REXO4

protein-coding

REX4 homolog, 3'-5' exonuclease, the group of Exonucleases

Gene summary

Enables DNA binding activity and nuclease activity. Involved in DNA catabolic process and DNA repair. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

XPMC2H

MANE transcript

NM_020385.4

Inheritance

—

ClinVar variants

U:75B:6

Top phenotype

Recurrent spontaneous abortion

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr9:133,406,059-133,418,096

External References & Databases

Ensembl (ENSG00000148300)

Transcript & Mutation Effects

hg38 • Region Span ~12.0 kb

Loading mutation effect viewer...

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 REXO4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 2

Recurrent spontaneous abortionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020385.4. 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			1 clinvar	1 clinvar		2
missense			69 clinvar	5 clinvar		74
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	75	6	0	81

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020385.4	RefSeq	NP_065118.2	8	MANE Select
ENST00000371942.8	Ensembl	ENSP00000361010.3	8	MANE Select
NM_001279349.2	RefSeq	NP_001266278.1	6	Standard
NM_001279350.2	RefSeq	NP_001266279.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated
rRNA processing
nucleic acid phosphodiester bond hydrolysis

Molecular Function

DNA-binding transcription factor activity
RNA binding
3'-5' exonuclease activity

Cellular Component

nucleus
nucleolus
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371942
Coding exons: 8
Length: 11979
Individuals with no LoFs: 125589
Homozygous LoFs: 1
Heterozygous LoFs: 158
Defined: 125748
p: 0.000632

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.107	246	251	0.981	0.0000145	2764
Missense (PolyPhen)		52	69.182	0.75164		758
Synonymous	1.11	87	101	0.860	0.00000682	813
Loss of Function	1.29	12	17.9	0.671	8.58e-7	222

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0064	0.0064	notable
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.00053	0.00052	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0998

Intolerance Scores

LoFtool: 0.655
RVIS EVS: 0.38
RVIS percentile EVS: 75.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.633

Gene Damage Prediction

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