MAP3K3

mitogen-activated protein kinase kinase kinase 3, the group of Mitogen-activated protein kinase kinase kinases

Basic information

Region (hg38): 17:63622414-63696305

Previous symbols: [ "MEKK3" ]

Links

ENSG00000198909 ∙ NCBI:4215 ∙ OMIM:602539 ∙ HGNC:6855 ∙ Uniprot:Q99759 ∙ 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 MAP3K3 gene.

• Inborn genetic diseases (23 variants)
• not provided (20 variants)
• Verrucous venous malformation (1 variants)
• Verrucous hemangioma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP3K3 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		1	23		1	25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					15	15
Total	0	1	23	1	19

Variants in MAP3K3

This is a list of pathogenic ClinVar variants found in the MAP3K3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-63632650-G-A			Benign (Jun 19, 2021)
17-63632869-G-T			Benign (Jun 20, 2021)
17-63634724-A-G		not specified	Uncertain significance (May 27, 2022)
17-63634734-C-G		not specified	Uncertain significance (Jan 09, 2024)
17-63634742-A-C		not specified	Uncertain significance (Jan 23, 2024)
17-63634746-G-A		not specified	Uncertain significance (Sep 17, 2021)
17-63634769-T-C		not specified	Uncertain significance (Aug 23, 2021)
17-63634778-G-A		not specified	Uncertain significance (Nov 17, 2023)
17-63645770-AACAGCATGTC-A			Benign (Jun 19, 2021)
17-63652522-A-G			Benign (Jun 19, 2021)
17-63652635-T-A		not specified	Uncertain significance (Mar 23, 2022)
17-63657696-T-C			Benign (Jun 19, 2021)
17-63657837-T-C		not specified	Uncertain significance (Jul 19, 2022)
17-63657839-G-C		not specified	Uncertain significance (Jan 02, 2024)
17-63657973-C-T			Benign (Jun 20, 2021)
17-63666680-A-G			Benign (Jun 19, 2021)
17-63666979-C-T		not specified	Uncertain significance (Dec 09, 2023)
17-63667000-G-A		not specified	Uncertain significance (Feb 27, 2024)
17-63667000-G-T		not specified	Uncertain significance (Feb 14, 2023)
17-63667013-A-G		not specified	Uncertain significance (Sep 30, 2021)
17-63685671-G-C			Benign (Jun 19, 2021)
17-63685825-T-C			Benign (Nov 12, 2018)
17-63685848-A-G			Benign (Jun 19, 2021)
17-63688315-T-C			Benign (Jun 20, 2021)
17-63688530-A-C		MAP3K3-related disorder	Likely benign (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP3K3	protein_coding	protein_coding	ENST00000361357	17	73889

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.985	0.0147	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.04	293	409	0.716	0.0000256	4326
Missense in Polyphen		67	138	0.48552		1373
Synonymous	0.797	137	149	0.917	0.00000874	1261
Loss of Function	4.92	6	39.3	0.153	0.00000233	415

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000443	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:9006902}.
• Pathway: Neurotrophin signaling pathway - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);EGF-Core;IL-1 signaling pathway;TNF alpha Signaling Pathway;EBV LMP1 signaling;Structural Pathway of Interleukin 1 (IL-1);Angiopoietin Like Protein 8 Regulatory Pathway;MAPK Cascade;EGF-EGFR Signaling Pathway;Insulin Signaling;Signaling by Interleukins;mapkinase signaling pathway;Cytokine Signaling in Immune system;Interleukin-1 signaling;Immune System;IL-7 signaling;EGFR1;JAK STAT pathway and regulation;EPO signaling;TNFalpha;VEGF;TNF receptor signaling pathway ;Regulation of p38-alpha and p38-beta;p38 MAPK signaling pathway;IL1-mediated signaling events;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.240

Intolerance Scores

• loftool: 0.183
• rvis_EVS: -1.07
• rvis_percentile_EVS: 7.37

Haploinsufficiency Scores

• pHI: 0.798
• hipred: Y
• hipred_score: 0.786
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Map3k3
• Phenotype: hematopoietic system phenotype; 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); 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); embryo phenotype; immune system phenotype; muscle phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: MAPK cascade;activation of MAPKK activity;blood vessel development;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;intracellular signal transduction;positive regulation of I-kappaB kinase/NF-kappaB signaling;protein autophosphorylation;interleukin-1-mediated signaling pathway;positive regulation of cell proliferation in bone marrow;positive regulation of cell migration involved in sprouting angiogenesis;positive regulation of p38MAPK cascade;negative regulation of cellular senescence
• Cellular component: cytoplasm;cytosol
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;MAP kinase kinase kinase activity;protein binding;ATP binding;metal ion binding