 7.1 nTPM
epididymis: 6.6 nTPM
adrenal gland: 6 nTPM
cervix: 5.5 nTPM
retina: 3.9 nTPM
pituitary gland: 3.6 nTPM

Single-cell type

thyrotrophs: 1,007 nCPM
adrenal cortex cells: 859 nCPM
retinal amacrine cells: 727 nCPM
retinal pigment epithelial cells: 716 nCPM
corticotrophs: 671 nCPM
somatotrophs: 602 nCPM

Immune cell

basophil: 3.7 nTPM
eosinophil: 0.3 nTPM
myeloid DC: 0.1 nTPM
neutrophil: 0.1 nTPM
classical monocyte: 0 nTPM
gdT-cell: 0 nTPM

Brain region

cerebral cortex: 55 nTPM
amygdala: 48 nTPM
white matter: 47 nTPM
thalamus: 41 nTPM
basal ganglia: 40 nTPM
cerebellum: 39 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CACNA1D.

Disease | AllUniProt

Conditions CACNA1D is implicated in, by any mechanism.

Sinoatrial node dysfunction and deafness (SANDD) MIM:614896
Primary aldosteronism, seizures, and neurologic abnormalities (PASNA) MIM:615474

Disease | GeneticClinVar

22 pathogenic / likely-pathogenic of 2,654 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Sinoatrial node dysfunction and deafness
Aldosterone-producing adenoma with seizures and neurological abnormalities
Inborn genetic diseases
See cases
Congenital disorder of glycosylation, type Iw, autosomal dominant

Disease | ImmuneIEDB

Conditions an epitope on CACNA1D was assayed in.

type 1 diabetes mellitus B cell

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): 0.21
gnomAD pLI: 1
gnomAD missense Z: 4.58
DepMap mean gene effect: 0
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 CACNA1D 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 CACNA1D as an antibody target. Whether an autoantibody or antibody against CACNA1D could matter depends on whether native CACNA1D is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CACNA1D is annotated at the cell surface, where native CACNA1D 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 CACNA1D as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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