CPNE9

Summary

CPNE9 (copine family member 9, HGNC:24336) is a protein-coding gene on chromosome 3p25.3, encoding Copine-9 (Q8IYJ1). Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes.

Predicted to enable calcium-dependent phospholipid binding activity. Involved in positive regulation of dendrite extension. Located in extracellular exosome.

Source: NCBI Gene 151835 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_153635

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24336
Approved symbol	CPNE9
Name	copine family member 9
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA4217
Ensembl gene	ENSG00000144550
Ensembl biotype	protein_coding
Entrez	151835

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000273027, ENST00000383831, ENST00000383832, ENST00000491802, ENST00000942639, ENST00000942640

RefSeq mRNA: 2 — MANE Select: NM_153635 NM_001308388, NM_153635

CCDS: CCDS2574, CCDS77695

Canonical transcript exons

ENST00000383832 — 21 exons

Exon	Start	End
ENSE00000965701	9717058	9717104
ENSE00000965705	9726665	9726722
ENSE00001165261	9727113	9727186
ENSE00001165287	9715974	9716035
ENSE00001165298	9715289	9715364
ENSE00001165305	9712975	9713079
ENSE00001214513	9704587	9704627
ENSE00001214594	9714914	9714955
ENSE00001214620	9712541	9712604
ENSE00001214643	9704749	9704795
ENSE00001289640	9718029	9718210
ENSE00001295688	9725949	9726051
ENSE00001302173	9718475	9718602
ENSE00001314874	9705987	9706063
ENSE00001324577	9705464	9705500
ENSE00001597806	9704891	9704994
ENSE00001611653	9705718	9705720
ENSE00001799588	9712725	9712828
ENSE00001929610	9703833	9704064
ENSE00001942755	9729507	9729908
ENSE00003625279	9715473	9715526

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 94.91.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9136 / max 121.6298, expressed in 101 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35220	0.8181	101
35219	0.0955	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	94.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.44	gold quality
pancreatic ductal cell	CL:0002079	93.42	gold quality
cerebellar hemisphere	UBERON:0002245	92.85	gold quality
cerebellar cortex	UBERON:0002129	92.78	gold quality
pons	UBERON:0000988	92.65	gold quality
cerebellum	UBERON:0002037	91.97	gold quality
oocyte	CL:0000023	90.71	gold quality
right frontal lobe	UBERON:0002810	90.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.77	gold quality
prefrontal cortex	UBERON:0000451	87.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.97	gold quality
frontal cortex	UBERON:0001870	85.93	gold quality
secondary oocyte	CL:0000655	84.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.73	gold quality
neocortex	UBERON:0001950	83.67	gold quality
cerebellar vermis	UBERON:0004720	83.17	gold quality
primary visual cortex	UBERON:0002436	82.61	gold quality
anterior cingulate cortex	UBERON:0009835	82.50	gold quality
occipital lobe	UBERON:0002021	80.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.76	silver quality
cerebral cortex	UBERON:0000956	79.36	gold quality
superior frontal gyrus	UBERON:0002661	77.94	gold quality
hypothalamus	UBERON:0001898	77.90	gold quality
postcentral gyrus	UBERON:0002581	77.07	gold quality
parietal lobe	UBERON:0001872	76.69	gold quality
brain	UBERON:0000955	75.82	gold quality
adenohypophysis	UBERON:0002196	74.68	gold quality
middle temporal gyrus	UBERON:0002771	74.25	gold quality
forebrain	UBERON:0001890	74.24	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.39

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• High expression of CPNE5 and CPNE9 predicts positive prognosis in multiple myeloma. (PMID:33780365)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpne9	ENSDARG00000098252
mus_musculus	Cpne9	ENSMUSG00000030270
rattus_norvegicus	Cpne9	ENSRNOG00000023077
caenorhabditis_elegans		WBGENE00001577
caenorhabditis_elegans		WBGENE00006441
caenorhabditis_elegans		WBGENE00012128
caenorhabditis_elegans		WBGENE00015061

Paralogs (8): CPNE3 (ENSG00000085719), CPNE6 (ENSG00000100884), CPNE5 (ENSG00000124772), CPNE8 (ENSG00000139117), CPNE2 (ENSG00000140848), CPNE7 (ENSG00000178773), CPNE4 (ENSG00000196353), CPNE1 (ENSG00000214078)

Protein

Protein identifiers

Copine-9 — Q8IYJ1 (reviewed: Q8IYJ1)

Alternative names: Copine IX

All UniProt accessions (2): Q8IYJ1, H7BXI0

UniProt curated annotations — full annotation on UniProt →

Function. Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes. Plays a role in dendrite formation by melanocytes.

Tissue specificity. Expressed in melanocytes.

Similarity. Belongs to the copine family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IYJ1-1	1	yes
Q8IYJ1-2	2

RefSeq proteins (2): NP_001295317, NP_705899* (*=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 (17 total): binding site 8, domain 3, chain 1, glycosylation site 1, splice variant 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYJ1-F1	90.15	0.73

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): 225; 227; 227; 233; 163; 163; 169; 225

Glycosylation sites (1): 95

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, LFA1_Q6, GOBP_GROWTH, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, GOBP_RESPONSE_TO_METAL_ION, GOBP_POSITIVE_REGULATION_OF_CELL_GROWTH, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_POSITIVE_REGULATION_OF_GROWTH, AACTTT_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_CALCIUM_ION, GOBP_DEVELOPMENTAL_CELL_GROWTH, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (3): cell differentiation (GO:0030154), cellular response to calcium ion (GO:0071277), positive regulation of dendrite extension (GO:1903861)

GO Molecular Function (2): calcium-dependent phospholipid binding (GO:0005544), metal ion binding (GO:0046872)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular developmental process	1
response to calcium ion	1
cellular response to metal ion	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
dendrite extension	1
regulation of dendrite extension	1
phospholipid binding	1
cation binding	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

940 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPNE9	LRRC40	Q9H9A6	443
CPNE9	FANCD2OS	Q96PS1	433
CPNE9	DZANK1	Q9NVP4	421
CPNE9	VWC2	Q2TAL6	410
CPNE9	ZCCHC18	P0CG32	405
CPNE9	RNFT2	Q96EX2	398
CPNE9	PRRT3	Q5FWE3	395
CPNE9	NHLH1	Q02575	375
CPNE9	LRRC24	Q50LG9	374
CPNE9	BRPF1	P55201	370
CPNE9	LONRF2	Q1L5Z9	364
CPNE9	TATDN2	Q93075	360
CPNE9	THUMPD3	Q9BV44	348
CPNE9	SSUH2	Q9Y2M2	348
CPNE9	SPINK8	P0C7L1	341

IntAct

8 interactions, top by confidence:

A	B	Type	Score
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
PRPH2	TOR1A	psi-mi:“MI:0914”(association)	0.350
CPNE9	RAD21	psi-mi:“MI:0914”(association)	0.350
CPNE9	GTPBP1	psi-mi:“MI:0914”(association)	0.350
SOHLH1	FANCA	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): CPNE9 (Affinity Capture-MS), CPNE9 (Affinity Capture-MS), CPNE9 (Affinity Capture-MS), RAD21 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), PTGES2 (Affinity Capture-MS), NPRL3 (Affinity Capture-MS), GET4 (Affinity Capture-MS), CPNE9 (Affinity Capture-MS), CPNE5 (Affinity Capture-MS), RIC8B (Affinity Capture-MS), FYN (Affinity Capture-MS), GTPBP1 (Affinity Capture-MS), MAP1S (Affinity Capture-MS), CPNE9 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2526 predictions. Top by Δscore:

Variant	Effect	Δscore
3:9704063:CGGT:C	donor_loss	1.0000
3:9704064:GGTG:G	donor_loss	1.0000
3:9704628:G:GG	donor_gain	1.0000
3:9704969:G:GT	donor_gain	1.0000
3:9704970:A:T	donor_gain	1.0000
3:9712821:G:GT	donor_gain	1.0000
3:9712825:GCAC:G	donor_gain	1.0000
3:9712829:G:GG	donor_gain	1.0000
3:9713101:G:GT	donor_gain	1.0000
3:9713101:G:T	donor_gain	1.0000
3:9715522:GAACT:G	donor_gain	1.0000
3:9715523:A:T	donor_gain	1.0000
3:9715524:ACT:A	donor_gain	1.0000
3:9715524:ACTG:A	donor_loss	1.0000
3:9715525:CT:C	donor_gain	1.0000
3:9715526:TG:T	donor_loss	1.0000
3:9715527:G:GG	donor_gain	1.0000
3:9715527:GTGA:G	donor_loss	1.0000
3:9718185:G:T	donor_gain	1.0000
3:9718603:GTA:G	donor_loss	1.0000
3:9718604:T:A	donor_loss	1.0000
3:9726050:GC:G	donor_gain	1.0000
3:9726052:G:GG	donor_gain	1.0000
3:9726063:G:GT	donor_gain	1.0000
3:9726721:GG:G	donor_gain	1.0000
3:9726722:GG:G	donor_gain	1.0000
3:9727111:A:AG	acceptor_gain	1.0000
3:9727112:G:GG	acceptor_gain	1.0000
3:9727112:GCA:G	acceptor_gain	1.0000
3:9727228:G:GG	donor_gain	1.0000

AlphaMissense

3639 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:9712792:C:A	P170H	1.000
3:9713027:T:A	W200R	1.000
3:9713027:T:C	W200R	1.000
3:9713028:G:C	W200S	1.000
3:9713029:G:C	W200C	1.000
3:9713029:G:T	W200C	1.000
3:9715302:G:C	G236R	1.000
3:9715303:G:A	G236D	1.000
3:9715303:G:T	G236V	1.000
3:9715522:G:A	G273E	1.000
3:9717087:A:C	D305A	1.000
3:9717087:A:T	D305V	1.000
3:9717088:C:A	D305E	1.000
3:9717088:C:G	D305E	1.000
3:9717103:T:A	N310K	1.000
3:9717103:T:G	N310K	1.000
3:9718158:G:A	G354D	1.000
3:9718160:T:C	F355L	1.000
3:9718162:T:A	F355L	1.000
3:9718162:T:G	F355L	1.000
3:9718164:G:A	G356E	1.000
3:9725990:T:C	L428P	1.000
3:9725993:T:C	L429P	1.000
3:9726002:C:T	T432I	1.000
3:9726005:A:T	D433V	1.000
3:9726007:G:A	G434R	1.000
3:9726007:G:C	G434R	1.000
3:9726007:G:T	G434W	1.000
3:9726008:G:A	G434E	1.000
3:9726008:G:T	G434V	1.000

dbSNP variants (sampled 300 via entrez): RS1000063463 (3:9705928 C>G,T), RS1000165686 (3:9709080 C>A,T), RS1000165889 (3:9721598 G>A), RS1000217798 (3:9709442 C>T), RS1000254766 (3:9728103 G>A), RS1000322801 (3:9721279 A>G), RS1000455617 (3:9726895 T>C), RS1000679434 (3:9728394 C>T), RS1000740567 (3:9727162 C>A), RS1000879334 (3:9709808 G>A), RS1000981182 (3:9715212 G>A), RS1001031409 (3:9722153 G>A,T), RS1001054667 (3:9722511 G>A), RS1001093516 (3:9716443 G>A), RS1001132841 (3:9727449 A>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003518_2	Daytime sleep phenotypes	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Clorgyline	increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Malathion	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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