MECOM
MDS1 and EVI1 complex locus, the group of PR/SET domain family|Lysine methyltransferases|Zinc fingers C2H2-type
Basic information
Region (hg38): 3:169083499-169663775
Previous symbols: [ "MDS1", "EVI1" ]
Links
Phenotypes
GenCC
Source:
- radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (Definitive), mode of inheritance: AD
- radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome (Supportive), mode of inheritance: AD
- radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (Strong), mode of inheritance: AD
- radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (Strong), mode of inheritance: AD
- MECOM-associated syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 | AD | Allergy/Immunology/Infectious; Hematologic | The condition involves bone marrow failure, and awareness may allow prompt management of hematologic complications as well as complications related to susceptibility to infections; HSCT has been described | Allergy/Immunology/Infectious; Hematologic; Musculoskeletal | 20091385; 26581901 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (1325 variants)
- not_provided (445 variants)
- MECOM-related_disorder (46 variants)
- not_specified (46 variants)
- Radioulnar_synostosis_with_amegakaryocytic_thrombocytopenia_2 (33 variants)
- MECOM-associated_syndrome (12 variants)
- Radioulnar_synostosis (7 variants)
- Thrombocytopenia (3 variants)
- Dyskeratosis_congenita,_autosomal_dominant_1 (3 variants)
- Abnormal_bleeding (2 variants)
- Radioulnar_synostosis_with_amegakaryocytic_thrombocytopenia_1 (2 variants)
- Congenital_heart_disease (1 variants)
- Hereditary_cancer-predisposing_syndrome (1 variants)
- Premature_ovarian_failure (1 variants)
- Malignant_peritoneal_mesothelioma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MECOM gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004991.4. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 458 | 3 | 463 | ||
| missense | 7 | 15 | 989 | 34 | 2 | 1047 |
| nonsense | 5 | 3 | 3 | 11 | ||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 6 | 8 | ||
| Total | 17 | 19 | 1000 | 492 | 5 |
Highest pathogenic variant AF is 0.000014443806
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MECOM | protein_coding | protein_coding | ENST00000264674 | 16 | 580120 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 125726 | 0 | 7 | 125733 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.62 | 496 | 608 | 0.815 | 0.0000316 | 7461 |
| Missense in Polyphen | 177 | 255.63 | 0.69239 | 3150 | ||
| Synonymous | -1.28 | 252 | 227 | 1.11 | 0.0000131 | 2018 |
| Loss of Function | 6.02 | 2 | 46.1 | 0.0433 | 0.00000216 | 626 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000532 | 0.0000528 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Isoform 1: Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression. Oncogene which plays a role in development, cell proliferation and differentiation. May also play a role in apoptosis through regulation of the JNK and TGF-beta signaling. Involved in hematopoiesis. {ECO:0000269|PubMed:10856240, ECO:0000269|PubMed:11568182, ECO:0000269|PubMed:15897867, ECO:0000269|PubMed:16462766, ECO:0000269|PubMed:19767769, ECO:0000269|PubMed:9665135}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving EVI1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with RUNX1/AML1. {ECO:0000269|PubMed:8313895}.; DISEASE: Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (RUSAT2) [MIM:616738]: An autosomal dominant disease characterized by proximal fusion of the radius and ulna resulting in extremely limited pronation and supination of the forearm, and congenital thrombocytopenia that progresses to pancytopenia. {ECO:0000269|PubMed:26581901}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving MDS1 is found in a form of acute myeloid leukemia (AML). Translocation t(3;21) with AML1. {ECO:0000269|PubMed:8643684}.;
- Pathway
- Chronic myeloid leukemia - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);White fat cell differentiation;White fat cell differentiation;Signal Transduction;PKMTs methylate histone lysines;Chromatin modifying enzymes;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Chromatin organization;Intracellular signaling by second messengers
(Consensus)
Recessive Scores
- pRec
- 0.302
Intolerance Scores
- loftool
- rvis_EVS
- -0.99
- rvis_percentile_EVS
- 8.56
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.450
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Zebrafish Information Network
- Gene name
- mecom
- Affected structure
- ventral wall of dorsal aorta
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- regulation of transcription by RNA polymerase II;apoptotic process;cell differentiation;histone lysine methylation;negative regulation of programmed cell death;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;negative regulation of JNK cascade;regulation of cell cycle;hematopoietic stem cell proliferation
- Cellular component
- histone deacetylase complex;nucleus;nucleoplasm;cytosol;nuclear speck
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;histone-lysine N-methyltransferase activity;metal ion binding