MAP3K20

mitogen-activated protein kinase kinase kinase 20, the group of Mitogen-activated protein kinase kinase kinases

Basic information

Region (hg38): 2:173075435-173268015

Links

ENSG00000091436 ∙ NCBI:51776 ∙ OMIM:609479 ∙ HGNC:17797 ∙ Uniprot:Q9NYL2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital fiber-type disproportion myopathy (Supportive), mode of inheritance: AD
• split-foot malformation-mesoaxial polydactyly syndrome (Limited), mode of inheritance: AR
• myopathy, centronuclear, 6, with fiber-type disproportion (Moderate), mode of inheritance: AR
• myopathy, centronuclear, 6, with fiber-type disproportion (Moderate), mode of inheritance: AR
• split-foot malformation-mesoaxial polydactyly syndrome (Limited), mode of inheritance: AR
• split hand-foot malformation (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Split-foot malformation with mesoaxial polydactyly; Myopathy, centronuclear 6, with fiber-type disproportion	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	26755636; 27816943

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAP3K20 gene.

• not_provided (382 variants)
• MAP3K20-related_disorder (8 variants)
• Inborn_genetic_diseases (5 variants)
• Split-foot_malformation-mesoaxial_polydactyly_syndrome (5 variants)
• Myopathy,_centronuclear,_6,_with_fiber-type_disproportion (3 variants)
• not_specified (2 variants)
• See_cases (1 variants)
• Centronuclear_myopathy (1 variants)
• Split_hand-foot_malformation_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAP3K20 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016653.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				97	2	99
missense	1		130	11	7	149
nonsense	5	1	3			9
start loss						0
frameshift	4	1				5
splice donor/acceptor (+/-2bp)		1	1			2
Total	10	3	134	108	9

Highest pathogenic variant AF is 0.00008993431

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAP3K20	protein_coding	protein_coding	ENST00000375213	19	192576

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.42e-9	1.00	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	335	422	0.794	0.0000212	5262
Missense in Polyphen		111	172.62	0.64303		2201
Synonymous	-0.0154	150	150	1.00	0.00000799	1453
Loss of Function	3.26	21	44.4	0.473	0.00000211	550

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00195	0.00187
Ashkenazi Jewish	0.00	0.00
East Asian	0.000168	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000161	0.000158
Middle Eastern	0.000168	0.000163
South Asian	0.000267	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2 (PubMed:10924358, PubMed:11836244, PubMed:15342622, PubMed:21224381). Involved in limb development (PubMed:26755636). {ECO:0000269|PubMed:10924358, ECO:0000269|PubMed:11836244, ECO:0000269|PubMed:15342622, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:26755636}.
• Disease: DISEASE: Myopathy, centronuclear, 6, with fiber-type disproportion (CNM6) [MIM:617760]: A form of centronuclear myopathy, a congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. CNM6 is an autosomal recessive, slowly progressive form with onset in infancy or early childhood. {ECO:0000269|PubMed:27816943}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: MAPK signaling pathway - Homo sapiens (human);EGF-Core;MAPK Signaling Pathway;Signaling mediated by p38-gamma and p38-delta (Consensus)

Intolerance Scores

• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.82

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.706
• ghis: 0.533

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Map3k20
• Phenotype: limbs/digits/tail phenotype; skeleton phenotype; embryo 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); growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: DNA damage checkpoint;activation of MAPKK activity;protein phosphorylation;cytoskeleton organization;cell cycle arrest;mitotic cell cycle checkpoint;activation of JUN kinase activity;cell death;cell population proliferation;cell differentiation;embryonic digit morphogenesis;positive regulation of apoptotic process;stress-activated MAPK cascade;limb development;cellular response to gamma radiation
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: magnesium ion binding;RNA binding;protein serine/threonine kinase activity;MAP kinase kinase kinase activity;protein binding;ATP binding