CAMK4

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

Basic information

Region (hg38): 5:111223652-111494886

Links

ENSG00000152495 ∙ NCBI:814 ∙ OMIM:114080 ∙ HGNC:1464 ∙ Uniprot:Q16566 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAMK4 gene.

• Inborn genetic diseases (15 variants)
• not provided (9 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAMK4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense	1		15	1	2	19
nonsense			1			1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region					1	1
non coding						0
Total	1	0	18	1	3

Variants in CAMK4

This is a list of pathogenic ClinVar variants found in the CAMK4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-111224521-C-G		not specified	Uncertain significance (Feb 10, 2022)
5-111224545-C-T		not specified	Likely benign (Aug 28, 2023)
5-111224572-C-G		not specified	Uncertain significance (Feb 22, 2023)
5-111224604-G-T		not specified	Uncertain significance (Jul 13, 2021)
5-111224643-C-T		not specified	Uncertain significance (Sep 17, 2021)
5-111374883-GTTC-G			Uncertain significance (Apr 01, 2023)
5-111374914-T-C			Uncertain significance (Feb 04, 2023)
5-111376875-A-G		not specified	Uncertain significance (Apr 04, 2023)
5-111394739-G-A		not specified	Uncertain significance (Jul 20, 2021)
5-111446758-G-A			Benign (Jul 04, 2018)
5-111449207-T-G			Benign (Oct 01, 2022)
5-111473355-A-G		not specified	Uncertain significance (Sep 12, 2023)
5-111473377-C-G		not specified	Uncertain significance (May 26, 2022)
5-111478483-A-T		not specified	Uncertain significance (Aug 03, 2022)
5-111478500-A-G		not specified	Uncertain significance (Jan 31, 2022)
5-111482806-G-A			Uncertain significance (May 26, 2022)
5-111482885-T-C			Pathogenic (Jun 29, 2023)
5-111482896-C-T		not specified	Uncertain significance (May 12, 2020)
5-111482929-A-G		not specified	Uncertain significance (Jan 26, 2023)
5-111482938-G-A		Involuntary movements;Intellectual disability	Conflicting classifications of pathogenicity (Jan 24, 2019)
5-111484113-C-G		not specified	Uncertain significance (Feb 28, 2023)
5-111484146-G-A		not specified	Uncertain significance (Jan 30, 2024)
5-111484158-A-G		not specified	Uncertain significance (Feb 17, 2024)
5-111484210-G-T		not specified	Uncertain significance (Jan 22, 2024)
5-111484269-A-G		not specified	Uncertain significance (Oct 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAMK4	protein_coding	protein_coding	ENST00000282356	11	271234

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.510	0.490	125740	0	7	125747	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.81	177	259	0.683	0.0000133	3069
Missense in Polyphen		44	98.08	0.44861		1132
Synonymous	0.392	92	96.9	0.949	0.00000510	921
Loss of Function	3.23	4	19.3	0.207	9.01e-7	246

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000293	0.0000293
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000555	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000357	0.0000352
Middle Eastern	0.0000555	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and regulates, mainly by phosphorylation, the activity of several transcription activators, such as CREB1, MEF2D, JUN and RORA, which play pivotal roles in immune response, inflammation, and memory consolidation. In the thymus, regulates the CD4(+)/CD8(+) double positive thymocytes selection threshold during T-cell ontogeny. In CD4 memory T-cells, is required to link T-cell antigen receptor (TCR) signaling to the production of IL2, IFNG and IL4 (through the regulation of CREB and MEF2). Regulates the differentiation and survival phases of osteoclasts and dendritic cells (DCs). Mediates DCs survival by linking TLR4 and the regulation of temporal expression of BCL2. Phosphorylates the transcription activator CREB1 on 'Ser-133' in hippocampal neuron nuclei and contribute to memory consolidation and long term potentiation (LTP) in the hippocampus. Can activate the MAP kinases MAPK1/ERK2, MAPK8/JNK1 and MAPK14/p38 and stimulate transcription through the phosphorylation of ELK1 and ATF2. Can also phosphorylate in vitro CREBBP, PRM2, MEF2A and STMN1/OP18. {ECO:0000269|PubMed:10617605, ECO:0000269|PubMed:17909078, ECO:0000269|PubMed:18829949, ECO:0000269|PubMed:7961813, ECO:0000269|PubMed:8065343, ECO:0000269|PubMed:8855261, ECO:0000269|PubMed:8980227, ECO:0000269|PubMed:9154845}.
• Pathway: Aldosterone synthesis and secretion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Long-term potentiation - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Alcoholism - Homo sapiens (human);Energy Metabolism;Regulation of Microtubule Cytoskeleton;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Common Pathways Underlying Drug Addiction;Mitochondrial Gene Expression;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Signal Transduction;regulation of pgc-1a;stathmin and breast cancer resistance to antimicrotubule agents;nfat and hypertrophy of the heart ;CaMK IV-mediated phosphorylation of CREB;Calmodulin induced events;CaM pathway;Neuronal System;Signaling events mediated by HDAC Class II;DAG and IP3 signaling;Ca-dependent events;PLC beta mediated events;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;Activation of CaMK IV;CREB phosphorylation through the activation of CaMKK;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;GPCR downstream signalling;ca-calmodulin-dependent protein kinase activation;Intracellular signaling by second messengers;Regulation of nuclear beta catenin signaling and target gene transcription;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Trk receptor signaling mediated by PI3K and PLC-gamma;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.132

Intolerance Scores

• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.6

Haploinsufficiency Scores

• pHI: 0.174
• hipred: Y
• hipred_score: 0.686
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.954

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Camk4
• Phenotype: endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype

Zebrafish Information Network

• Gene name: camk4
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: adaptive immune response;myeloid dendritic cell cytokine production;protein phosphorylation;inflammatory response;signal transduction;long-term memory;peptidyl-serine phosphorylation;regulation of T cell differentiation in thymus;intracellular signal transduction;myeloid dendritic cell differentiation;regulation of osteoclast differentiation;positive regulation of transcription, DNA-templated;protein autophosphorylation
• Cellular component: fibrillar center;nucleus;nucleoplasm;cytoplasm;cytosol;extracellular exosome;postsynapse;glutamatergic synapse
• Molecular function: calmodulin-dependent protein kinase activity;calmodulin binding;ATP binding;calcium-dependent protein serine/threonine kinase activity