MAP3K9

mitogen-activated protein kinase kinase kinase 9, the group of Mitogen-activated protein kinase kinase kinases

Basic information

Region (hg38): 14:70722526-70809534

Previous symbols: [ "MLK1" ]

Links

ENSG00000006432 ∙ NCBI:4293 ∙ OMIM:600136 ∙ HGNC:6861 ∙ Uniprot:P80192 ∙ 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 MAP3K9 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP3K9 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				3		3
missense			51			51
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	51	3	0

Variants in MAP3K9

This is a list of pathogenic ClinVar variants found in the MAP3K9 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-70730519-G-A		not specified	Uncertain significance (Jul 07, 2022)
14-70730520-G-A		not specified	Uncertain significance (Jun 10, 2024)
14-70730546-G-A		not specified	Uncertain significance (Feb 12, 2024)
14-70730612-G-A		not specified	Uncertain significance (Jun 07, 2023)
14-70730627-C-G		not specified	Uncertain significance (Jul 25, 2023)
14-70730628-T-A		not specified	Uncertain significance (May 09, 2022)
14-70730694-G-A		not specified	Uncertain significance (Jun 18, 2021)
14-70730725-C-A		not specified	Uncertain significance (Dec 21, 2023)
14-70730786-G-T		not specified	Uncertain significance (Feb 10, 2022)
14-70730787-G-T		not specified	Uncertain significance (Feb 10, 2022)
14-70730840-C-T		not specified	Uncertain significance (Mar 07, 2024)
14-70732548-G-A		not specified	Uncertain significance (Jun 24, 2022)
14-70732587-C-A		not specified	Uncertain significance (Aug 15, 2023)
14-70732629-G-A		not specified	Uncertain significance (May 07, 2024)
14-70732632-G-A		not specified	Uncertain significance (Jan 23, 2024)
14-70732662-G-A		not specified	Uncertain significance (Sep 14, 2023)
14-70732710-G-A		not specified	Uncertain significance (Feb 21, 2024)
14-70732724-T-C		not specified	Uncertain significance (May 24, 2024)
14-70732774-G-T		not specified	Uncertain significance (Mar 01, 2024)
14-70732868-A-G		not specified	Uncertain significance (Jul 13, 2022)
14-70732937-G-T		not specified	Uncertain significance (Jun 16, 2023)
14-70732988-C-T		not specified	Uncertain significance (Oct 22, 2021)
14-70733009-G-A		not specified	Uncertain significance (May 15, 2023)
14-70733022-G-A		not specified	Uncertain significance (Oct 20, 2021)
14-70733106-C-T		not specified	Uncertain significance (Apr 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP3K9	protein_coding	protein_coding	ENST00000555993	13	87009

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.118	0.882	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.27	575	667	0.862	0.0000413	7241
Missense in Polyphen		223	285.52	0.78102		2923
Synonymous	1.65	231	265	0.871	0.0000153	2323
Loss of Function	4.67	11	44.7	0.246	0.00000258	483

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000245	0.000242
Ashkenazi Jewish	0.00	0.00
East Asian	0.000115	0.000109
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000160	0.000158
Middle Eastern	0.000115	0.000109
South Asian	0.0000987	0.0000980
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Plays also a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. {ECO:0000269|PubMed:11416147, ECO:0000269|PubMed:15610029}.
• Disease: DISEASE: Note=May play a role in esophageal cancer susceptibility and/or development.
• Pathway: EGF-Core;Angiopoietin Like Protein 8 Regulatory Pathway;Oxidative Damage;p38 MAPK Signaling Pathway;Insulin Signaling;p38 mapk signaling pathway;IL-7 signaling;JAK STAT pathway and regulation;EPO signaling;VEGF (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.264
• rvis_EVS: -1.55
• rvis_percentile_EVS: 3.31

Haploinsufficiency Scores

• pHI: 0.148
• hipred: Y
• hipred_score: 0.605
• ghis: 0.598

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.738

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map3k9
• Phenotype: normal phenotype

Gene ontology

• Biological process: MAPK cascade;protein phosphorylation;apoptotic process;activation of JNKK activity;activation of JUN kinase activity;positive regulation of apoptotic process;protein autophosphorylation
• Cellular component: cellular_component
• Molecular function: protein serine/threonine kinase activity;JUN kinase kinase kinase activity;MAP kinase kinase activity;protein binding;ATP binding;protein homodimerization activity