GeneBe

CAMK1

protein-coding

calcium/calmodulin dependent protein kinase I, the group of Calmodulin dependent protein kinases

Gene summary

Calcium/calmodulin-dependent protein kinase I is expressed in many tissues and is a component of a calmodulin-dependent protein kinase cascade. Calcium/calmodulin directly activates calcium/calmodulin-dependent protein kinase I by binding to the enzyme and indirectly promotes the phosphorylation and synergistic activation of the enzyme by calcium/calmodulin-dependent protein kinase I kinase. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003656.5

Inheritance

—

ClinVar variants

U:60B:3

Top phenotype

OGG1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr3:9,757,347-9,769,992

External References & Databases

Ensembl (ENSG00000134072)NCBI Gene (8536)OMIM (604998)HGNC:1459GenCCUniProt (Q14012)AlphaFoldClinVar (CAMK1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~12.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CAMK1 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 57
not providedTotal: 2
OGG1-related disorderTotal: 1
Nonpapillary renal cell carcinomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003656.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
 4
missense
58
clinvar
 58
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total00603063
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_003656.5RefSeqNP_003647.111MANE Select
ENST00000256460.8EnsemblENSP00000256460.311MANE Select
ENST00000397277.6EnsemblENSP00000380447.22Standard
ENST00000411972.1EnsemblENSP00000404587.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Aldosterone synthesis and secretion - Homo sapiens (human)
  • Oxytocin signaling pathway - Homo sapiens (human)
  • EGFR Inhibitor Pathway, Pharmacodynamics
  • Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
  • Association Between Physico-Chemical Features and Toxicity Associated Pathways

Biological Process

  • protein phosphorylation
  • nucleocytoplasmic transport
  • cell cycle
  • signal transduction
  • positive regulation of neuron projection development

Molecular Function

  • calmodulin-dependent protein kinase activity
  • protein binding
  • calmodulin binding
  • ATP binding

Cellular Component

  • nucleus
  • cytoplasm
  • postsynaptic density
  • glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000256460
Coding exons
11
Length
12651
Individuals with no LoFs
125712
Homozygous LoFs
0
Heterozygous LoFs
36
Defined
125748
p
0.000143
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.5232012230.9010.00001292444
Missense (PolyPhen)82101.050.811471158
Synonymous-0.07639594.11.010.00000630690
Loss of Function2.211122.30.4940.00000114243

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian0.000270.00027rare
Finnish0.0000920.000092rare
European (Non-Finnish)0.000150.00015rare
South Asian0.000160.00016rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser- 694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser- 498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen- stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I. {ECO:0000250, ECO:0000269|PubMed:11114197, ECO:0000269|PubMed:12193581, ECO:0000269|PubMed:14507913, ECO:0000269|PubMed:14754892, ECO:0000269|PubMed:17056143, ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:20181577}.;

Recessive Scores

pRec
0.187

Intolerance Scores

LoFtool
0.720
RVIS EVS
-0.52
RVIS percentile EVS
21.2

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.684

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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