MAP3K20
Basic information
Region (hg38): 2:173075435-173268015
Links
Phenotypes
GenCC
Source:
- 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
Clinical Genomic Database
Source:
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
- not provided (6 variants)
- Myopathy, centronuclear, 6, with fiber-type disproportion (1 variants)
- Split-foot malformation-mesoaxial polydactyly syndrome (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.
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 | 10 | 72 | 88 | |||
missense | 129 | 145 | ||||
nonsense | 7 | |||||
start loss | 0 | |||||
frameshift | 3 | |||||
inframe indel | 6 | |||||
splice donor/acceptor (+/-2bp) | 2 | |||||
splice region | 9 | 20 | 3 | 32 | ||
non coding | 12 | 58 | 31 | 101 | ||
Total | 7 | 2 | 159 | 138 | 46 |
Highest pathogenic variant AF is 0.000408
Variants in MAP3K20
This is a list of pathogenic ClinVar variants found in the MAP3K20 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
2-173091023-C-T | MAP3K20-related disorder | Likely benign (Apr 10, 2019) | ||
2-173091036-C-T | Uncertain significance (May 01, 2022) | |||
2-173091037-G-A | Likely benign (Nov 08, 2022) | |||
2-173091043-C-T | Uncertain significance (Jun 26, 2022) | |||
2-173091057-T-C | Inborn genetic diseases | Uncertain significance (Aug 13, 2022) | ||
2-173091094-C-T | Likely benign (Jul 26, 2022) | |||
2-173091097-C-T | Benign (Jan 15, 2024) | |||
2-173091102-G-C | Uncertain significance (Jun 23, 2022) | |||
2-173091133-A-G | Likely benign (Jan 11, 2022) | |||
2-173091154-G-A | Likely benign (Sep 08, 2023) | |||
2-173091186-A-G | Uncertain significance (Dec 23, 2021) | |||
2-173091197-T-A | Uncertain significance (Aug 04, 2022) | |||
2-173091203-C-T | Likely benign (Apr 17, 2023) | |||
2-173091208-T-C | Likely benign (Jun 06, 2023) | |||
2-173119323-C-G | Uncertain significance (May 28, 2024) | |||
2-173169786-C-T | Likely benign (Jan 30, 2024) | |||
2-173169801-A-G | Likely benign (Oct 06, 2023) | |||
2-173169819-T-C | Likely benign (Jun 20, 2022) | |||
2-173169852-T-C | Uncertain significance (Apr 06, 2022) | |||
2-173169879-T-C | Likely benign (Feb 21, 2023) | |||
2-173182836-T-A | Likely benign (Sep 27, 2021) | |||
2-173182837-C-T | Likely benign (Oct 20, 2023) | |||
2-173182840-T-C | Likely benign (Apr 22, 2021) | |||
2-173182842-C-G | Likely benign (Jun 20, 2022) | |||
2-173182851-T-C | Benign (Jun 01, 2024) |
GnomAD
Source:
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:
- 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
- loftool
- rvis_EVS
- 0.71
- rvis_percentile_EVS
- 85.82
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.706
- ghis
- 0.533
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- gene_indispensability_score
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