CAMK2N1

Summary

CAMK2N1 (calcium/calmodulin dependent protein kinase II inhibitor 1, HGNC:24190) is a protein-coding gene on chromosome 1p36.12, encoding Calcium/calmodulin-dependent protein kinase II inhibitor 1 (Q7Z7J9). Potent and specific inhibitor of CaM-kinase II (CAMK2).

Predicted to enable calcium-dependent protein kinase inhibitor activity and protein kinase binding activity. Predicted to be involved in long-term memory and positive regulation of inflammatory response. Predicted to be located in neuronal cell body and synapse. Implicated in ovarian cancer; ovarian carcinoma; and prostate adenocarcinoma. Biomarker of hepatocellular carcinoma; oral squamous cell carcinoma; papillary thyroid carcinoma; and prostate cancer.

Source: NCBI Gene 55450 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 5 total — 1 pathogenic
• MANE Select transcript: NM_018584

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24190
Approved symbol	CAMK2N1
Name	calcium/calmodulin dependent protein kinase II inhibitor 1
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	CaMKIINalpha
Ensembl gene	ENSG00000162545
Ensembl biotype	protein_coding
OMIM	614986
Entrez	55450

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000375078, ENST00000489020, ENST00000941502

RefSeq mRNA: 1 — MANE Select: NM_018584 NM_018584

CCDS: CCDS207

Canonical transcript exons

ENST00000375078 — 2 exons

Exon	Start	End
ENSE00001465685	20482391	20483719
ENSE00001465686	20485214	20486210

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 127.5237 / max 9986.4442, expressed in 1550 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10750	107.0609	1538
10745	9.4999	1081
10746	4.9735	919
10748	4.3313	770
10747	0.9100	368
10744	0.4406	105
10743	0.3074	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 46	UBERON:0006483	99.79	gold quality
parietal lobe	UBERON:0001872	99.75	gold quality
postcentral gyrus	UBERON:0002581	99.75	gold quality
entorhinal cortex	UBERON:0002728	99.72	gold quality
orbitofrontal cortex	UBERON:0004167	99.70	gold quality
middle temporal gyrus	UBERON:0002771	99.67	gold quality
occipital lobe	UBERON:0002021	99.64	gold quality
medial globus pallidus	UBERON:0002477	99.63	gold quality
superior frontal gyrus	UBERON:0002661	99.62	gold quality
primary visual cortex	UBERON:0002436	99.61	gold quality
temporal lobe	UBERON:0001871	99.60	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.58	gold quality
amygdala	UBERON:0001876	99.53	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.53	gold quality
globus pallidus	UBERON:0001875	99.49	gold quality
CA1 field of hippocampus	UBERON:0003881	99.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.46	gold quality
prefrontal cortex	UBERON:0000451	99.45	gold quality
frontal cortex	UBERON:0001870	99.43	gold quality
cerebral cortex	UBERON:0000956	99.41	gold quality
Ammon’s horn	UBERON:0001954	99.40	gold quality
neocortex	UBERON:0001950	99.32	gold quality
right frontal lobe	UBERON:0002810	99.26	gold quality
telencephalon	UBERON:0001893	99.24	gold quality
cingulate cortex	UBERON:0003027	99.21	gold quality
anterior cingulate cortex	UBERON:0009835	99.21	gold quality
endothelial cell	CL:0000115	99.11	gold quality
lateral globus pallidus	UBERON:0002476	99.09	gold quality
ventral tegmental area	UBERON:0002691	99.06	gold quality
cerebellar vermis	UBERON:0004720	98.99	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-8559	yes	801.97
E-MTAB-7249	yes	461.37
E-MTAB-9154	yes	340.75
E-HCAD-35	yes	41.29
E-GEOD-135922	yes	32.96
E-GEOD-125970	yes	24.98
E-MTAB-10553	yes	20.76
E-GEOD-93593	yes	16.68
E-MTAB-5061	yes	14.78
E-CURD-114	yes	11.41
E-ANND-3	yes	11.22
E-GEOD-83139	yes	3.73
E-MTAB-7303	no	148.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, ZBTB17

miRNA regulators (miRDB)

113 targeting CAMK2N1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-96-5P	99.95	72.80	2140
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6809-3P	99.91	71.45	3814

Literature-anchored findings (GeneRIF, showing 11)

• Analyses suggest that CAMK2N1 plays a tumor suppressive role in prostate cancer cells. Reduced CAMK2N1 expression correlates to human prostate cancer progression and predicts poor clinical outcome. (PMID:25003983)
• contributes to prostate cancer growth and survival through androgen receptor-dependent signaling (PMID:25296973)
• Hypermethylation of RUNX3/CAMK2N1 is associated with poor clinical outcome in Type II EOC, also after macroscopic complete resection. (PMID:26175272)
• CAMK2N1 expression is significantly downregulated in human masticatory mucosa during wound healing (PMID:28005267)
• miR-532 promotes cell proliferation and invasion in t(4;14) MMs by targeting CAMK2N1. (PMID:31452083)
• MiR-129-5p promotes docetaxel resistance in prostate cancer by down-regulating CAMK2N1 expression. (PMID:31876385)
• Breakage of the oligomeric CaMKII hub by the regulatory segment of the kinase. (PMID:32902386)
• CAMK2N1 suppresses hepatoma growth through inhibiting E2F1-mediated cell-cycle signaling. (PMID:33068700)
• CAMK2N1 has a cancer-suppressive function in colorectal carcinoma via effects on the Wnt/beta-catenin pathway. (PMID:35998547)
• N6-methyladenosine-induced miR-182-5p promotes multiple myeloma tumorigenesis by regulating CAMK2N1. (PMID:38180718)
• Circ-IP6K2 suppresses tumor progression by modulating the miR-1292-5p/CAMK2N1 signal in clear cell renal cell carcinoma. (PMID:38980439)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	camk2n1	ENSDARG00000101387
mus_musculus	Camk2n1	ENSMUSG00000046447
rattus_norvegicus	Camk2n1	ENSRNOG00000090010

Paralogs (1): CAMK2N2 (ENSG00000163888)

Protein

Protein identifiers

Calcium/calmodulin-dependent protein kinase II inhibitor 1 — Q7Z7J9 (reviewed: Q7Z7J9)

Alternative names: CaMKII inhibitory protein alpha

All UniProt accessions (1): Q7Z7J9

UniProt curated annotations — full annotation on UniProt →

Function. Potent and specific inhibitor of CaM-kinase II (CAMK2). Plays a role in the maintenance of long-term retrieval-induced memory in response to contextual fear. Modulates blood pressure and vascular reactivity via regulation of CAMK2 activity in addition to regulation of left ventricular mass. Mediates the NLRP3 inflammasome in cardiomyocytes via acting as an inhibitor of the MAPK14/p38 and MAPK8/JNK pathways, thereby regulating ventricular remodeling and cardiac rhythm post-myocardial infarction. Negatively effects insulin sensitivity and promotes lipid formation in adipose tissues independent of CAMK2 signaling.

Subunit / interactions. Interacts with CAMK2B; the presence of Ca(2+)/calmodulin increases the interaction but is not essential. Interacts with CAMK2A; this interaction requires CAMK2A activation by Ca(2+).

Subcellular location. Synapse. Cell projection. Dendrite. Postsynaptic density.

Similarity. Belongs to the CAMK2N family.

RefSeq proteins (1): NP_061054* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026779	Camk2n	Family

Pfam: PF15170

UniProt features (2 total): chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7J9-F1	70.55	0.06

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 221 (showing top): GOBP_MEMORY, GNF2_RTN1, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, KOYAMA_SEMA3B_TARGETS_UP, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, AAAGACA_MIR511, GOBP_LONG_TERM_MEMORY, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, BASAKI_YBX1_TARGETS_DN

GO Biological Process (2): long-term memory (GO:0007616), positive regulation of inflammatory response (GO:0050729)

GO Molecular Function (3): calcium-dependent protein kinase inhibitor activity (GO:0008427), protein kinase binding (GO:0019901), protein kinase inhibitor activity (GO:0004860)

GO Cellular Component (4): postsynaptic density (GO:0014069), dendrite (GO:0030425), synapse (GO:0045202), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
memory	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
calcium-dependent protein serine/threonine kinase activity	1
calcium-dependent protein kinase regulator activity	1
protein serine/threonine kinase inhibitor activity	1
kinase binding	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
asymmetric synapse	1
postsynaptic specialization	1
neuron projection	1
dendritic tree	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAMK2N1	ARHGAP9	Q9BRR9	565
CAMK2N1	NRSN1	Q8IZ57	541
CAMK2N1	MAPK13	O15264	435
CAMK2N1	FAM43B	Q6ZT52	433
CAMK2N1	ANO7	Q6IWH7	418
CAMK2N1	ENAH	Q8N8S7	418
CAMK2N1	CACNG2	Q9Y698	413
CAMK2N1	IQGAP3	Q86VI3	413
CAMK2N1	MYBPC1	Q00872	410
CAMK2N1	BORA	Q6PGQ7	410
CAMK2N1	SCAMP5	Q8TAC9	409
CAMK2N1	SYT11	Q9BT88	409
CAMK2N1	DDX24	Q9GZR7	408
CAMK2N1	KCNH4	Q9UQ05	405
CAMK2N1	DLX1	P56177	402

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CAMK2G	PSMD12	psi-mi:“MI:0914”(association)	0.350
CAMK2D	OGT	psi-mi:“MI:0914”(association)	0.350
CAMK2A	OGT	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): CAMK2N1 (Affinity Capture-RNA), CAMK2N1 (Negative Genetic), CAMK2N1 (Affinity Capture-RNA), CAMK2N1 (Affinity Capture-MS), CAMK2N1 (Affinity Capture-MS), CAMK2N1 (Affinity Capture-MS), CAMK2N1 (Affinity Capture-MS), CAMK2N1 (Affinity Capture-MS), CAMK2N1 (Affinity Capture-MS), CAMK2N1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A023PXB0, A0A3G3C7T2, A5D7T0, A7MBG3, A9CBA1, B8J080, F5HES7, G2TRS6, O28696, O28885, O62694, O83952, P05339, P0A5G4, P0C5Q6, P11319, P21423, P23587, P23689, P38209, P40898, P41953, P55563, P64872, P65042, P65086, P87288, P9WKY2, P9WKY3, P9WL52, P9WL53, P9WLB2, P9WLB3, P9WLU8, P9WLU9, Q0IHT1, Q54D37, Q6GZN3, Q6P6Z4, Q6QWF9

Diamond homologs: A5D7T0, A7MBG3, Q0IHT1, Q6P6Z4, Q6QWF9, Q78WH7, Q7Z7J9, Q96S95, Q9JI15, Q9Z2N6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
59925	GRCh38/hg38 1p36.12(chr1:20482657-21271999)x1	Pathogenic

SpliceAI

257 predictions. Top by Δscore:

Variant	Effect	Δscore
1:20483717:CAA:C	acceptor_gain	1.0000
1:20483720:C:CC	acceptor_gain	1.0000
1:20485209:CTCA:C	donor_loss	0.9900
1:20485210:TCA:T	donor_loss	0.9900
1:20485211:CA:C	donor_loss	0.9900
1:20485212:ACC:A	donor_gain	0.9900
1:20485212:ACCCC:A	donor_loss	0.9900
1:20485213:C:CA	donor_loss	0.9900
1:20485213:CCC:C	donor_gain	0.9900
1:20485213:CCCCG:C	donor_gain	0.9900
1:20483716:ACAAC:A	acceptor_loss	0.9800
1:20483717:CAACT:C	acceptor_loss	0.9800
1:20483718:AA:A	acceptor_gain	0.9800
1:20483718:AACTG:A	acceptor_loss	0.9800
1:20483719:AC:A	acceptor_loss	0.9800
1:20483720:C:A	acceptor_loss	0.9800
1:20483721:T:G	acceptor_loss	0.9800
1:20485208:ACT:A	donor_loss	0.9800
1:20485212:A:AC	donor_gain	0.9800
1:20485212:AC:A	donor_gain	0.9800
1:20485213:C:CC	donor_gain	0.9800
1:20485213:CC:C	donor_gain	0.9800
1:20483715:AACAA:A	acceptor_gain	0.9700
1:20483716:ACAA:A	acceptor_gain	0.9700
1:20483717:CAAC:C	acceptor_gain	0.9700
1:20485207:AACT:A	donor_loss	0.9700
1:20484378:AG:A	donor_gain	0.9600
1:20484361:TCTTA:T	donor_loss	0.9400
1:20484362:CTTA:C	donor_loss	0.9400
1:20484363:TTACC:T	donor_loss	0.9400

AlphaMissense

511 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:20485228:C:T	G51D	1.000
1:20483707:T:A	D60V	0.999
1:20483708:C:G	D60H	0.999
1:20485228:C:A	G51V	0.999
1:20485229:C:G	G51R	0.999
1:20485231:A:C	I50S	0.999
1:20485231:A:T	I50N	0.999
1:20485240:A:T	L47Q	0.999
1:20485229:C:A	G51C	0.998
1:20485231:A:G	I50T	0.998
1:20485237:C:T	G48D	0.998
1:20485240:A:G	L47P	0.998
1:20485242:C:A	K46N	0.998
1:20485242:C:G	K46N	0.998
1:20485244:T:C	K46E	0.998
1:20483698:A:C	I63S	0.997
1:20483698:A:T	I63N	0.997
1:20483707:T:G	D60A	0.997
1:20483708:C:A	D60Y	0.997
1:20483713:A:T	I58N	0.997
1:20485226:G:A	R52W	0.997
1:20485238:C:G	G48R	0.997
1:20485246:G:T	P45H	0.997
1:20483698:A:G	I63T	0.996
1:20483710:T:A	E59V	0.996
1:20485218:C:A	K54N	0.996
1:20485218:C:G	K54N	0.996
1:20485229:C:T	G51S	0.996
1:20485237:C:A	G48V	0.996
1:20485243:T:A	K46M	0.996

dbSNP variants (sampled 300 via entrez): RS1000278214 (1:20485595 G>A), RS1000558786 (1:20485701 C>G), RS1001369413 (1:20486011 G>A,C,T), RS1001443157 (1:20485629 C>G,T), RS1002437847 (1:20484364 TACC>T), RS1003110365 (1:20486887 C>A), RS1003166566 (1:20486610 G>A,T), RS1003220623 (1:20484647 C>T), RS1004267266 (1:20487710 C>A), RS1004346501 (1:20482204 G>A), RS1004391096 (1:20487317 G>A), RS1004725963 (1:20484997 G>A), RS1006011718 (1:20486999 G>A), RS1006091397 (1:20483314 T>C), RS1007245682 (1:20484105 C>G)

Disease associations

OMIM: gene MIM:614986 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006269_684	General cognitive ability	8.000000e-10
GCST010002_378	Refractive error	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12023000	CAMK2N1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	7
Estradiol	affects cotreatment, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression	3
Air Pollutants	decreases expression, increases abundance	3
Tretinoin	decreases expression, increases expression	3
bisphenol A	decreases expression, affects expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Cisplatin	affects expression, decreases expression	2
Lead	affects methylation, affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
propionaldehyde	decreases expression	1
beta-lapachone	increases expression	1
arsenite	decreases methylation	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dimethylarsinous acid	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1

Clinical trials (associated diseases)

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