MAP3K12

mitogen-activated protein kinase kinase kinase 12, the group of Mitogen-activated protein kinase kinase kinases

Basic information

Region (hg38): 12:53479669-53500063

Previous symbols: [ "ZPK" ]

Links

ENSG00000139625 ∙ NCBI:7786 ∙ OMIM:600447 ∙ HGNC:6851 ∙ Uniprot:Q12852 ∙ 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 MAP3K12 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP3K12 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						0
missense			24		1	25
nonsense						0
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	26	0	1

Variants in MAP3K12

This is a list of pathogenic ClinVar variants found in the MAP3K12 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-53481970-TGG-T			Uncertain significance (Mar 01, 2022)
12-53482039-C-T		not specified	Uncertain significance (Jun 29, 2023)
12-53482110-C-A		not specified	Uncertain significance (Jun 10, 2022)
12-53482620-G-A		not specified	Uncertain significance (Jan 26, 2023)
12-53482632-C-A		not specified	Uncertain significance (Oct 03, 2022)
12-53482641-C-T		not specified	Uncertain significance (May 07, 2024)
12-53482663-C-G		not specified	Uncertain significance (Nov 09, 2023)
12-53482779-G-T		not specified	Uncertain significance (May 01, 2024)
12-53482786-C-T			Benign (Jun 27, 2018)
12-53482816-C-T		not specified	Uncertain significance (Feb 10, 2022)
12-53482822-C-T		not specified	Uncertain significance (Jul 09, 2021)
12-53482836-C-T		not specified	Uncertain significance (Dec 06, 2021)
12-53482843-G-A		not specified	Uncertain significance (Mar 22, 2022)
12-53482867-G-T		not specified	Uncertain significance (Apr 12, 2022)
12-53482879-A-G		not specified	Uncertain significance (Aug 06, 2021)
12-53482894-G-A		not specified	Uncertain significance (Apr 25, 2022)
12-53483073-T-C		not specified	Uncertain significance (Jun 27, 2022)
12-53483082-C-T		not specified	Uncertain significance (Feb 06, 2023)
12-53483088-C-T		not specified	Uncertain significance (Dec 19, 2023)
12-53483356-T-G		not specified	Uncertain significance (Mar 24, 2023)
12-53483377-G-T		not specified	Uncertain significance (Apr 08, 2022)
12-53483388-T-C		not specified	Uncertain significance (Jun 24, 2022)
12-53484322-G-C		not specified	Uncertain significance (May 14, 2024)
12-53484342-G-A		not specified	Uncertain significance (Jun 13, 2024)
12-53485096-T-C		Falls;Delayed speech and language development	Uncertain significance (Nov 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP3K12	protein_coding	protein_coding	ENST00000547035	13	19574

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.45e-7	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.99	332	525	0.633	0.0000306	5687
Missense in Polyphen		60	172.71	0.3474		1939
Synonymous	-1.43	234	208	1.13	0.0000111	1947
Loss of Function	5.96	0	41.3	0.00	0.00000254	441

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000364	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro.
• Pathway: MAPK signaling pathway - Homo sapiens (human);EGF-Core;MAPK Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;MAPK Cascade;Insulin Signaling;mapkinase signaling pathway;IL-7 signaling;JAK STAT pathway and regulation;EPO signaling;VEGF;Regulation of p38-alpha and p38-beta (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.0529
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.72

Haploinsufficiency Scores

• pHI: 0.399
• hipred: Y
• hipred_score: 0.775
• ghis: 0.598

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.957

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map3k12
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; vision/eye 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); 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)

Gene ontology

• Biological process: MAPK cascade;protein phosphorylation;JNK cascade;activation of JNKK activity;activation of JUN kinase activity;histone phosphorylation;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;intracellular signal transduction;positive regulation of transcription, DNA-templated;protein autophosphorylation;positive regulation of ERK1 and ERK2 cascade;negative regulation of motor neuron apoptotic process
• Cellular component: cytoplasm;cytosol;plasma membrane;membrane;growth cone
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;JUN kinase kinase kinase activity;protein binding;ATP binding;protein kinase binding;protein homodimerization activity