CAMKK2

calcium/calmodulin dependent protein kinase kinase 2

Basic information

Region (hg38): 12:121237674-121298308

Links

ENSG00000110931 ∙ NCBI:10645 ∙ OMIM:615002 ∙ HGNC:1470 ∙ Uniprot:Q96RR4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAMKK2 gene.

• Inborn genetic diseases (19 variants)
• not provided (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAMKK2 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					6	6
missense			16	3		19
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	17	3	6

Variants in CAMKK2

This is a list of pathogenic ClinVar variants found in the CAMKK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-121240713-T-C		not specified	Uncertain significance (Apr 04, 2023)
12-121240713-T-TGGCCTCCTCC			Uncertain significance (Aug 01, 2019)
12-121240724-G-A		not specified	Likely benign (Aug 21, 2023)
12-121240727-C-T		not specified	Likely benign (May 03, 2023)
12-121240757-G-A		not specified	Uncertain significance (Feb 21, 2024)
12-121240764-G-C		not specified	Uncertain significance (Jan 12, 2024)
12-121245212-C-T		not specified	Uncertain significance (Mar 04, 2024)
12-121245213-G-A		not specified	Uncertain significance (Jul 22, 2022)
12-121249870-C-T		not specified	Uncertain significance (Sep 16, 2021)
12-121249958-C-T			Benign (Jul 31, 2018)
12-121250025-T-A		not specified	Uncertain significance (Aug 02, 2021)
12-121253327-G-A			Benign (Jul 31, 2018)
12-121253338-C-A		not specified	Uncertain significance (May 06, 2022)
12-121255566-G-A			Benign (Jun 06, 2017)
12-121255800-G-A		not specified	Likely benign (Nov 29, 2023)
12-121263885-C-T		not specified	Uncertain significance (Jun 29, 2022)
12-121263900-C-A		not specified	Uncertain significance (Nov 18, 2022)
12-121274076-C-T		not specified	Uncertain significance (Oct 05, 2023)
12-121274077-G-A			Benign (Jul 10, 2018)
12-121274100-G-A		not specified	Uncertain significance (Nov 08, 2021)
12-121274128-G-A			Benign (Jul 16, 2018)
12-121274136-C-T		not specified	Uncertain significance (May 03, 2023)
12-121274153-G-A		not specified	Uncertain significance (Mar 16, 2022)
12-121274156-G-A		not specified	Uncertain significance (May 13, 2022)
12-121274173-G-A			Benign (Apr 20, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAMKK2	protein_coding	protein_coding	ENST00000324774	16	60615

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0916	0.908	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.59	283	369	0.767	0.0000241	3781
Missense in Polyphen		52	87.195	0.59636		935
Synonymous	-0.455	165	158	1.05	0.0000109	1185
Loss of Function	3.80	8	30.7	0.261	0.00000162	355

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000178
Ashkenazi Jewish	0.00	0.00
East Asian	0.000165	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000776	0.0000703
Middle Eastern	0.000165	0.000163
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin- binding domain are inactive. Efficiently phosphorylates 5'-AMP- activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching. {ECO:0000250, ECO:0000269|PubMed:11395482, ECO:0000269|PubMed:12935886, ECO:0000269|PubMed:21957496, ECO:0000269|PubMed:9662074}.
• Pathway: Oxytocin signaling pathway - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Alcoholism - Homo sapiens (human);AMP-activated Protein Kinase (AMPK) Signaling;VEGFA-VEGFR2 Signaling Pathway;regulation of pgc-1a;nfat and hypertrophy of the heart ;Ghrelin;fmlp induced chemokine gene expression in hmc-1 cells;ca-calmodulin-dependent protein kinase activation;Signaling events mediated by VEGFR1 and VEGFR2 (Consensus)

Recessive Scores

• pRec: 0.234

Intolerance Scores

• loftool: 0.605
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.82

Haploinsufficiency Scores

• pHI: 0.518
• hipred: Y
• hipred_score: 0.756
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Camkk2
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: MAPK cascade;positive regulation of protein phosphorylation;protein phosphorylation;peptidyl-tyrosine phosphorylation;calcium-mediated signaling;cellular response to reactive oxygen species;regulation of protein kinase activity;positive regulation of transcription, DNA-templated;protein autophosphorylation;CAMKK-AMPK signaling cascade;positive regulation of autophagy of mitochondrion
• Cellular component: nucleus;cytosol;cell projection
• Molecular function: calmodulin-dependent protein kinase activity;protein tyrosine kinase activity;calcium ion binding;calmodulin binding;ATP binding