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

ENSG00000085276 ∙ NCBI:2122 ∙ OMIM:165215 ∙ HGNC:3498 ∙ Uniprot:Q03112 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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
• MECOM-associated syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the MECOM gene.

• not provided (4 variants)
• Hereditary cancer-predisposing syndrome (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.

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				84	10	94
missense	2	1	193	12	5	213
nonsense	2	2	1			5
start loss			1			1
frameshift	1					1
inframe indel			2			2
splice donor/acceptor (+/-2bp)			3			3
splice region		1	5	13	1	20
non coding		3	4	17	8	32
Total	5	6	204	113	23

Highest pathogenic variant AF is 0.00000658

Variants in MECOM

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

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

Position	Type	Phenotype	Significance	ClinVar
3-169084908-G-T		MECOM-related disorder	Likely benign (Jan 21, 2021)
3-169084912-T-C			Likely benign (Jan 01, 2024)
3-169084914-C-T			Uncertain significance (Mar 01, 2023)
3-169084946-G-A		not specified	Uncertain significance (Aug 27, 2021)
3-169084948-C-T			Likely benign (Jul 09, 2023)
3-169084949-G-A			Likely benign (Jan 22, 2024)
3-169084949-G-T		not specified	Uncertain significance (Jun 10, 2020)
3-169084967-T-A			Uncertain significance (Feb 11, 2023)
3-169084974-C-A		Inborn genetic diseases	Uncertain significance (Nov 13, 2023)
3-169084974-C-G		Inborn genetic diseases	Uncertain significance (Dec 26, 2023)
3-169084974-C-T			Uncertain significance (Oct 24, 2022)
3-169084976-T-C			Uncertain significance (Dec 15, 2022)
3-169084993-T-G		not specified	Benign (Aug 09, 2023)
3-169084994-G-A			Uncertain significance (Mar 27, 2022)
3-169085010-C-G			Uncertain significance (Nov 17, 2023)
3-169085028-G-T		Inborn genetic diseases	Uncertain significance (Dec 09, 2023)
3-169085028-GC-TA			Uncertain significance (Sep 28, 2022)
3-169085038-A-G			Likely benign (Jan 20, 2024)
3-169085044-C-G			Uncertain significance (May 15, 2023)
3-169085056-G-A			Likely benign (Sep 27, 2022)
3-169088988-G-C			Likely benign (Jul 27, 2022)
3-169088992-A-C			Likely benign (Jun 13, 2018)
3-169088993-T-G			Likely benign (Mar 27, 2023)
3-169088997-T-C		MECOM-related disorder	Uncertain significance (Jan 11, 2024)
3-169089001-T-C			Uncertain significance (Dec 26, 2023)

GnomAD

Source: gnomAD

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
1.00	0.00000155	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: dbNSFP

• 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

• rvis_EVS: -0.99
• rvis_percentile_EVS: 8.56

Haploinsufficiency Scores

• pHI: 0.480
• hipred: Y
• hipred_score: 0.682
• ghis: 0.481

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

Mouse Genome Informatics

• Gene name: Mecom
• Phenotype: immune system phenotype; skeleton phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail 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); normal phenotype; reproductive system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region 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)

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