MAP3K14

mitogen-activated protein kinase kinase kinase 14, the group of Mitogen-activated protein kinase kinase kinases

Basic information

Region (hg38): 17:45263118-45317029

Links

ENSG00000006062 ∙ NCBI:9020 ∙ OMIM:604655 ∙ HGNC:6853 ∙ Uniprot:Q99558 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• NIK deficiency (Supportive), mode of inheritance: AR
• NIK deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Primary immunodeficiency with multifaceted aberrant lymphoid immunity	AR	Allergy/Immunology/Infectious	Individuals have been described with recurrent bacterial, viral and Cryptosporidium infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described	Allergy/Immunology/Infectious	25406581

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAP3K14 gene.

• NIK deficiency (388 variants)
• not provided (22 variants)
• Inborn genetic diseases (6 variants)
• not specified (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP3K14 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			13	101	4	118
missense			170	9	4	183
nonsense			2			2
start loss						0
frameshift		1	4		1	6
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			17	8	2	27
non coding			6	44	7	57
Total	0	1	198	154	16

Variants in MAP3K14

This is a list of pathogenic ClinVar variants found in the MAP3K14 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-45264648-C-T		NIK deficiency	Likely benign (Jul 17, 2023)
17-45264654-C-T		NIK deficiency	Likely benign (Oct 24, 2023)
17-45264657-G-A		NIK deficiency	Uncertain significance (May 04, 2022)
17-45264660-A-G		NIK deficiency	Likely benign (Jun 20, 2022)
17-45264683-C-T		NIK deficiency	Uncertain significance (Jun 13, 2022)
17-45264684-G-A		NIK deficiency	Likely benign (Nov 03, 2023)
17-45264697-G-T		NIK deficiency	Uncertain significance (Dec 27, 2023)
17-45264701-C-T		NIK deficiency	Uncertain significance (Jul 05, 2018)
17-45264711-C-T		NIK deficiency	Likely benign (Oct 13, 2023)
17-45264720-G-A		NIK deficiency	Likely benign (Dec 12, 2022)
17-45264726-C-T		NIK deficiency	Likely benign (Dec 28, 2023)
17-45264738-C-T		NIK deficiency	Likely benign (Oct 13, 2023)
17-45264751-C-T		NIK deficiency	Uncertain significance (Aug 27, 2021)
17-45264752-G-A		NIK deficiency	Uncertain significance (Apr 24, 2023)
17-45264753-A-T		NIK deficiency	Likely benign (Sep 01, 2023)
17-45264758-G-A		NIK deficiency	Uncertain significance (Aug 21, 2022)
17-45264765-G-A		NIK deficiency	Likely benign (Jan 02, 2024)
17-45264774-G-C		NIK deficiency • not specified	Benign (Feb 01, 2024)
17-45264780-G-A		NIK deficiency	Likely benign (Jan 15, 2023)
17-45264786-G-A		NIK deficiency	Likely benign (Jul 31, 2023)
17-45264790-G-C		NIK deficiency	Uncertain significance (Jun 14, 2022)
17-45265146-G-A		NIK deficiency	Benign (Jan 25, 2024)
17-45265149-C-T		NIK deficiency	Likely benign (Jan 21, 2023)
17-45265152-G-C		NIK deficiency	Likely benign (Sep 17, 2022)
17-45265156-C-T		NIK deficiency	Likely benign (Jul 18, 2023)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non- canonical pathway. Could act in a receptor-selective manner. {ECO:0000269|PubMed:15084608}.
• Pathway: T cell receptor signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Apoptosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Intestinal immune network for IgA production - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Osteopontin Signaling;MicroRNAs in cardiomyocyte hypertrophy;Apoptosis Modulation and Signaling;IL-1 signaling pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;IL17 signaling pathway;TNF alpha Signaling Pathway;EBV LMP1 signaling;Structural Pathway of Interleukin 1 (IL-1);Cardiac Hypertrophic Response;MAPK Signaling Pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;Angiopoietin Like Protein 8 Regulatory Pathway;Insulin Signaling;T-Cell antigen Receptor (TCR) Signaling Pathway;tnfr2 signaling pathway;induction of apoptosis through dr3 and dr4/5 death receptors;hiv-1 nef: negative effector of fas and tnf;toll-like receptor pathway;mapkinase signaling pathway;TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway;NIK-->noncanonical NF-kB signaling;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;CD28 dependent PI3K/Akt signaling;CD28 co-stimulation;Costimulation by the CD28 family;Dectin-1 mediated noncanonical NF-kB signaling;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Innate Immune System;Immune System;Adaptive Immune System;IL1;IL-7 signaling;EGFR1;JAK STAT pathway and regulation;PDGF;EPO signaling;TNFalpha;VEGF;Osteopontin-mediated events;HIV-1 Nef: Negative effector of Fas and TNF-alpha;CD40/CD40L signaling;TCR signaling in naïve CD8+ T cells;Alternative NF-kappaB pathway;TCR signaling in naïve CD4+ T cells (Consensus)

Recessive Scores

• pRec: 0.575

Haploinsufficiency Scores

• pHI: 0.188

Essentials

• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Mouse Genome Informatics

• Gene name: Map3k14
• 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); hematopoietic system phenotype; liver/biliary system phenotype; respiratory system phenotype; immune system phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: MAPK cascade;activation of MAPKK activity;immune response;I-kappaB kinase/NF-kappaB signaling;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;tumor necrosis factor-mediated signaling pathway;NIK/NF-kappaB signaling;positive regulation of I-kappaB kinase/NF-kappaB signaling;defense response to virus;cellular response to mechanical stimulus
• Cellular component: fibrillar center;nucleus;cytoplasm;cytosol;intracellular membrane-bounded organelle
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;NF-kappaB-inducing kinase activity;MAP kinase kinase kinase activity;protein binding;ATP binding;kinase activity