Entrez ID	Official symbol	Synonyms	Description	Location	Type of protein	External annotation
7867	MAPKAPK3	3PK, MAPKAP-K3, MAPKAP3, MAPKAPK-3, MDPT3, MK-3, MK3	MAPK activated protein kinase 3	3p21.2	protein-coding	Genecard

uniprot_summary

refseq_summary

Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression.

This gene encodes a member of the Ser/Thr protein kinase family. This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This kinase was shown to be activated by growth inducers and stress stimulation of cells. In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of this kinase as an integrative element of signaling in both mitogen and stress responses. This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. Alternate splicing results in multiple transcript variants that encode the same protein.

Flase

Caregory	Description	Value	Value range ( Low - High )	Comment
PLI	The probability of being loss-of-function (LoF) intolerant	-	[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	[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	0 (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.
		0 (Control)	[0, ..., 21] with average of 0.300
FMRP binding targets	FMRP inteacting parters	False	[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.