MAPKAP1

MAPK associated protein 1, the group of MTOR complex 2

Basic information

Region (hg38): 9:125437392-125707234

Links

ENSG00000119487 ∙ NCBI:79109 ∙ OMIM:610558 ∙ HGNC:18752 ∙ Uniprot:Q9BPZ7 ∙ 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 MAPKAP1 gene.

• Inborn genetic diseases (7 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAPKAP1 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	3	4
missense			7			7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	7	1	4

Variants in MAPKAP1

This is a list of pathogenic ClinVar variants found in the MAPKAP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-125438945-T-G		not specified	Uncertain significance (Nov 08, 2022)
9-125438992-C-T			Benign (Jun 04, 2018)
9-125444517-T-C		not specified	Uncertain significance (Jan 23, 2024)
9-125444576-C-T			Benign (Aug 17, 2018)
9-125444590-T-C		not specified	Uncertain significance (Dec 19, 2022)
9-125468046-C-A		not specified	Uncertain significance (Jan 16, 2024)
9-125506357-G-C		not specified	Uncertain significance (Feb 28, 2024)
9-125543111-C-T			Benign (Jul 21, 2018)
9-125559741-G-A		not specified	Uncertain significance (Dec 28, 2023)
9-125585625-C-T		not specified	Uncertain significance (Dec 02, 2022)
9-125585694-C-G		not specified	Uncertain significance (Oct 20, 2023)
9-125644709-G-C			Benign (Apr 29, 2020)
9-125657739-C-G		not specified	Uncertain significance (Aug 19, 2023)
9-125657776-C-T		not specified	Uncertain significance (Jan 02, 2024)
9-125672477-T-C		not specified	Uncertain significance (Aug 12, 2022)
9-125672480-A-G		not specified	Uncertain significance (Nov 18, 2023)
9-125672527-C-T			Likely benign (Jul 16, 2018)
9-125672531-C-T		not specified	Uncertain significance (Jan 05, 2022)
9-125672544-G-C		not specified	Uncertain significance (Feb 17, 2023)
9-125672553-T-C		not specified	Uncertain significance (Mar 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAPKAP1	protein_coding	protein_coding	ENST00000265960	11	269842

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000863	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.83	164	302	0.542	0.0000171	3436
Missense in Polyphen		39	107.47	0.36288		1212
Synonymous	0.784	111	122	0.910	0.00000792	964
Loss of Function	4.99	1	31.0	0.0323	0.00000187	333

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000356	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient- insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Within mTORC2, MAPKAP1 is required for complex formation and mTORC2 kinase activity. MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation. Inhibits HRAS and KRAS signaling. Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription. Involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex. {ECO:0000269|PubMed:15988011, ECO:0000269|PubMed:16962653, ECO:0000269|PubMed:17043309, ECO:0000269|PubMed:17054722, ECO:0000269|PubMed:17303383, ECO:0000269|PubMed:23727834}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Target Of Rapamycin (TOR) Signaling;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Steatosis AOP;Interferon type I signaling pathways;Disease;Signal Transduction;Gene expression (Transcription);VEGFA-VEGFR2 Pathway;Generic Transcription Pathway;CD28 dependent PI3K/Akt signaling;CD28 co-stimulation;Costimulation by the CD28 family;RNA Polymerase II Transcription;Immune System;Adaptive Immune System;insulin Mam;CXCR4-mediated signaling events;ErbB1 downstream signaling;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;PIP3 activates AKT signaling;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Signaling by VEGF;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;mTOR signaling pathway;Diseases of signal transduction;CXCR3-mediated signaling events;Class I PI3K signaling events mediated by Akt;VEGFR2 mediated vascular permeability (Consensus)

Recessive Scores

• pRec: 0.275

Intolerance Scores

• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.5

Haploinsufficiency Scores

• pHI: 0.253
• hipred: Y
• hipred_score: 0.825
• ghis: 0.667

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mapkap1
• Phenotype: 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; vision/eye phenotype; growth/size/body region phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: mapkap1
• Affected structure: axial mesoderm
• Phenotype tag: abnormal
• Phenotype quality: increased width

Gene ontology

• Biological process: substantia nigra development;establishment or maintenance of actin cytoskeleton polarity;activation of protein kinase B activity;positive regulation of peptidyl-serine phosphorylation;TORC2 signaling;negative regulation of Ras protein signal transduction;regulation of cellular response to oxidative stress
• Cellular component: nucleoplasm;cytoplasm;Golgi apparatus;cytosol;plasma membrane;cytoplasmic vesicle;TORC2 complex
• Molecular function: protein binding;phosphatidylinositol-4,5-bisphosphate binding;phosphatidylinositol-3,4,5-trisphosphate binding;Ras GTPase binding;protein kinase binding;phosphatidylinositol-3,4-bisphosphate binding;phosphatidic acid binding;phosphatidylinositol-3,5-bisphosphate binding