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CPNE6

gene
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Also known as N-copinecopine-6

Summary

CPNE6 (copine 6, HGNC:2319) is a protein-coding gene on chromosome 14q11.2, encoding Copine-6 (O95741). Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes.

This gene encodes a member of the copine family. Members of this family are calcium-dependent, phospholipid-binding proteins with C2 domains, two calcium- and phospholipid-binding domains. Through their domain structure and lipid binding capabilities, these proteins may play a role in membrane trafficking. This protein is thought to be brain-specific and has a domain structure of two N-terminal C2 domains and one von Willebrand factor A domain. It may have a role in synaptic plasticity.

Source: NCBI Gene 9362 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
  • GWAS associations: 1
  • Clinical variants (ClinVar): 57 total
  • MANE Select transcript: NM_006032

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:2319
Approved symbolCPNE6
Namecopine 6
Location14q11.2
Locus typegene with protein product
StatusApproved
AliasesN-copine, copine-6
Ensembl geneENSG00000100884
Ensembl biotypeprotein_coding
OMIM605688
Entrez9362

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000397016, ENST00000460657, ENST00000537691, ENST00000557829, ENST00000557889, ENST00000558450, ENST00000558541, ENST00000558795, ENST00000558859, ENST00000558995, ENST00000559197, ENST00000559207, ENST00000559778, ENST00000560092, ENST00000560356, ENST00000560761, ENST00000560828, ENST00000560845, ENST00000560884, ENST00000689861, ENST00000966862

RefSeq mRNA: 5 — MANE Select: NM_006032 NM_001280558, NM_001385056, NM_001385057, NM_001385058, NM_006032

CCDS: CCDS61413, CCDS9607

Canonical transcript exons

ENST00000647071 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 97.08.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.2311 / max 265.6186, expressed in 148 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
1389703.4543132
1389690.483483
1389670.164559
1389680.114857
1389710.01419

Top tissues by expression

131 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
temporal lobeUBERON:000187197.08gold quality
amygdalaUBERON:000187697.05gold quality
right hemisphere of cerebellumUBERON:001489096.37gold quality
Ammon’s hornUBERON:000195496.18gold quality
cerebellar hemisphereUBERON:000224596.10gold quality
cerebellar cortexUBERON:000212996.08gold quality
cerebellumUBERON:000203796.04gold quality
superior frontal gyrusUBERON:000266195.83gold quality
right frontal lobeUBERON:000281095.81gold quality
nucleus accumbensUBERON:000188295.51gold quality
frontal cortexUBERON:000187095.49gold quality
anterior cingulate cortexUBERON:000983595.36gold quality
prefrontal cortexUBERON:000045195.23gold quality
putamenUBERON:000187494.90gold quality
cerebral cortexUBERON:000095694.52gold quality
caudate nucleusUBERON:000187394.52gold quality
dorsolateral prefrontal cortexUBERON:000983494.42gold quality
Brodmann (1909) area 9UBERON:001354094.30gold quality
hypothalamusUBERON:000189893.23gold quality
brainUBERON:000095593.04gold quality
primary visual cortexUBERON:000243690.04gold quality
substantia nigraUBERON:000203889.89gold quality
C1 segment of cervical spinal cordUBERON:000646982.85gold quality
corpus callosumUBERON:000233681.75gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099181.40silver quality
pituitary glandUBERON:000000778.66gold quality
duodenumUBERON:000211478.37gold quality
adenohypophysisUBERON:000219677.85gold quality
cortical plateUBERON:000534377.80gold quality
adult mammalian kidneyUBERON:000008270.47gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-GEOD-84465yes10.67
E-ANND-3no1.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting CPNE6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-453199.9969.703181
HSA-MIR-7152-3P99.9767.47849
HSA-MIR-6809-3P99.9171.453814
HSA-MIR-4753-3P99.9071.033786
HSA-MIR-430699.7270.503630
HSA-MIR-6715B-5P99.6469.631420
HSA-MIR-613499.6365.681537
HSA-MIR-426999.5569.891373
HSA-MIR-1213199.4868.721673
HSA-MIR-608199.4866.071446
HSA-MIR-361299.4566.021333
HSA-MIR-65099.4565.771309
HSA-MIR-185-5P99.3568.602497
HSA-MIR-464499.3569.122514
HSA-MIR-485-5P99.1064.781889
HSA-MIR-6884-5P99.1064.501987
HSA-MIR-447899.0765.162320
HSA-MIR-5587-5P99.0768.58838
HSA-MIR-211798.4867.971307
HSA-MIR-6864-5P98.3866.591079
HSA-MIR-444398.0266.251928
HSA-MIR-193B-5P97.9165.88837
HSA-MIR-127096.9466.65931
HSA-MIR-62096.9466.79888
HSA-MIR-519296.8963.35879
HSA-MIR-6890-5P92.8965.83442

Literature-anchored findings (GeneRIF, showing 2)

  • expression of CPNE6 increased remarkably in brains of epileptic patients and in experimental epileptic rats. Expression is mainly in neurons. (PMID:26723968)
  • we identify copine-6 as a specific regulator of spontaneous neurotransmission (PMID:29802203)

Cross-species orthologs

8 orthologs

OrganismSymbolGene ID
danio_reriocpne8ENSDARG00000025189
danio_reriosi:cabz01087415.1ENSDARG00000115094
mus_musculusCpne6ENSMUSG00000022212
rattus_norvegicusCpne6ENSRNOG00000018399
caenorhabditis_elegansWBGENE00001577
caenorhabditis_elegansWBGENE00006441
caenorhabditis_elegansWBGENE00012128
caenorhabditis_elegansWBGENE00015061

Paralogs (8): CPNE3 (ENSG00000085719), CPNE5 (ENSG00000124772), CPNE8 (ENSG00000139117), CPNE2 (ENSG00000140848), CPNE9 (ENSG00000144550), CPNE7 (ENSG00000178773), CPNE4 (ENSG00000196353), CPNE1 (ENSG00000214078)

Protein

Protein identifiers

Copine-6 — O95741 (reviewed: O95741)

Alternative names: Copine VI, Neuronal-copine

All UniProt accessions (13): O95741, H0YK44, H0YKJ0, H0YKP1, H0YLM2, H0YLS9, H0YLV2, H0YM67, H0YNM7, H0YNP2, H0YNV2, H0YNV6, H0YNX4

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes. Binds phospholipid membranes in a calcium-dependent manner. Plays a role in dendrite formation by melanocytes.

Subunit / interactions. Interacts (via second C2 domain) with OS9 (via C-terminus); this interaction occurs in a calcium-dependent manner in vitro. May interact with NECAB1.

Subcellular location. Cytoplasm. Cell membrane. Endosome. Cytoplasmic vesicle. Clathrin-coated vesicle. Perikaryon. Cell projection. Dendrite.

Tissue specificity. Widely expressed in the brain. Expressed weakly in the kidney, liver and fetal heart. Expressed in melanocytes.

Domain organisation. The C2 domain 1 binds phospholipids in a calcium-independent manner and is not necessary for calcium-mediated translocation and association to the plasma membrane. The C2 domain 2 binds phospholipids in a calcium-dependent manner and is necessary for calcium-mediated translocation and association to the plasma membrane. The linker region contributes to the calcium-dependent translocation and association to the plasma membrane. The VWFA domain is necessary for association with intracellular clathrin-coated vesicles in a calcium-dependent manner.

Similarity. Belongs to the copine family.

Isoforms (2)

UniProt IDNamesCanonical?
O95741-11yes
O95741-22

RefSeq proteins (5): NP_001267487, NP_001371985, NP_001371986, NP_001371987, NP_006023* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000008C2_domDomain
IPR002035VWF_ADomain
IPR010734Copine_CDomain
IPR035892C2_domain_sfHomologous_superfamily
IPR036465vWFA_dom_sfHomologous_superfamily
IPR037768C2B_CopineDomain
IPR045052CopineFamily

Pfam: PF00168, PF07002

UniProt features (18 total): binding site 8, sequence conflict 4, domain 3, chain 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O95741-F186.850.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 231; 231; 237; 167; 167; 173; 229; 229

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-1483206Glycerophospholipid biosynthesis

MSigDB gene sets: 132 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, MODULE_274, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GGGTGGRR_PAX4_03, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_RESPONSE_TO_METAL_ION, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (5): cell differentiation (GO:0030154), glycerophospholipid biosynthetic process (GO:0046474), cellular response to calcium ion (GO:0071277), postsynaptic actin cytoskeleton organization (GO:0098974), positive regulation of dendrite extension (GO:1903861)

GO Molecular Function (6): phosphatidylserine binding (GO:0001786), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), calcium-dependent phospholipid binding (GO:0005544), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): endosome (GO:0005768), plasma membrane (GO:0005886), membrane (GO:0016020), axon (GO:0030424), dendrite (GO:0030425), perikaryon (GO:0043204), clathrin-coated endocytic vesicle (GO:0045334), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), clathrin-coated vesicle (GO:0030136), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Phospholipid metabolism1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
phospholipid binding2
neuron projection2
cellular developmental process1
glycerophospholipid metabolic process1
phospholipid biosynthetic process1
glycerolipid biosynthetic process1
response to calcium ion1
cellular response to metal ion1
actin cytoskeleton organization1
postsynaptic cytoskeleton organization1
positive regulation of cell growth1
positive regulation of developmental growth1
dendrite extension1
regulation of dendrite extension1
anion binding1
modified amino acid binding1
metal ion binding1
lipid binding1
binding1
cation binding1
endomembrane system1
cytoplasmic vesicle1
membrane1
cell periphery1
dendritic tree1
neuronal cell body1
clathrin-coated vesicle1
endocytic vesicle1
extracellular vesicle1
intracellular anatomical structure1
coated vesicle1
cytoplasm1
intracellular vesicle1

Protein interactions and networks

STRING

1668 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CPNE6AK5Q9Y6K8622
CPNE6OS9Q13438494
CPNE6SDR42E1Q8WUS8476
CPNE6TRIM46Q7Z4K8465
CPNE6NRXN3Q9Y4C0433
CPNE6CCDC8Q9H0W5428
CPNE6SRRM5B3KS81426
CPNE6ANKS1BQ7Z6G8423
CPNE6SYTL1Q8IYJ3418
CPNE6STK33Q9BYT3417
CPNE6CHADO15335404
CPNE6TIAM1Q13009398
CPNE6EGFLAMQ63HQ2398
CPNE6HAPLN2Q9GZV7397
CPNE6LIMK1P53667391

IntAct

22 interactions, top by confidence:

ABTypeScore
CPNE6MEOX2psi-mi:“MI:0915”(physical association)0.560
CPNE6ANXA6psi-mi:“MI:0915”(physical association)0.400
ECE1CPNE6psi-mi:“MI:0915”(physical association)0.370
CPNE6ANXA7psi-mi:“MI:0915”(physical association)0.370
CDKN1ACPNE6psi-mi:“MI:0915”(physical association)0.370
CPNE6GRB7psi-mi:“MI:0915”(physical association)0.370
MAPK11CPNE6psi-mi:“MI:0915”(physical association)0.370
CPNE6LAMTOR3psi-mi:“MI:0915”(physical association)0.370
PIN1CPNE6psi-mi:“MI:0915”(physical association)0.370
CPNE6SMN1psi-mi:“MI:0915”(physical association)0.370
CPNE6TK1psi-mi:“MI:0915”(physical association)0.370
TTRCPNE6psi-mi:“MI:0915”(physical association)0.370
CPNE4SUPT5Hpsi-mi:“MI:0914”(association)0.350
CSAG2CAMK2Dpsi-mi:“MI:0914”(association)0.350
ITM2BILVBLpsi-mi:“MI:0914”(association)0.350
CPNE4CPNE6psi-mi:“MI:0914”(association)0.350
AK5CPNE6psi-mi:“MI:0915”(physical association)0.000

BioGRID (18): CPNE6 (Two-hybrid), CPNE6 (Reconstituted Complex), CPNE6 (Affinity Capture-MS), CPNE6 (Affinity Capture-MS), AK5 (Two-hybrid), AGR2 (Two-hybrid), ANXA6 (Proximity Label-MS), CPNE6 (Affinity Capture-MS), CPNE6 (Affinity Capture-MS), CPNE6 (Two-hybrid), CPNE6 (Two-hybrid), CPNE6 (Two-hybrid), CPNE6 (Two-hybrid), CPNE6 (Two-hybrid), CPNE6 (Two-hybrid)

ESM2 similar proteins: A0JNU3, A6H791, A7YW45, D4A1R8, H1UBN0, O14744, O35654, O75131, O95741, P10688, P10895, P49004, P51178, P59108, Q02053, Q08DB4, Q0VE82, Q1RLL3, Q28HC6, Q2HB00, Q2KHY1, Q4QR99, Q4R5M3, Q5BJS7, Q5R4W6, Q5R698, Q5RAE1, Q5U300, Q64737, Q66JK4, Q6AY46, Q6NS21, Q7SYK1, Q86YQ8, Q8BLR2, Q8BT60, Q8C166, Q8CIG8, Q8IYJ1, Q8JZW4

Diamond homologs: A8WMY4, D4A1R8, H1UBN0, H2KYS8, O75131, O95741, P59108, Q08DB4, Q0VE82, Q1RLL3, Q1ZXB3, Q2KHY1, Q54FY7, Q54P51, Q55GG1, Q5BJS7, Q5R4W6, Q5RAE1, Q5S1W2, Q5XQC7, Q7YXU4, Q86K21, Q86YQ8, Q8BLR2, Q8BT60, Q8C166, Q8IYJ1, Q8JZW4, Q941L3, Q96A23, Q96FN4, Q99829, Q9DC53, Q9HCH3, Q9UBL6, Q9XUB9, Q9Z140, A0JJX5, Q09219, Q12466

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

57 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance52
Likely benign2
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2226 predictions. Top by Δscore:

VariantEffectΔscore
14:24072931:A:AGacceptor_gain1.0000
14:24072932:G:GGacceptor_gain1.0000
14:24073102:GAGG:Gdonor_loss1.0000
14:24073104:GGT:Gdonor_loss1.0000
14:24073105:G:Tdonor_loss1.0000
14:24074285:TTGCA:Tacceptor_loss1.0000
14:24074286:TGCA:Tacceptor_loss1.0000
14:24074287:GCAGA:Gacceptor_loss1.0000
14:24074288:CAG:Cacceptor_loss1.0000
14:24074289:A:AGacceptor_gain1.0000
14:24074289:AG:Aacceptor_loss1.0000
14:24074290:G:Aacceptor_loss1.0000
14:24074290:G:GAacceptor_gain1.0000
14:24074290:GATC:Gacceptor_gain1.0000
14:24074520:T:TAacceptor_gain1.0000
14:24074524:T:Gacceptor_gain1.0000
14:24074529:A:AGacceptor_gain1.0000
14:24074529:AG:Aacceptor_gain1.0000
14:24074530:G:GAacceptor_gain1.0000
14:24074530:GG:Gacceptor_gain1.0000
14:24074530:GGAT:Gacceptor_gain1.0000
14:24074530:GGATC:Gacceptor_gain1.0000
14:24074615:G:GAdonor_loss1.0000
14:24074703:AAGGT:Aacceptor_gain1.0000
14:24075170:A:AGacceptor_gain1.0000
14:24075171:G:GAacceptor_gain1.0000
14:24075241:G:GTdonor_gain1.0000
14:24075250:G:GTdonor_gain1.0000
14:24075251:A:Tdonor_gain1.0000
14:24075255:G:GTdonor_gain1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000745403 (14:24073981 T>C), RS1001345682 (14:24075760 C>A,T), RS1002165370 (14:24069859 T>A), RS1002280088 (14:24069620 A>G), RS1002851414 (14:24072570 G>A,C,T), RS1002882548 (14:24072401 G>A), RS1003041309 (14:24076764 A>C), RS1003055325 (14:24070102 TGGG>T), RS1003188278 (14:24071308 G>A,T), RS1003284693 (14:24071070 G>A), RS1003374166 (14:24075217 G>A), RS1003394793 (14:24070465 C>T), RS1004465497 (14:24071073 C>A,G), RS1004899237 (14:24070804 A>G,T), RS1005142255 (14:24078288 G>T)

Disease associations

OMIM: gene MIM:605688 | disease phenotypes:

GenCC curated gene-disease

DiseaseClassificationInheritance
complex neurodevelopmental disorderLimitedAutosomal recessive

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

StudyTraitp-value
GCST010244_350Triglyceride levels4.000000e-08

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0004530triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyreneaffects methylation, decreases expression, increases mutagenesis3
Aflatoxin B1decreases expression2
methyleugenoldecreases expression1
sodium arseniteincreases expression1
4-aminophenylarsenoxideaffects binding, decreases reaction1
CGP 52608affects binding, increases reaction1
bisphenol Sdecreases expression1
Arsenic Trioxidedecreases reaction, affects binding1
Cyclosporinedecreases methylation1
Okadaic Aciddecreases expression1

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT06310681Not specifiedCOMPLETEDPilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049Not specifiedNOT_YET_RECRUITINGCognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot