MTREX

protein-coding

Mtr4 exosome RNA helicase, the group of Nuclear exosome targeting complex|Ski2 like RNA helicases

Gene summary

Enables ATP binding activity and RNA helicase activity. Involved in DNA damage response; RNA catabolic process; and maturation of 5.8S rRNA. Located in nuclear exosome (RNase complex) and nucleoplasm. Part of TRAMP complex and catalytic step 2 spliceosome. Biomarker of amyotrophic lateral sclerosis. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

KIAA0052
SKIV2L2

MANE transcript

NM_015360.5

Inheritance

—

ClinVar variants

U:124B:7

Top phenotype

Marfanoid habitus and intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr5:55,307,989-55,425,579

External References & Databases

Ensembl (ENSG00000039123)

Transcript & Mutation Effects

hg38 • Region Span ~117.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MTREX variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 105

not providedTotal: 5

Marfanoid habitus and intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015360.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	2 clinvar	2 clinvar	7
missense			109 clinvar	3 clinvar		112
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	124	5	2	131

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015360.5	RefSeq	NP_056175.3	27	MANE Select
ENST00000230640.10	Ensembl	ENSP00000230640.5	27	MANE Select
ENST00000505565.5	Ensembl	ENSP00000422125.1	3	Standard
ENST00000506750.5	Ensembl	ENSP00000425042.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mtrex	Danio rerio	Structure: eye Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

mtrex

Danio rerio

Structure: eye

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA degradation - Homo sapiens (human)

Biological Process

mRNA splicing, via spliceosome
maturation of 5.8S rRNA
rRNA processing
RNA catabolic process

Molecular Function

RNA binding
ATP-dependent RNA helicase activity
protein binding
ATP binding

Cellular Component

nuclear exosome (RNase complex)
exosome (RNase complex)
nucleus
nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000230640
Coding exons: 27
Length: 117822
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125746
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.06	345	546	0.632	0.0000281	6890
Missense (PolyPhen)		87	216.29	0.40224		2637
Synonymous	-1.25	198	177	1.12	0.00000894	1878
Loss of Function	5.69	12	59.3	0.202	0.00000318	766

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00016	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.00024	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of exosome targeting complexes. Subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that directs a subset of non-coding short-lived RNAs for exosomal degradation. Subunit of the trimeric poly(A) tail exosome targeting (PAXT) complex, a complex that directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor MTREX, which links to RNA-binding protein adapters (PubMed:27871484). Associated with the RNA exosome complex and involved in the 3'- processing of the 7S pre-RNA to the mature 5.8S rRNA (PubMed:17412707, PubMed:29107693). May be involved in pre-mRNA splicing. {ECO:0000269|PubMed:17412707, ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:29107693}.;

Recessive Scores

pRec: 0.156

Intolerance Scores

RVIS EVS: -1.15
RVIS percentile EVS: 6.23

Essentials

Essential (gene trap): E