MTX2

Chr 2AR

metaxin 2

Also known as: MDPS, metaxin-2

NCBI Gene: 10651 ENSG00000128654 UniProt: O75431 OMIM: 608555

The protein encoded by this gene is highly similar to the metaxin 2 protein from mouse, which has been shown to interact with the mitochondrial membrane protein metaxin 1. Because of this similarity, it is thought that the encoded protein is peripherally associated with the cytosolic face of the outer mitochondrial membrane, and that it is involved in the import of proteins into the mitochondrion. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Jun 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

GOFmechanismARLOEUF 0.681 OMIM phenotype

Clinical Summary— MTX2

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Gene-Disease Validity (ClinGen)

mandibuloacral dysplasia progeroid syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 30 VUS of 61 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.019

Z-score 2.55

OE 0.34 (0.19–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.84Z-score

OE missense 0.79 (0.68–0.93)

104 obs / 131.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.19–0.68)

0≤0.351.4

Missense OE?0.79 (0.68–0.93)

0≤0.61.4

Synonymous OE?1.36

0≤1.21.6

LoF obs/exp: 6 / 17.5Missense obs/exp: 104 / 131.0Syn Z: -1.86

This gene — mechanism propensity

0.5967th %ile

GOF

0.6832th %ile

LOF

0.2484th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic2

VUS30

Benign1

Pathogenic

Likely Pathogenic

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	1	0	0	7
Likely Pathogenic	2	0	0	0	2
VUS	0	29	1	0	30
Likely Benign	0	0	0	0	0
Benign	0	0	0	1	1
Total	8	30	1	1	40

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

29 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap MTX2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →