REXO2

Summary

REXO2 (RNA exonuclease 2, HGNC:17851) is a protein-coding gene on chromosome 11q23.2, encoding Oligoribonuclease, mitochondrial (Q9Y3B8). 3’-to-5’exoribonuclease that preferentially degrades DNA and RNA oligonucleotides composed of only two nucleotides. It is a selective cancer dependency (DepMap: 18.9% of cell lines).

This gene encodes a 3’-to-5’ exonuclease specific for small (primarily 5 nucleotides or less in length) single-stranded RNA and DNA oligomers. This protein may have a role in DNA repair, replication, and recombination, and in RNA processing and degradation. It may also be involved in resistance of human cells to UV-C-induced cell death through its role in the DNA repair process.

Source: NCBI Gene 25996 — RefSeq curated summary.

At a glance

• Gene–disease (curated): type 1 interferonopathy of childhood (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 31 total
• Cancer dependency (DepMap): dependent in 18.9% of screened cell lines
• MANE Select transcript: NM_015523

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17851
Approved symbol	REXO2
Name	RNA exonuclease 2
Location	11q23.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP566E144, SFN, CGI-114
Ensembl gene	ENSG00000076043
Ensembl biotype	protein_coding
OMIM	607149
Entrez	25996

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 15 protein_coding, 6 retained_intron, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000265881, ENST00000538198, ENST00000538403, ENST00000538791, ENST00000539119, ENST00000539275, ENST00000539333, ENST00000539754, ENST00000539788, ENST00000540492, ENST00000541703, ENST00000542186, ENST00000543131, ENST00000543243, ENST00000544010, ENST00000544196, ENST00000544507, ENST00000544827, ENST00000546316, ENST00000866988, ENST00000866989, ENST00000928174, ENST00000928175, ENST00000928176, ENST00000928177, ENST00000928178, ENST00000928179, ENST00000928180

RefSeq mRNA: 1 — MANE Select: NM_015523 NM_015523

CCDS: CCDS8371

Canonical transcript exons

ENST00000265881 — 7 exons

Exon	Start	End
ENSE00000996420	114444541	114444652
ENSE00000996423	114443856	114443933
ENSE00003527940	114447826	114447879
ENSE00003569238	114445979	114446087
ENSE00003617172	114449846	114450279
ENSE00003632991	114440656	114440739
ENSE00003841217	114439467	114439675

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.3344 / max 709.1135, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116817	73.9465	1823
116818	6.2527	1469
116815	1.0724	618
116816	0.8218	518
116814	0.2410	102

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.74	gold quality
oocyte	CL:0000023	99.71	gold quality
decidua	UBERON:0002450	99.34	gold quality
calcaneal tendon	UBERON:0003701	99.14	gold quality
stromal cell of endometrium	CL:0002255	98.99	gold quality
heart right ventricle	UBERON:0002080	98.92	gold quality
smooth muscle tissue	UBERON:0001135	98.74	gold quality
vena cava	UBERON:0004087	98.63	gold quality
saphenous vein	UBERON:0007318	98.52	gold quality
parotid gland	UBERON:0001831	98.49	gold quality
nephron tubule	UBERON:0001231	98.45	gold quality
left ventricle myocardium	UBERON:0006566	98.45	gold quality
tendon	UBERON:0000043	98.44	gold quality
amniotic fluid	UBERON:0000173	98.44	gold quality
left ovary	UBERON:0002119	98.40	gold quality
myometrium	UBERON:0001296	98.36	gold quality
cardiac ventricle	UBERON:0002082	98.30	gold quality
heart left ventricle	UBERON:0002084	98.29	gold quality
endocervix	UBERON:0000458	98.23	gold quality
right ovary	UBERON:0002118	98.20	gold quality
ovary	UBERON:0000992	98.19	gold quality
body of uterus	UBERON:0009853	98.18	gold quality
tibia	UBERON:0000979	98.17	gold quality
gingiva	UBERON:0001828	98.17	gold quality
gingival epithelium	UBERON:0001949	98.15	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.13	gold quality
ectocervix	UBERON:0012249	98.10	gold quality
saliva-secreting gland	UBERON:0001044	98.01	gold quality
trabecular bone tissue	UBERON:0002483	98.01	gold quality
heart	UBERON:0000948	98.00	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	571.36
E-HCAD-4	yes	153.38
E-HCAD-6	yes	60.80
E-HCAD-13	yes	25.02
E-CURD-122	yes	23.07
E-MTAB-6701	yes	15.41
E-GEOD-98556	no	85.23
E-MTAB-10287	no	39.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting REXO2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-6776-3P	98.38	66.34	655
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-6836-3P	97.08	64.99	712
HSA-MIR-631	97.05	66.93	602
HSA-MIR-346	97.01	66.97	662
HSA-MIR-632	96.08	67.17	798
HSA-MIR-4661-5P	93.34	67.13	400

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• SFN expression is involved in resistance of RSa cells to UV-C-induced cell death through the roles it plays in the DNA repair process (PMID:15362935)
• The expression in E. coli of orn and homologues from Mycobacterium smegmatis and human, and large-scale purification of the three enzymes, is reported. (PMID:18023590)
• REXO2 is an oligoribonuclease active in human mitochondria and present both in cytosolic and mitochondrial fractions. (PMID:23741365)
• Loss of 14-3-3sigma sensitizes cells to UVB. After a transient cell cycle arrest, 14-3-3sigma-deficient cells die by undergoing mitotic catastrophe. (PMID:24102700)
• CBY1 downregulation in CML arises from reduced protein stability upon binding to 14-3-3sigma adapter protein. The ubiquitin proteasome system UPS participates in reducing stability of CBY1 bound with 14-3-3sigma through enhanced SUMOylation. (PMID:26147002)
• results demonstrate that 14-3-3sigma induces cisplatin resistance in esophageal squamous cell carcinoma cells (PMID:26346170)
• This study provides the molecular basis for human Rexo2, showing how it binds and degrades nanoRNA into nucleoside monophosphates and plays a crucial role in RNA salvage pathways in mammalian mitochondria. (PMID:30926754)
• Efficient RNA turnover by REXO2 is thus required to maintain promoter specificity and proper regulation of transcription in mammalian mitochondria. (PMID:31588022)
• Germline variant in REXO2 is a novel candidate gene in familial pheochromocytoma. (PMID:32354376)
• Human REXO2 controls short mitochondrial RNAs generated by mtRNA processing and decay machinery to prevent accumulation of double-stranded RNA. (PMID:32365187)
• RUNX1 and REXO2 are associated with the heterogeneity and prognosis of IDH wild type lower grade glioma. (PMID:34088969)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	smfn	ENSDARG00000009806
mus_musculus	Rexo2	ENSMUSG00000032026
rattus_norvegicus	Rexo2	ENSRNOG00000018939
drosophila_melanogaster	CG10214	FBGN0039115
caenorhabditis_elegans		WBGENE00007429

Protein

Protein identifiers

Oligoribonuclease, mitochondrial — Q9Y3B8 (reviewed: Q9Y3B8)

Alternative names: RNA exonuclease 2 homolog, Small fragment nuclease

All UniProt accessions (10): Q9Y3B8, F5GYG5, F5H6P8, F5H784, F5H7P1, H0YF66, H0YG37, H0YG54, H0YGR4, Q9BTR4

UniProt curated annotations — full annotation on UniProt →

Function. 3’-to-5’exoribonuclease that preferentially degrades DNA and RNA oligonucleotides composed of only two nucleotides. Binds and degrades longer oligonucleotides with a lower affinity. Plays dual roles in mitochondria, scavenging nanoRNAs (small RNA oligonucleotides of <5 nucleotides) that are produced by the degradosome and clearing short RNAs that are generated by RNA processing. Essential for correct initiation of mitochondrial transcription, degrading mitochondrial RNA dinucleotides to prevent RNA-primed transcription at non-canonical sites in the mitochondrial genome. Essential for embryonic development. 3’-to-5’exoribonuclease that preferentially degrades DNA and RNA oligonucleotides composed of only two nucleotides.

Subunit / interactions. Homodimer. Homotetramer.

Subcellular location. Mitochondrion intermembrane space. Mitochondrion matrix. Mitochondrion. Cytoplasm. Nucleus Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in the heart and at lower levels in the lymph nodes, brain, lung, liver, spleen and thymus.

Activity regulation. Inhibited by adenosine 3’,5’-bisphosphate.

Similarity. Belongs to the oligoribonuclease family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y3B8-1	1, Sfn-alpha	yes
Q9Y3B8-2	2
Q9Y3B8-3	3, Sfn

RefSeq proteins (1): NP_056338* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR013520	Ribonucl_H	Domain
IPR022894	Oligoribonuclease	Family
IPR036397	RNaseH_sf	Homologous_superfamily

Pfam: PF00929

Enzyme classification (BRENDA):

• EC 3.1.13.3 — oligonucleotidase (BRENDA: 16 organisms, 73 substrates, 21 inhibitors, 15 Km, 11 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5’-P-NITROPHENYL-TMP	0.27–1.9	6
(AP)2	0.25–0.66	2
(AP)2A	2.47	1
(AP)3	0.05	1
(AP)3A	3.03	1
(AP)4	0.021	1
(AP)6	0.017	1
5’-PHOSPHOGUANYLYL-(3’,5’)-GUANOSINE	0.0121	1
P-NITROPHENYL URIDINE 5’-MONOPHOSPHATE	0.41	1

UniProt features (50 total): mutagenesis site 14, helix 11, strand 5, binding site 5, site 3, modified residue 3, splice variant 2, turn 2, transit peptide 1, chain 1, domain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
6N6J	X-RAY DIFFRACTION	1.32
6N6K	X-RAY DIFFRACTION	1.42
6N6I	X-RAY DIFFRACTION	1.43
6J80	X-RAY DIFFRACTION	1.81
6RCL	X-RAY DIFFRACTION	1.97
6RCI	X-RAY DIFFRACTION	2
6J7Z	X-RAY DIFFRACTION	2
6J7Y	X-RAY DIFFRACTION	2.2
6RCN	X-RAY DIFFRACTION	2.25
6STY	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3B8-F1	89.32	0.75

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 96 (important for dinucleotide binding); 164 (important for dinucleotide binding); 194; 53 (important for dinucleotide binding)

Ligand- & substrate-binding residues (5): 47; 47; 49; 147; 199

Post-translational modifications (3): 92, 122, 173

Mutagenesis-validated functional residues (14):

Position	Phenotype
47	loss of 3’-to-5’exoribonuclease activity.
49	loss of 3’-to-5’exoribonuclease activity.
53	loss of 3’-to-5’exoribonuclease activity.
96	loss of 3’-to-5’exoribonuclease activity.
146	no effect on 3’-to-5’exoribonuclease activity.
147	loss of 3’-to-5’exoribonuclease activity.
164	loss of 3’-to-5’exoribonuclease activity.
178	disruption of homodimerization and loss of 3’-to-5’exoribonuclease activity; when associated with r-179 or a-179.
179	disruption of homodimerization and loss of 3’-to-5’exoribonuclease activity; when associated with a-178 or a-215.
179	disruption of homodimerization and loss of 3’-to-5’exoribonuclease activity; when associated with a-178.
194	loss of 3’-to-5’exoribonuclease activity.
199	loss of 3’-to-5’exoribonuclease activity.
215	disruption of homodimerization and loss of 3’-to-5’exoribonuclease activity; when associated with a-179.
136	50% reduction in 3’-to-5’exoribonuclease activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9836573	Mitochondrial RNA degradation

MSigDB gene sets: 653 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GCACCTT_MIR18A_MIR18B, SHEPARD_BMYB_MORPHOLINO_UP, AP1_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOMF_RNA_NUCLEASE_ACTIVITY, CCAWYNNGAAR_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT

GO Biological Process (4): nucleobase-containing compound metabolic process (GO:0006139), nucleotide metabolic process (GO:0009117), mitochondrial RNA surveillance (GO:2000827), DNA metabolic process (GO:0006259)

GO Molecular Function (9): 3’-5’-RNA exonuclease activity (GO:0000175), magnesium ion binding (GO:0000287), nucleic acid binding (GO:0003676), 3’-5’-DNA exonuclease activity (GO:0008296), 3’-5’ exonuclease activity (GO:0008408), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759), focal adhesion (GO:0005925)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
3’-5’ exonuclease activity	2
intracellular membrane-bounded organelle	2
primary metabolic process	1
nucleoside phosphate metabolic process	1
mitochondrial RNA catabolic process	1
cytoplasmic RNA surveillance	1
nucleic acid metabolic process	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
metal ion binding	1
binding	1
DNA exonuclease activity, producing 5’-phosphomonoesters	1
exonuclease activity	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
mitochondrial envelope	1
organelle envelope lumen	1
intracellular organelle lumen	1
cell-substrate junction	1

Protein interactions and networks

STRING

1496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
REXO2	REXO4	Q9GZR2	827
REXO2	EXO1	Q9UQ84	822
REXO2	PNPT1	Q8TCS8	743
REXO2	SUPV3L1	Q8IYB8	603
REXO2	EXOSC10	Q01780	579
REXO2	ELAC2	Q9BQ52	572
REXO2	YBEY	P58557	543
REXO2	DEDD	O75618	541
REXO2	REXO5	Q96IC2	502
REXO2	NANOG	Q9H9S0	492
REXO2	ELAC1	Q9H777	492
REXO2	LACTB2	Q53H82	460
REXO2	DIS3	Q9Y2L1	436
REXO2	RNASEH1	O60930	428
REXO2	REXO1	Q8N1G1	426

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MCC	REXO2	psi-mi:“MI:0915”(physical association)	0.000
REXO2	EIF1B	psi-mi:“MI:0915”(physical association)	0.000
ATG5	REXO2	psi-mi:“MI:0915”(physical association)	0.000
TRAF6	REXO2	psi-mi:“MI:0915”(physical association)	0.000
MPG	REXO2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (45): HSPD1 (Co-fractionation), MYL6 (Co-fractionation), PMS2 (Co-fractionation), REXO2 (Co-fractionation), SCLY (Co-fractionation), SEPHS1 (Co-fractionation), TXNDC17 (Co-fractionation), TYMS (Co-fractionation), REXO2 (Negative Genetic), REXO2 (Negative Genetic), REXO2 (Positive Genetic), TIMELESS (Negative Genetic), UBA2 (Positive Genetic), XRN2 (Negative Genetic), REXO2 (Co-fractionation)

ESM2 similar proteins: A0JMG1, A2VE52, D3K5L7, E0CZ16, E1C6Q1, E2R222, F1LZ52, F1LZF0, F1MBP6, O13016, O35345, O43791, O60684, O95164, O95198, O95544, P35815, P36993, P54797, P58058, P63143, P63144, Q0IHH9, Q0V7M0, Q0VCW1, Q15645, Q28528, Q28F89, Q2M2N2, Q2TA46, Q3UA06, Q4PJK1, Q5BL35, Q5NVK7, Q5RBV0, Q5REP9, Q5U1X1, Q5XHZ9, Q6GR09, Q6IQ16

Diamond homologs: A0K5Q4, A0KNT4, A0PU74, A0QDA8, A1K5N0, A1KLK6, A1SA28, A1TND9, A1U4D2, A1UJ99, A1V6I4, A1WB43, A1WTK7, A2S4M9, A2VE52, A3MHS8, A3NBZ6, A3NXT2, A3Q2P5, A3QAD3, A4JCK6, A4QGM5, A4SJD0, A4VR15, A4W5Q6, A5EY84, A5U5K8, A6TH79, A6VD64, A7MZ48, A7ZV33, A8A7Q9, A8AMN6, A8G8U2, O07708, P0A784, P0A785, P57665, P57666, P57667

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

31 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1618 predictions. Top by Δscore:

Variant	Effect	Δscore
11:114440737:G:GT	donor_gain	1.0000
11:114440737:GAA:G	donor_gain	1.0000
11:114440738:AA:A	donor_gain	1.0000
11:114440738:AAGT:A	donor_loss	1.0000
11:114440739:AGT:A	donor_loss	1.0000
11:114440740:G:GG	donor_gain	1.0000
11:114440741:T:A	donor_loss	1.0000
11:114449843:TAGG:T	acceptor_loss	1.0000
11:114449844:A:AG	acceptor_gain	1.0000
11:114449844:AG:A	acceptor_gain	1.0000
11:114449845:G:A	acceptor_loss	1.0000
11:114449845:G:GG	acceptor_gain	1.0000
11:114449845:GG:G	acceptor_gain	1.0000
11:114439672:GGAG:G	donor_gain	0.9900
11:114439673:GAGG:G	donor_gain	0.9900
11:114439676:GT:G	donor_loss	0.9900
11:114440651:TGCA:T	acceptor_loss	0.9900
11:114440652:GCA:G	acceptor_loss	0.9900
11:114440653:CA:C	acceptor_loss	0.9900
11:114440654:A:AG	acceptor_gain	0.9900
11:114440654:A:AT	acceptor_loss	0.9900
11:114440655:G:GA	acceptor_gain	0.9900
11:114440655:GAT:G	acceptor_gain	0.9900
11:114440735:CTGAA:C	donor_gain	0.9900
11:114440736:TGAA:T	donor_gain	0.9900
11:114440740:GTACG:G	donor_loss	0.9900
11:114443854:AG:A	acceptor_gain	0.9900
11:114443855:GG:G	acceptor_gain	0.9900
11:114449214:G:GT	donor_gain	0.9900
11:114449845:GGGCA:G	acceptor_gain	0.9900

AlphaMissense

1581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:114439661:T:A	W45R	0.998
11:114439661:T:C	W45R	0.998
11:114446005:T:C	F150L	0.998
11:114446007:T:A	F150L	0.998
11:114446007:T:G	F150L	0.998
11:114439668:A:T	D47V	0.996
11:114439669:C:A	D47E	0.996
11:114439669:C:G	D47E	0.996
11:114439675:G:C	E49D	0.996
11:114439675:G:T	E49D	0.996
11:114445997:A:C	D147A	0.996
11:114445997:A:T	D147V	0.996
11:114446065:A:C	S170R	0.996
11:114446067:C:A	S170R	0.996
11:114446067:C:G	S170R	0.996
11:114447830:T:A	W179R	0.996
11:114447830:T:C	W179R	0.996
11:114439668:A:C	D47A	0.995
11:114440658:G:A	M50I	0.995
11:114440658:G:C	M50I	0.995
11:114440658:G:T	M50I	0.995
11:114445988:T:A	V144D	0.995
11:114445996:G:C	D147H	0.995
11:114445998:T:A	D147E	0.995
11:114445998:T:G	D147E	0.995
11:114449881:T:C	L207P	0.995
11:114439663:G:C	W45C	0.994
11:114439663:G:T	W45C	0.994
11:114440693:A:T	E62V	0.994
11:114440694:G:C	E62D	0.994

dbSNP variants (sampled 300 via entrez): RS1000059453 (11:114446420 C>T), RS1000076132 (11:114443514 GTTC>G), RS1000407064 (11:114439894 T>G), RS1000622071 (11:114441438 A>C,G,T), RS1000970602 (11:114439294 C>T), RS1001007832 (11:114441118 A>G), RS1001116606 (11:114448086 T>C), RS1001219957 (11:114444384 G>A,C,T), RS1001232823 (11:114447140 G>A,C), RS1001268071 (11:114444890 C>T), RS1001411884 (11:114440386 A>G), RS1001684093 (11:114446883 C>T), RS1002184887 (11:114439571 G>A,C), RS1002252688 (11:114445691 C>T), RS1002365840 (11:114442101 C>T)

Disease associations

OMIM: gene MIM:607149 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
type 1 interferonopathy of childhood	Moderate	Autosomal dominant
sporadic pheochromocytoma	Limited	Autosomal dominant

Mondo (2): sporadic pheochromocytoma (MONDO:0017191), type 1 interferonopathy of childhood (MONDO:0957408)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004131_119	Inflammatory bowel disease	2.000000e-06
GCST004133_61	Ulcerative colitis	2.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3FY	Abcam HEK293T REXO2 KO	Transformed cell line	Female
CVCL_TI87	HAP1 REXO2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.