CAMK2N2

Summary

CAMK2N2 (calcium/calmodulin dependent protein kinase II inhibitor 2, HGNC:24197) is a protein-coding gene on chromosome 3q27.1, encoding Calcium/calmodulin-dependent protein kinase II inhibitor 2 (Q96S95). Potent and specific cellular inhibitor of CaM-kinase II (CAMK2).

This gene encodes a protein that is highly similar to the rat CaM-KII inhibitory protein, an inhibitor of calcium/calmodulin-dependent protein kinase II (CAMKII). CAMKII regulates numerous physiological functions, including neuronal synaptic plasticity through the phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate (AMPA) receptors. Studies of the similar protein in rat suggest that this protein may function as a negative regulator of CaM-KII and may act to inhibit the phosphorylation of AMPA receptors.

Source: NCBI Gene 94032 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_033259

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24197
Approved symbol	CAMK2N2
Name	calcium/calmodulin dependent protein kinase II inhibitor 2
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Aliases	CaM-KIIN
Ensembl gene	ENSG00000163888
Ensembl biotype	protein_coding
OMIM	608721
Entrez	94032

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000296238

RefSeq mRNA: 1 — MANE Select: NM_033259 NM_033259

CCDS: CCDS3257

Canonical transcript exons

ENST00000296238 — 2 exons

Exon	Start	End
ENSE00001079415	184261117	184261553
ENSE00001260429	184259213	184260227

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 95.28.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7001 / max 136.3958, expressed in 895 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45881	1.3853	429
45885	1.1224	455
45883	0.8857	298
45884	0.8132	329
45886	0.2299	122
45878	0.1222	60
45879	0.0967	40
45880	0.0447	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	95.28	gold quality
hypothalamus	UBERON:0001898	94.92	gold quality
cerebellar cortex	UBERON:0002129	94.54	gold quality
cerebellar hemisphere	UBERON:0002245	94.53	gold quality
cerebellum	UBERON:0002037	93.64	gold quality
amygdala	UBERON:0001876	92.73	gold quality
right frontal lobe	UBERON:0002810	92.63	gold quality
anterior cingulate cortex	UBERON:0009835	91.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.43	gold quality
prefrontal cortex	UBERON:0000451	91.06	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.39	gold quality
frontal cortex	UBERON:0001870	89.13	gold quality
neocortex	UBERON:0001950	88.96	gold quality
primary visual cortex	UBERON:0002436	88.17	gold quality
temporal lobe	UBERON:0001871	87.75	gold quality
substantia nigra	UBERON:0002038	87.71	gold quality
cerebral cortex	UBERON:0000956	87.41	gold quality
adenohypophysis	UBERON:0002196	87.32	gold quality
pituitary gland	UBERON:0000007	87.02	gold quality
brain	UBERON:0000955	86.90	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.77	gold quality
body of pancreas	UBERON:0001150	86.71	gold quality
midbrain	UBERON:0001891	86.55	gold quality
forebrain	UBERON:0001890	86.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.98	gold quality
occipital lobe	UBERON:0002021	84.50	gold quality
nucleus accumbens	UBERON:0001882	84.10	gold quality
putamen	UBERON:0001874	83.94	gold quality
Ammon’s horn	UBERON:0001954	83.44	gold quality
spinal cord	UBERON:0002240	83.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting CAMK2N2, 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-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-548C-3P	99.99	74.01	7587
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-3960	99.41	66.11	96
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-7160-5P	99.11	67.17	2207

Literature-anchored findings (GeneRIF, showing 4)

• We show that CaMKII N beta expression is differentially regulated by novelty and contextual fear conditioning, providing further insight into molecular basis of fear LTM. (PMID:20487031)
• Murine double minute 2 (MDM2) protein levels were decreased in AD cells relative to control lymphoblasts, suggesting an impairment of FOXO3a degradation. (PMID:23153928)
• Mutant FUS-DeltaNLS increased calcium/calmodulin-dependent protein kinase II inhibitor 2 (CAMK2N2) at both mRNA and protein levels. (PMID:23545117)
• Functional study of the rat homolog (PMID:9724800)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	camk2n1a	ENSDARG00000025855
danio_rerio	camk2n2	ENSDARG00000111102
mus_musculus	Camk2n2	ENSMUSG00000051146
rattus_norvegicus	Camk2n2	ENSRNOG00000076327

Paralogs (1): CAMK2N1 (ENSG00000162545)

Protein

Protein identifiers

Calcium/calmodulin-dependent protein kinase II inhibitor 2 — Q96S95 (reviewed: Q96S95)

Alternative names: CaM-KII inhibitory protein

All UniProt accessions (1): Q96S95

UniProt curated annotations — full annotation on UniProt →

Function. Potent and specific cellular inhibitor of CaM-kinase II (CAMK2). Traps Ca(2+)/calmodulin on CAMK2.

Subunit / interactions. Interacts with CAMK2A and CAMK2B in the presence of Ca(2+)/calmodulin or after autophosphorylation.

Subcellular location. Nucleus. Cytoplasm. Cytosol. Synapse.

Tissue specificity. Highly Expressed in keyhole limpet hemocyanin-stimulated dendritic cell (DC) and weakly expressed in unstimulated mature and immature DC. Highly expressed in kidney and liver. Moderately expressed in heart, skeletal muscle, and placenta. Weakly expressed in the small intestine.

Similarity. Belongs to the CAMK2N family.

RefSeq proteins (1): NP_150284* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026779	Camk2n	Family

Pfam: PF15170

UniProt features (3 total): region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96S95-F1	70.14	0.04

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 59 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WANG_CLIM2_TARGETS_UP, BENPORATH_ES_WITH_H3K27ME3, TGCACTT_MIR519C_MIR519B_MIR519A, GTGTTGA_MIR505, TGTGTGA_MIR377, AGGAGTG_MIR483, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, CAGCCTC_MIR4855P, GOCC_SYNAPSE, POS_HISTAMINE_RESPONSE_NETWORK, GOMF_PROTEIN_SERINE_THREONINE_KINASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GCACTTT_MIR175P_MIR20A_MIR106A_MIR106B_MIR20B_MIR519D, GOMF_ENZYME_REGULATOR_ACTIVITY

GO Biological Process (0):

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): nucleus (GO:0005634), cytosol (GO:0005829), synapse (GO:0045202), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
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
intracellular membrane-bounded organelle	1
cytoplasm	1
cell junction	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAMK2N2	CAMK2B	Q13554	816
CAMK2N2	CAMK2A	Q9UQM7	770
CAMK2N2	CALM1	P02593	669
CAMK2N2	CALML3	P27482	648
CAMK2N2	CALML6	Q8TD86	648
CAMK2N2	CALML4	Q96GE6	648
CAMK2N2	CALML5	Q9NZT1	648
CAMK2N2	LRRC7	Q96NW7	458
CAMK2N2	DUSP7	Q16829	437
CAMK2N2	RIMBP2	O15034	435
CAMK2N2	DUSP22	Q9NRW4	419
CAMK2N2	UNC13C	Q8NB66	414
CAMK2N2	DUSP8	Q13202	413
CAMK2N2	CAMK1G	Q96NX5	394
CAMK2N2	GRIN2B	Q13224	394

IntAct

4 interactions, top by confidence:

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

BioGRID (3): CAMK2N2 (Affinity Capture-MS), CAMK2N2 (Affinity Capture-RNA), CAMK2N2 (Reconstituted Complex)

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	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

453 predictions. Top by Δscore:

Variant	Effect	Δscore
3:184261111:GCGTA:G	donor_loss	1.0000
3:184261112:CGTAC:C	donor_loss	1.0000
3:184261113:GTAC:G	donor_loss	1.0000
3:184261114:TAC:T	donor_loss	1.0000
3:184261116:C:CA	donor_loss	1.0000
3:184261116:CCTCG:C	donor_gain	1.0000
3:184260228:C:CC	acceptor_gain	0.9900
3:184260225:CCA:C	acceptor_gain	0.9800
3:184260226:CAC:C	acceptor_gain	0.9800
3:184260226:CA:C	acceptor_gain	0.9700
3:184260894:T:TA	donor_gain	0.9700
3:184260223:CACCA:C	acceptor_gain	0.9600
3:184260224:ACCAC:A	acceptor_loss	0.9600
3:184260225:CCACT:C	acceptor_loss	0.9600
3:184260226:CACTG:C	acceptor_loss	0.9600
3:184260227:ACTG:A	acceptor_loss	0.9600
3:184260229:T:A	acceptor_loss	0.9600
3:184260231:C:CT	acceptor_gain	0.9600
3:184260724:T:TA	donor_gain	0.9600
3:184261213:A:T	donor_gain	0.9600
3:184261115:A:AC	donor_gain	0.9400
3:184261116:C:CC	donor_gain	0.9400
3:184260224:ACCA:A	acceptor_gain	0.9300
3:184260225:CCAC:C	acceptor_gain	0.9300
3:184260747:C:A	donor_gain	0.9200
3:184261116:CCT:C	donor_gain	0.9200
3:184261262:GCT:G	donor_gain	0.9200
3:184261274:G:GT	donor_gain	0.9100
3:184260729:C:A	donor_gain	0.9000
3:184261265:G:GG	donor_gain	0.9000

AlphaMissense

513 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:184261131:C:T	G52D	0.999
3:184260216:C:G	D61H	0.998
3:184261131:C:A	G52V	0.998
3:184261132:C:G	G52R	0.998
3:184261134:A:C	I51S	0.998
3:184261134:A:T	I51N	0.998
3:184261143:A:T	L48Q	0.998
3:184261145:C:A	K47N	0.998
3:184261145:C:G	K47N	0.998
3:184261147:T:C	K47E	0.998
3:184260215:T:A	D61V	0.997
3:184261132:C:A	G52C	0.997
3:184261134:A:G	I51T	0.997
3:184261140:C:T	G49D	0.996
3:184261149:G:T	P46H	0.996
3:184260216:C:A	D61Y	0.994
3:184261143:A:G	L48P	0.994
3:184261146:T:A	K47M	0.994
3:184261150:G:T	P46T	0.994
3:184261204:A:G	C28R	0.994
3:184261281:G:A	S2F	0.994
3:184260215:T:G	D61A	0.993
3:184261121:C:A	K55N	0.993
3:184261121:C:G	K55N	0.993
3:184261150:G:A	P46S	0.993
3:184261146:T:G	K47T	0.992
3:184260206:A:T	I64K	0.991
3:184260218:T:A	E60V	0.991
3:184261141:C:G	G49R	0.991
3:184260221:A:T	I59N	0.990

dbSNP variants (sampled 300 via entrez): RS1002374443 (3:184263370 A>G), RS1002762361 (3:184260473 A>G), RS1002792509 (3:184260144 C>A,G,T), RS1002941412 (3:184260323 G>A,T), RS1002992139 (3:184259496 G>T), RS1005564656 (3:184259820 C>G), RS1005578383 (3:184258999 C>T), RS1006676849 (3:184259691 G>A), RS1006939891 (3:184259907 G>A), RS1007019134 (3:184262995 G>A,C), RS1007413319 (3:184261062 G>A,T), RS1007480804 (3:184262602 C>T), RS1008340937 (3:184260980 C>A,G,T), RS1008610475 (3:184261216 G>A), RS1009875651 (3:184262931 C>T)

Disease associations

OMIM: gene MIM:608721 | 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
GCST001469_1	Major depressive disorder	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
zinc chromate	decreases expression, increases abundance	1
pentanal	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Diazinon	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	increases expression	1
Aflatoxin B1	decreases expression, increases expression	1
Cadmium Chloride	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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