MTX2

metaxin 2, the group of Metaxins

Basic information

Region (hg38): 2:176269395-176338025

Links

ENSG00000128654 ∙ NCBI:10651 ∙ OMIM:608555 ∙ HGNC:7506 ∙ Uniprot:O75431 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mandibuloacral dysplasia (Supportive), mode of inheritance: AR
• mandibuloacral dysplasia progeroid syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mandibuloacral dysplasia progeroid syndrome	AR	Allergy/Immunology/Infectious; Cardiovascular	Among other findings, individuals may have early-onset respiratory infections, and awareness may allow prompt diagnosis and management; Cardiovascular manifestations, including cardiomyopathy and valvular anomalies, have been described, and awareness may allow prompt diagnosis and management	Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic	32917887

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MTX2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTX2 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					1	1
missense			12			12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding						0
Total	0	1	12	0	1

Variants in MTX2

This is a list of pathogenic ClinVar variants found in the MTX2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-176269631-T-A		Progeroid mandibuloacral dysplasia • Mandibuloacral dysplasia progeroid syndrome	Pathogenic (Dec 16, 2020)
2-176297869-G-A		not specified	Uncertain significance (Sep 29, 2023)
2-176297891-T-C		not specified	Uncertain significance (Aug 26, 2022)
2-176297897-T-C		Mandibuloacral dysplasia progeroid syndrome	Likely pathogenic (-)
2-176323464-GGTAA-G		Progeroid mandibuloacral dysplasia • Mandibuloacral dysplasia progeroid syndrome	Pathogenic (Jan 04, 2021)
2-176326839-A-T		not specified	Uncertain significance (Nov 15, 2021)
2-176328298-TTC-T		10 conditions • Mandibuloacral dysplasia progeroid syndrome	Pathogenic (Dec 16, 2020)
2-176328354-A-C		not specified	Uncertain significance (Apr 01, 2024)
2-176328878-A-G		not specified	Uncertain significance (Aug 22, 2023)
2-176328904-G-A		not specified	Uncertain significance (Jul 06, 2021)
2-176329356-C-G		not specified	Uncertain significance (Mar 16, 2022)
2-176330583-G-C		Progeroid mandibuloacral dysplasia • Mandibuloacral dysplasia progeroid syndrome	Pathogenic (Jan 04, 2021)
2-176330613-A-G			Benign (Jul 01, 2022)
2-176330620-T-C		not specified	Uncertain significance (Jun 13, 2023)
2-176330641-C-T		not specified	Uncertain significance (Mar 16, 2024)
2-176330642-CG-C		Progeroid mandibuloacral dysplasia • Mandibuloacral dysplasia progeroid syndrome	Pathogenic (Dec 16, 2020)
2-176337534-C-T		not specified	Uncertain significance (Apr 09, 2024)
2-176337542-A-G		not specified	Uncertain significance (Nov 27, 2023)
2-176337583-A-C		not specified	Uncertain significance (Jan 16, 2024)
2-176337593-A-G		not specified	Uncertain significance (Jul 20, 2021)
2-176337638-G-C		not specified	Uncertain significance (Aug 21, 2023)
2-176337642-G-A		not specified	Uncertain significance (Aug 13, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTX2	protein_coding	protein_coding	ENST00000249442	10	68631

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0192	0.977	125514	0	17	125531	0.0000677

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.838	104	131	0.794	0.00000606	1707
Missense in Polyphen		23	31.609	0.72763		438
Synonymous	-1.86	60	44.2	1.36	0.00000209	469
Loss of Function	2.55	6	17.5	0.343	7.41e-7	215

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000234	0.000234
Ashkenazi Jewish	0.000101	0.0000994
East Asian	0.0000550	0.0000544
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000465	0.0000441
Middle Eastern	0.0000550	0.0000544
South Asian	0.0000404	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in transport of proteins into the mitochondrion. {ECO:0000269|PubMed:10381257}.
• Pathway: Metabolism of proteins;Mitochondrial protein import (Consensus)

Recessive Scores

• pRec: 0.115

Intolerance Scores

• loftool: 0.609
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.26

Haploinsufficiency Scores

• pHI: 0.192
• hipred: Y
• hipred_score: 0.543
• ghis: 0.586

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.427

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mtx2

Gene ontology

• Biological process: mitochondrial transport;protein transport
• Cellular component: mitochondrial sorting and assembly machinery complex;nucleolus;mitochondrion;mitochondrial outer membrane
• Molecular function: protein binding