Seroatlas · Human Serome Atlas

CACNA2D2

Voltage-dependent calcium channel subunit alpha-2/delta-2

Also known as: alpha2delta-2, CA2D2_HUMAN, KIAA0558

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

Protein identityUniProt · HPA

UniProt accession: Q9NY47
Gene: CACNA2D2
Ensembl: ENSG00000007402
Chromosome: 3
Canonical length: 1150 aa
Protein class: Disease related genes, FDA approved drug targets, Predicted intracellular proteins, Transporters
Subcellular location: Plasma membrane,Cytosol,Flagellar centriole,Mid piece

OverviewNCBI Gene

Calcium channels mediate the entry of calcium ions into the cell upon membrane polarization. This gene encodes the alpha-2/delta subunit of the voltage-dependent calcium channel complex. The complex consists of the main channel-forming subunit alpha-1, and auxiliary subunits alpha-2/delta, beta, and gamma. The auxiliary subunits function in the assembly and membrane localization of the complex, and modulate calcium currents and channel activation/inactivation kinetics. The subunit encoded by this gene undergoes post-translational cleavage to yield the extracellular alpha2 peptide and a membrane-anchored delta polypeptide. This subunit is a receptor for the antiepileptic drug, gabapentin. Mutations in this gene are associated with early infantile epileptic encephalopathy. Single nucleotide polymorphisms in this gene are correlated with increased sensitivity to opioid drugs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

Canonical amino-acid sequenceUniProt

1150 residues, UniProt reviewed canonical sequence.

>Q9NY47|CACNA2D2
     1  MAVPARTCGA SRPGPARTAR PWPGCGPHPG PGTRRPTSGP PRPLWLLLPL LPLLAAPGAS
    61  AYSFPQQHTM QHWARRLEQE VDGVMRIFGG VQQLREIYKD NRNLFEVQEN EPQKLVEKVA
   121  GDIESLLDRK VQALKRLADA AENFQKAHRW QDNIKEEDIV YYDAKADAEL DDPESEDVER
   181  GSKASTLRLD FIEDPNFKNK VNYSYAAVQI PTDIYKGSTV ILNELNWTEA LENVFMENRR
   241  QDPTLLWQVF GSATGVTRYY PATPWRAPKK IDLYDVRRRP WYIQGASSPK DMVIIVDVSG
   301  SVSGLTLKLM KTSVCEMLDT LSDDDYVNVA SFNEKAQPVS CFTHLVQANV RNKKVFKEAV
   361  QGMVAKGTTG YKAGFEYAFD QLQNSNITRA NCNKMIMMFT DGGEDRVQDV FEKYNWPNRT
   421  VRVFTFSVGQ HNYDVTPLQW MACANKGYYF EIPSIGAIRI NTQEYLDVLG RPMVLAGKEA
   481  KQVQWTNVYE DALGLGLVVT GTLPVFNLTQ DGPGEKKNQL ILGVMGIDVA LNDIKRLTPN
   541  YTLGANGYVF AIDLNGYVLL HPNLKPQTTN FREPVTLDFL DAELEDENKE EIRRSMIDGN
   601  KGHKQIRTLV KSLDERYIDE VTRNYTWVPI RSTNYSLGLV LPPYSTFYLQ ANLSDQILQV
   661  KLPISKLKDF EFLLPSSFES EGHVFIAPRE YCKDLNASDN NTEFLKNFIE LMEKVTPDSK
   721  QCNNFLLHNL ILDTGITQQL VERVWRDQDL NTYSLLAVFA ATDGGITRVF PNKAAEDWTE
   781  NPEPFNASFY RRSLDNHGYV FKPPHQDALL RPLELENDTV GILVSTAVEL SLGRRTLRPA
   841  VVGVKLDLEA WAEKFKVLAS NRTHQDQPQK CGPNSHCEMD CEVNNEDLLC VLIDDGGFLV
   901  LSNQNHQWDQ VGRFFSEVDA NLMLALYNNS FYTRKESYDY QAACAPQPPG NLGAAPRGVF
   961  VPTVADFLNL AWWTSAAAWS LFQQLLYGLI YHSWFQADPA EAEGSPETRE SSCVMKQTQY
  1021  YFGSVNASYN AIIDCGNCSR LFHAQRLTNT NLLFVVAEKP LCSQCEAGRL LQKETHSDGP
  1081  EQCELVQRPR YRRGPHICFD YNATEDTSDC GRGASFPPSL GVLVSLQLLL LLGLPPRPQP
  1141  QVLVHASRRL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CACNA2D2 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: 1
Mean surface accessibility (rSASA): 0.29
Highest tissue expression: 46 nTPM

Expression across tissuesHPA

Tissue

lung: 46 nTPM
cerebellum: 15 nTPM
hypothalamus: 8.1 nTPM
retina: 8 nTPM
heart muscle: 7.8 nTPM
pituitary gland: 6.5 nTPM

Single-cell type

alveolar cells type 2: 299 nCPM
retinal amacrine cells: 170 nCPM
oocytes: 111 nCPM
transitional alveolar cells: 96 nCPM
corticotrophs: 96 nCPM
alveolar cells type 1: 82 nCPM

Immune cell

naive CD4 T-cell: 1.2 nTPM
T-reg: 1.2 nTPM
MAIT T-cell: 0.9 nTPM
memory CD4 T-cell: 0.9 nTPM
NK-cell: 0.9 nTPM
gdT-cell: 0.7 nTPM

Brain region

pons: 42 nTPM
hypothalamus: 41 nTPM
cerebellum: 32 nTPM
medulla oblongata: 30 nTPM
midbrain: 30 nTPM
cerebral cortex: 27 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CACNA2D2.

Disease | AllUniProt

Conditions CACNA2D2 is implicated in, by any mechanism.

Cerebellar atrophy with seizures and variable developmental delay (CASVDD) MIM:618501

Disease | GeneticClinVar

80 pathogenic / likely-pathogenic of 1,305 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Early-infantile DEE
Cerebellar atrophy with seizures and variable developmental delay
Epileptic encephalopathy
Developmental and epileptic encephalopathy

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): 0.23
gnomAD pLI: 1
gnomAD missense Z: 3
DepMap mean gene effect: -0.12
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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 CACNA2D2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

STOML2

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CACNA2D2 as an antibody target. Whether an autoantibody or antibody against CACNA2D2 could matter depends on whether native CACNA2D2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CACNA2D2 is annotated at the cell surface, where native CACNA2D2 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 CACNA2D2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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