Entrez ID	Official symbol	Synonyms	Description	Location	Type of protein	External annotation
10645	CAMKK2	CAMKK, CAMKKB	calcium/calmodulin dependent protein kinase kinase 2	12q24.31	protein-coding	Genecard

uniprot_summary

refseq_summary

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.

The product of this gene belongs to the Serine/Threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. The major isoform of this gene plays a role in the calcium/calmodulin-dependent (CaM) kinase cascade by phosphorylating the downstream kinases CaMK1 and CaMK4. Protein products of this gene also phosphorylate AMP-activated protein kinase (AMPK). This gene has its strongest expression in the brain and influences signalling cascades involved with learning and memory, neuronal differentiation and migration, neurite outgrowth, and synapse formation. Alternative splicing results in multiple transcript variants encoding distinct isoforms. The identified isoforms differ in their ability to undergo autophosphorylation and to phosphorylate downstream kinases.

Caregory	Description	Value	Value range ( Low - High )	Comment
PLI	The probability of being loss-of-function (LoF) intolerant	0.503	[0, ..., 1]	Genes with high pLI scores (pLI ≥ 0.9) are extremely LoF intolerant, whereby genes with low pLI scores (pLI ≤ 0.1) are LoF tolerant. The score is calculated based on high-quality exome sequence data (ExAC) for 60,706 individuals of diverse ethnicities.
Haploinsufficiency (HI) score rank	Predicted probability of exhibiting haploinsufficiency		[100, ..., 1]	High ranks (e.g. 0-10%) indicate a gene is more likely to exhibit haploinsufficiency, low ranks (e.g. 90-100%) indicate a gene is more likely to NOT exhibit haploinsufficiency (DECIPHER, PMID: 20976243). haploinsufficiency means a single functional copy of a gene is insufficient to maintain its normal function and is extremely intolerant of LoF variation.
Gene brain expressed	Queried gene is expressed in brain tissues	True	[False, True]	The gene expression data are extracted from GTEx v7 and BrainSpan. A gene with the expression value of (log 2 based (TPM+1)) at least 1 TPM/RPKM/FPKM in one or more tissues related to the brain is considered brain-expressed.
Protein brain expressed	Queried protein is expressed in brain tissues	True	[False, True]	The protein expression data are extracted from ProteomicsDB (v2018.09). A protein with the expression value of (log based 10 (iBAQ intensity)) at least 0.5 in one or more tissues related to the brain is considered brain-expressed protein.
Carrying LoF DNMs	Number of loss-of-function DNMs hit the queried gene	0 (Case)	[0, ..., 67] with average of 0.160	Loss of function (LoF) mutations include frameshift indels, nonsense (stop-gained) and splice-site mutations, which can result in the gene product having less or no function and can have deleterious consequences.
		0 (Control)	[0, ..., 6] with average of 0.044
Carrying missense DNMs	Number of missense DNMs hit the queried gene	1 (Case)	[0, ..., 55] with average of 0.846	Missense mutations can result in changes in protein sequences, but are commonly considered to have less deleterious impacts than LoF mutations.
		1 (Control)	[0, ..., 21] with average of 0.300
FMRP binding targets	FMRP inteacting parters	True	[False, True]	FMRP loss of function causes Fragile X syndrome (FXS). The binding targets identified crosslinking immunoprecipitation (HITS-CLIP) in mouse brains (PMID:21784246). Many FMRP targets are among genes implicated in different neuropsychiatric diseases, such as autism, schizophrenia.
Postsynaptic density (PSD)	Protein associates with postsynaptic membranes of excitatory synapses	False	[False, True]	Abnormalities with PSD proteins are linked to various neuropsychiatric diseases including neurodevelopmental disorders.
Human essential genes	-	False	[False, True]	Genes are thought to be critical for human survival.