CPNE2

Summary

CPNE2 (copine 2, HGNC:2315) is a protein-coding gene on chromosome 16q13, encoding Copine-2 (Q96FN4). Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes.

Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene is one of several genes that encode a calcium-dependent protein containing two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. Sequence analysis identified multiple alternatively spliced transcript variants but their full-length natures could not be determined.

Source: NCBI Gene 221184 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_152727

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2315
Approved symbol	CPNE2
Name	copine 2
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	CPN2
Ensembl gene	ENSG00000140848
Ensembl biotype	protein_coding
OMIM	604206
Entrez	221184

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 23 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000290776, ENST00000535318, ENST00000565766, ENST00000565874, ENST00000565951, ENST00000566042, ENST00000566259, ENST00000566910, ENST00000567011, ENST00000567487, ENST00000882839, ENST00000882840, ENST00000882841, ENST00000882842, ENST00000882843, ENST00000882844, ENST00000882845, ENST00000882846, ENST00000930207, ENST00000930208, ENST00000930209, ENST00000930210, ENST00000930211, ENST00000940961, ENST00000940962, ENST00000940963, ENST00000940964

RefSeq mRNA: 1 — MANE Select: NM_152727 NM_152727

CCDS: CCDS10774

Canonical transcript exons

ENST00000290776 — 16 exons

Exon	Start	End
ENSE00000945298	57115476	57115550
ENSE00000945299	57117496	57117567
ENSE00000945300	57119195	57119278
ENSE00000945301	57119561	57119650
ENSE00000945303	57121674	57121760
ENSE00001046421	57121093	57121191
ENSE00001046456	57123414	57123473
ENSE00002595237	57092583	57092790
ENSE00003459828	57134775	57134826
ENSE00003524414	57137149	57137282
ENSE00003529639	57147551	57148369
ENSE00003534962	57110708	57110922
ENSE00003566187	57127849	57127903
ENSE00003592448	57125860	57125993
ENSE00003650415	57146085	57146321
ENSE00003659783	57113288	57113467

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 97.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.6516 / max 1011.4871, expressed in 1743 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154309	11.8708	1722
154308	0.7431	473
154307	0.6274	387
154314	0.1530	40
154312	0.0881	37
154310	0.0877	27
154311	0.0815	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.22	gold quality
ventricular zone	UBERON:0003053	97.12	gold quality
spinal cord	UBERON:0002240	96.85	gold quality
ileal mucosa	UBERON:0000331	96.36	gold quality
inferior vagus X ganglion	UBERON:0005363	95.86	gold quality
hypothalamus	UBERON:0001898	95.85	gold quality
mucosa of transverse colon	UBERON:0004991	95.40	gold quality
right lung	UBERON:0002167	94.39	gold quality
ganglionic eminence	UBERON:0004023	94.10	gold quality
embryo	UBERON:0000922	94.09	gold quality
amygdala	UBERON:0001876	94.08	gold quality
substantia nigra	UBERON:0002038	94.04	gold quality
midbrain	UBERON:0001891	93.83	gold quality
Ammon’s horn	UBERON:0001954	93.78	gold quality
corpus callosum	UBERON:0002336	93.76	gold quality
upper lobe of left lung	UBERON:0008952	93.66	gold quality
transverse colon	UBERON:0001157	93.63	gold quality
peripheral nervous system	UBERON:0000010	93.62	gold quality
tibial nerve	UBERON:0001323	93.62	gold quality
omental fat pad	UBERON:0010414	93.51	gold quality
peritoneum	UBERON:0002358	93.47	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.43	gold quality
upper lobe of lung	UBERON:0008948	93.40	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.39	gold quality
right uterine tube	UBERON:0001302	93.35	gold quality
adipose tissue	UBERON:0001013	93.18	gold quality
lower esophagus mucosa	UBERON:0035834	93.12	gold quality
right coronary artery	UBERON:0001625	92.91	gold quality
nucleus accumbens	UBERON:0001882	92.83	gold quality
endocervix	UBERON:0000458	92.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8271	yes	14.79
E-ANND-3	yes	7.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting CPNE2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107

Literature-anchored findings (GeneRIF, showing 1)

• This protein has been found differentially expressed in the anterior cingulate cortex in women patients with schizophrenia. (PMID:20381070)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpne2	ENSDARG00000007753
mus_musculus	Cpne2	ENSMUSG00000034361
rattus_norvegicus	Cpne2	ENSRNOG00000043286
caenorhabditis_elegans		WBGENE00006441
caenorhabditis_elegans		WBGENE00015061

Paralogs (8): CPNE3 (ENSG00000085719), CPNE6 (ENSG00000100884), CPNE5 (ENSG00000124772), CPNE8 (ENSG00000139117), CPNE9 (ENSG00000144550), CPNE7 (ENSG00000178773), CPNE4 (ENSG00000196353), CPNE1 (ENSG00000214078)

Protein

Protein identifiers

Copine-2 — Q96FN4 (reviewed: Q96FN4)

Alternative names: Copine II

All UniProt accessions (4): Q96FN4, H3BPR8, H3BQQ3, H3BUC8

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes. Exhibits calcium-dependent cell membrane binding properties.

Subcellular location. Cytoplasm. Nucleus. Cell membrane.

Tissue specificity. Expressed in the brain. Expressed in neutrophil precursors from the bone marrow and peripheral blood.

Cofactor. Binds 3 Ca(2+) ions per C2 domain.

Domain organisation. The C2 domain 2, but not the C2 domain 1, is necessary for calcium-mediated membrane association. The linker region is necessary for calcium-dependent cell membrane association.

Similarity. Belongs to the copine family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96FN4-1	1	yes
Q96FN4-2	2

RefSeq proteins (1): NP_689940* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR002035	VWF_A	Domain
IPR010734	Copine_C	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR037768	C2B_Copine	Domain
IPR045052	Copine	Family

Pfam: PF00168, PF07002

UniProt features (26 total): binding site 19, domain 3, chain 1, splice variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FN4-F1	91.76	0.83

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 (19): 99; 99; 99; 102; 109; 109; 170; 170; 176; 232; 232; 234 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_GSTM1, GNF2_HPN, TACAATC_MIR508, GOBP_RESPONSE_TO_METAL_ION, GOBP_PROTEIN_STABILIZATION, GNF2_LCAT, HSIAO_LIVER_SPECIFIC_GENES, GOBP_REGULATION_OF_PROTEIN_STABILITY, GNF2_HPX, MODULE_88, GOBP_CELLULAR_RESPONSE_TO_CALCIUM_ION, MODULE_544, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, CTTTGTA_MIR524

GO Biological Process (1): cellular response to calcium ion (GO:0071277)

GO Molecular Function (3): calcium-dependent phospholipid binding (GO:0005544), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
response to calcium ion	1
cellular response to metal ion	1
phospholipid binding	1
cation binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPNE2	PSME3IP1	Q9GZU8	541
CPNE2	PRKRIP1	Q9H875	521
CPNE2	CMTR2	Q8IYT2	483
CPNE2	COG4	Q9H9E3	453
CPNE2	RAD1	O60671	445
CPNE2	CHCHD1	Q96BP2	419
CPNE2	CCDC167	Q9P0B6	375
CPNE2	FAM43B	Q6ZT52	366
CPNE2	DHX33	Q9H6R0	364
CPNE2	MOB3C	Q70IA8	363
CPNE2	AGAP4	Q96P64	354
CPNE2	SDSL	Q96GA7	353
CPNE2	LINC03041	A6NGG3	351
CPNE2	SLC22A16	Q86VW1	345
CPNE2	GNA15	P30679	332

IntAct

109 interactions, top by confidence:

A	B	Type	Score
SORBS3	CPNE2	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	CPNE2	psi-mi:“MI:0915”(physical association)	0.720
CPNE2	UBA3	psi-mi:“MI:0915”(physical association)	0.720
CPNE2	SORBS3	psi-mi:“MI:0915”(physical association)	0.720
UBA3	CPNE2	psi-mi:“MI:0915”(physical association)	0.720
CPNE2	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
THAP4	CPNE2	psi-mi:“MI:0915”(physical association)	0.670
ANAPC13	CDC27	psi-mi:“MI:0914”(association)	0.640
REL	CPNE2	psi-mi:“MI:0915”(physical association)	0.560
LNX1	CPNE2	psi-mi:“MI:0915”(physical association)	0.560
CPNE2	REL	psi-mi:“MI:0915”(physical association)	0.560
CPNE2	LNX1	psi-mi:“MI:0915”(physical association)	0.560
CPNE2	MEI4	psi-mi:“MI:0915”(physical association)	0.560
CPNE2	GBP7	psi-mi:“MI:0915”(physical association)	0.560
CPNE2	KATNBL1	psi-mi:“MI:0915”(physical association)	0.560
TCF4	CPNE2	psi-mi:“MI:0915”(physical association)	0.560
EFHC2	CPNE2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	CPNE2	psi-mi:“MI:0915”(physical association)	0.560
CPNE2	NCKIPSD	psi-mi:“MI:0915”(physical association)	0.560
CT55	CPNE2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (145): CPNE2 (Two-hybrid), CPNE2 (Two-hybrid), CPNE2 (Two-hybrid), CPNE2 (Two-hybrid), CPNE2 (Two-hybrid), CPNE2 (Affinity Capture-MS), CPNE2 (Co-fractionation), Pdcd6 (Two-hybrid), TRIM27 (Two-hybrid), CPNE2 (Affinity Capture-MS), CPNE2 (Affinity Capture-MS), CPNE2 (Affinity Capture-MS), CPNE2 (Affinity Capture-MS), HIP1 (Affinity Capture-MS), RABEP2 (Affinity Capture-MS)

ESM2 similar proteins: A0JJX5, A2WWV5, A2X479, B6ETT4, B8XCH5, O49303, O49435, O64492, O65554, P59108, Q0JBH9, Q0JHU5, Q0VE82, Q1RLL3, Q25AG5, Q5BJS7, Q6YWF1, Q7XA06, Q84TJ7, Q86YQ8, Q8BLR2, Q8IYJ1, Q8L706, Q8LFN9, Q8RXU9, Q944C1, Q96A23, Q96FN4, Q9C6B7, Q9C8S6, Q9C8Y2, Q9DC53, Q9FHP6, Q9FI32, Q9FIK8, Q9FJG3, Q9FL59, Q9FVJ3, Q9LP65, Q9LVH4

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3670 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57110706:A:AG	acceptor_gain	1.0000
16:57110707:G:GG	acceptor_gain	1.0000
16:57110920:GAGG:G	donor_loss	1.0000
16:57110922:GGT:G	donor_loss	1.0000
16:57110923:G:GC	donor_loss	1.0000
16:57110924:T:G	donor_loss	1.0000
16:57113274:T:A	acceptor_gain	1.0000
16:57113282:T:A	acceptor_gain	1.0000
16:57113286:A:AG	acceptor_gain	1.0000
16:57113287:G:GG	acceptor_gain	1.0000
16:57113287:GT:G	acceptor_gain	1.0000
16:57113287:GTAC:G	acceptor_gain	1.0000
16:57113412:G:GG	donor_gain	1.0000
16:57113463:GCACG:G	donor_gain	1.0000
16:57113468:G:GG	donor_gain	1.0000
16:57113468:GTGAG:G	donor_loss	1.0000
16:57115471:CCTA:C	acceptor_loss	1.0000
16:57115472:CTA:C	acceptor_loss	1.0000
16:57115473:TA:T	acceptor_loss	1.0000
16:57115474:A:AG	acceptor_gain	1.0000
16:57115474:A:C	acceptor_loss	1.0000
16:57115475:G:GG	acceptor_gain	1.0000
16:57115475:GA:G	acceptor_gain	1.0000
16:57115475:GAT:G	acceptor_gain	1.0000
16:57115475:GATC:G	acceptor_gain	1.0000
16:57117564:GAAG:G	donor_gain	1.0000
16:57117565:AAGG:A	donor_loss	1.0000
16:57117566:AGG:A	donor_loss	1.0000
16:57117568:GTAAG:G	donor_loss	1.0000
16:57117569:T:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000045987 (16:57137061 C>G,T), RS1000052790 (16:57096164 T>C,G), RS1000108318 (16:57130806 G>A), RS1000140294 (16:57122349 C>G,T), RS1000222627 (16:57131038 G>A), RS1000288976 (16:57124694 G>C,T), RS1000422260 (16:57118601 G>A), RS1000630052 (16:57113011 C>T), RS1000713984 (16:57141421 G>C), RS1000780344 (16:57106600 C>A), RS1000831906 (16:57141705 T>C), RS1001115307 (16:57129425 A>G), RS1001213997 (16:57148345 A>C), RS1001303026 (16:57115664 C>A,G,T), RS1001377593 (16:57144382 G>A)

Disease associations

OMIM: gene MIM:604206 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, decreases expression, increases abundance	4
trichostatin A	affects cotreatment, decreases expression	3
Smoke	increases abundance, increases expression, decreases expression	3
Acetaminophen	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, decreases expression, increases methylation	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects methylation, increases methylation	2
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
lead acetate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
corosolic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
belinostat	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1

Clinical trials (associated diseases)

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