REXO5

Summary

REXO5 (RNA exonuclease 5, HGNC:24661) is a protein-coding gene on chromosome 16p12.3, encoding RNA exonuclease 5 (Q96IC2).

Predicted to enable exonuclease activity. Predicted to be involved in rRNA 3’-end processing. Located in nucleolus.

Source: NCBI Gene 81691 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_030941

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24661
Approved symbol	REXO5
Name	RNA exonuclease 5
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	NEF-sp
Ensembl gene	ENSG00000005189
Ensembl biotype	protein_coding
Entrez	81691

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 24 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000261377, ENST00000348433, ENST00000561474, ENST00000563045, ENST00000563068, ENST00000563617, ENST00000564200, ENST00000564274, ENST00000565340, ENST00000566276, ENST00000566518, ENST00000566993, ENST00000567297, ENST00000568046, ENST00000568334, ENST00000568476, ENST00000568501, ENST00000568647, ENST00000568894, ENST00000909368, ENST00000909369, ENST00000909370, ENST00000909371, ENST00000909372, ENST00000909373, ENST00000919604, ENST00000919605, ENST00000919606, ENST00000956103, ENST00000956104, ENST00000956105

RefSeq mRNA: 3 — MANE Select: NM_030941 NM_001144924, NM_001199053, NM_030941

CCDS: CCDS10591, CCDS45437

Canonical transcript exons

ENST00000261377 — 20 exons

Exon	Start	End
ENSE00001419737	20849399	20849665
ENSE00002613806	20806527	20806705
ENSE00003460998	20825833	20825948
ENSE00003478635	20814927	20815053
ENSE00003498767	20839755	20839859
ENSE00003518373	20821762	20821902
ENSE00003520676	20816116	20816212
ENSE00003527781	20824439	20824527
ENSE00003537565	20828435	20828537
ENSE00003549632	20833003	20833123
ENSE00003561587	20846221	20846339
ENSE00003563958	20843934	20844026
ENSE00003604890	20827058	20827196
ENSE00003615038	20806952	20807091
ENSE00003629181	20832156	20832259
ENSE00003636250	20827353	20827447
ENSE00003636400	20844629	20844845
ENSE00003642095	20845054	20845241
ENSE00003647596	20813190	20813302
ENSE00003670863	20840331	20840468

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 98.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3423 / max 610.3180, expressed in 1452 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153071	3.2253	876
153073	2.3203	1009
153070	1.0100	350
153072	0.6386	305
153074	0.0867	8
153075	0.0311	3
153076	0.0172	3
153069	0.0130	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.87	gold quality
right testis	UBERON:0004534	98.81	gold quality
adult organism	UBERON:0007023	98.75	gold quality
testis	UBERON:0000473	96.55	gold quality
male germ cell	CL:0000015	94.65	gold quality
sperm	CL:0000019	94.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.92	gold quality
ventricular zone	UBERON:0003053	82.38	gold quality
ganglionic eminence	UBERON:0004023	81.72	gold quality
body of stomach	UBERON:0001161	78.74	gold quality
right uterine tube	UBERON:0001302	78.56	gold quality
stomach	UBERON:0000945	76.17	gold quality
adrenal tissue	UBERON:0018303	75.71	gold quality
bone marrow	UBERON:0002371	75.06	gold quality
embryo	UBERON:0000922	74.88	gold quality
bone marrow cell	CL:0002092	74.85	gold quality
right adrenal gland	UBERON:0001233	74.23	gold quality
rectum	UBERON:0001052	73.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	73.59	gold quality
right adrenal gland cortex	UBERON:0035827	73.56	gold quality
cortical plate	UBERON:0005343	73.42	gold quality
left adrenal gland	UBERON:0001234	72.61	gold quality
cerebellar hemisphere	UBERON:0002245	72.42	gold quality
cerebellar cortex	UBERON:0002129	72.36	gold quality
prostate gland	UBERON:0002367	72.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.07	gold quality
smooth muscle tissue	UBERON:0001135	71.94	gold quality
left adrenal gland cortex	UBERON:0035825	71.54	gold quality
adrenal gland	UBERON:0002369	71.36	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.87
E-ANND-3	yes	12.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting REXO5, 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-5582-3P	99.86	72.48	4221
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-4423-3P	97.98	69.66	912
HSA-MIR-3936	97.64	64.47	732
HSA-MIR-555	95.92	65.25	564

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rexo5	ENSMUSG00000030924
rattus_norvegicus	Rexo5	ENSRNOG00000014513
drosophila_melanogaster	CG12877	FBGN0039544
drosophila_melanogaster	prage	FBGN0283741
caenorhabditis_elegans		WBGENE00004095

Paralogs (5): REXO1 (ENSG00000079313), ISG20L2 (ENSG00000143319), REXO4 (ENSG00000148300), ISG20 (ENSG00000172183), AEN (ENSG00000181026)

Protein

Protein identifiers

RNA exonuclease 5 — Q96IC2 (reviewed: Q96IC2)

Alternative names: Exonuclease NEF-sp

All UniProt accessions (12): Q96IC2, H3BM72, H3BPB2, H3BQ98, H3BQP3, H3BR13, H3BRC7, H3BRG1, H3BSC5, H3BSE4, H3BUT7, H3BV93

Isoforms (2)

UniProt ID	Names	Canonical?
Q96IC2-1	1	yes
Q96IC2-2	2

RefSeq proteins (3): NP_001138396, NP_001185982, NP_112203* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR013520	Ribonucl_H	Domain
IPR034922	REX1-like_exo	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR047021	REXO1/3/4-like	Family

Pfam: PF00076, PF00929

UniProt features (10 total): domain 3, sequence conflict 3, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96IC2-F1	78.33	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_RIBOSOME_BIOGENESIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOMF_NUCLEASE_ACTIVITY, SASSON_RESPONSE_TO_FORSKOLIN_DN, GNF2_CCNA1, MORF_RAB3A, MORF_BMPR2, GOBP_RRNA_3_END_PROCESSING, GOMF_EXONUCLEASE_ACTIVITY, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, CETS1P54_01, KONDO_PROSTATE_CANCER_HCP_WITH_H3K27ME3

GO Biological Process (1): rRNA 3’-end processing (GO:0031125)

GO Molecular Function (5): RNA binding (GO:0003723), exonuclease activity (GO:0004527), nucleic acid binding (GO:0003676), nuclease activity (GO:0004518), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleus (GO:0005634), nucleolus (GO:0005730), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
rRNA processing	1
RNA 3’-end processing	1
nucleic acid binding	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
binding	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

1050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
REXO5	REXO2	Q9Y3B8	502
REXO5	TTC31	Q49AM3	455
REXO5	Q8WV35	Q8WV35	412
REXO5	REP15	Q6BDI9	402
REXO5	SPINK9	Q5DT21	393
REXO5	DEDD	O75618	390
REXO5	DIS3	Q9Y2L1	368
REXO5	EXOSC10	Q01780	365
REXO5	ZNHIT6	Q9NWK9	349
REXO5	BDKRB2	P30411	348
REXO5	SAP30L	Q9HAJ7	348
REXO5	RPF2	Q9H7B2	341
REXO5	RHOXF2	Q9BQY4	336
REXO5	POLR1A	O95602	332
REXO5	ZNF322	Q6U7Q0	325
REXO5	SYNRG	Q9UMZ2	325

IntAct

34 interactions, top by confidence:

A	B	Type	Score
MAX	E2F6	psi-mi:“MI:0914”(association)	0.710
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
WDR55	PES1	psi-mi:“MI:0914”(association)	0.530
UBA5	GAPDHS	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
DCAF8	TCP1	psi-mi:“MI:0914”(association)	0.530
REXO5	IGBP1	psi-mi:“MI:0915”(physical association)	0.370
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
PTGES3	KIFBP	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
RAMP2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
LURAP1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
PER2	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
TENT5A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
DNAJA2	DENND11	psi-mi:“MI:0914”(association)	0.350
INSYN1	CCDC85C	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
SKAP1	MYO9A	psi-mi:“MI:0914”(association)	0.350
DQX1	MYO9A	psi-mi:“MI:0914”(association)	0.350
MAX	AGRN	psi-mi:“MI:0914”(association)	0.350
NOL4	ZNF195	psi-mi:“MI:0914”(association)	0.350
PKD1L2	MAP3K7	psi-mi:“MI:0914”(association)	0.350
LMNB2	SPOP	psi-mi:“MI:0914”(association)	0.350
OC90	ZNF324	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Proximity Label-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS), LOC81691 (Affinity Capture-MS)

ESM2 similar proteins: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A6NDS4, A6NER0, A6NMD0, A6QPT6, B9A6J9, M3WHG5, O15482, O15553, O19110, O76081, P0C7X1, P0C7X3, P0C7X4, P35125, P48778, P48967, P48968, P79209, Q13670, Q15697, Q2TBC4, Q3T191, Q3UZD7, Q4R2Z8, Q5DRQ5, Q5SSQ6, Q69ZB3, Q6DHY5, Q6IPX1, Q6ZMN8, Q8BLR5, Q8IYF1, Q8IZP1, Q8JZW5, Q8N7G0, Q8N831

Diamond homologs: A1A5R7, A1Z7K9, A3KPE8, A3LRV8, A4RF51, A5DAD0, A5E1W0, B2GUW6, G0SAK8, O94375, O94443, P0C581, P0CQ08, P0CQ09, P0CQ44, P0CQ45, P48778, P53010, P53015, P53331, Q08237, Q09798, Q0CJU7, Q10124, Q2GSV2, Q2T9U5, Q2YDK1, Q3U1G5, Q4PER6, Q4R9F7, Q4WYA1, Q504Q3, Q54U94, Q5AL29, Q5APK0, Q5B367, Q5F450, Q5REE2, Q6AXU3, Q6C462

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	10
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3145 predictions. Top by Δscore:

Variant	Effect	Δscore
16:20806397:C:CA	donor_gain	1.0000
16:20821756:TTTCA:T	acceptor_loss	1.0000
16:20821757:TTCA:T	acceptor_loss	1.0000
16:20821758:TCAG:T	acceptor_loss	1.0000
16:20821760:A:AG	acceptor_gain	1.0000
16:20821760:AG:A	acceptor_gain	1.0000
16:20821760:AGG:A	acceptor_gain	1.0000
16:20821761:G:GT	acceptor_gain	1.0000
16:20821761:GG:G	acceptor_gain	1.0000
16:20821761:GGG:G	acceptor_gain	1.0000
16:20821761:GGGC:G	acceptor_gain	1.0000
16:20821761:GGGCC:G	acceptor_gain	1.0000
16:20821869:G:GT	donor_gain	1.0000
16:20821872:GAAA:G	donor_gain	1.0000
16:20821873:A:T	donor_gain	1.0000
16:20821880:A:T	donor_gain	1.0000
16:20825831:A:AG	acceptor_gain	1.0000
16:20825832:G:GA	acceptor_gain	1.0000
16:20827050:A:AG	acceptor_gain	1.0000
16:20827050:AAT:A	acceptor_gain	1.0000
16:20827051:A:AG	acceptor_gain	1.0000
16:20827051:AT:A	acceptor_gain	1.0000
16:20827052:T:A	acceptor_gain	1.0000
16:20827052:T:G	acceptor_gain	1.0000
16:20827055:A:AG	acceptor_gain	1.0000
16:20827056:A:AG	acceptor_gain	1.0000
16:20827057:G:GA	acceptor_gain	1.0000
16:20827192:TGAAA:T	donor_gain	1.0000
16:20827193:GAAA:G	donor_gain	1.0000
16:20827193:GAAAG:G	donor_gain	1.0000

AlphaMissense

5072 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:20814928:T:A	W85R	0.992
16:20814928:T:C	W85R	0.992
16:20845056:T:C	F647L	0.978
16:20845058:C:A	F647L	0.978
16:20845058:C:G	F647L	0.978
16:20816119:T:C	F128L	0.975
16:20816120:T:C	F128S	0.975
16:20816121:C:A	F128L	0.975
16:20816121:C:G	F128L	0.975
16:20844716:T:G	Y603D	0.974
16:20814971:T:A	V99D	0.972
16:20849428:T:C	L758P	0.972
16:20839767:G:C	A466P	0.971
16:20839804:T:A	V478D	0.970
16:20813268:G:C	A73P	0.969
16:20814930:G:C	W85C	0.969
16:20814930:G:T	W85C	0.969
16:20846321:T:C	L742P	0.969
16:20813248:T:C	L66P	0.965
16:20813260:T:C	L70P	0.964
16:20815045:T:C	F124L	0.963
16:20815047:C:A	F124L	0.963
16:20815047:C:G	F124L	0.963
16:20815003:T:C	F110L	0.962
16:20815005:T:A	F110L	0.962
16:20815005:T:G	F110L	0.962
16:20844720:T:C	L604P	0.962
16:20846311:T:C	C739R	0.961
16:20814931:T:C	C86R	0.960
16:20843953:A:C	Y549S	0.960

dbSNP variants (sampled 300 via entrez): RS1000040819 (16:20829983 C>T), RS1000122437 (16:20814607 G>C), RS1000222682 (16:20842613 G>A), RS1000234852 (16:20822468 A>T), RS1000272691 (16:20843267 C>T), RS1000334380 (16:20814916 T>C,G), RS1000636659 (16:20841971 G>A), RS1000734951 (16:20833798 G>A), RS1000737466 (16:20835495 C>G,T), RS1000766602 (16:20834333 C>A,G,T), RS1000776653 (16:20806614 A>G,T), RS1000784025 (16:20849538 A>C), RS1000849229 (16:20807856 G>C), RS1000853138 (16:20807178 C>T), RS1000969582 (16:20820815 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
sodium arsenite	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Dihydrotestosterone	increases expression	1
Urethane	decreases expression	1
Cadmium Chloride	increases expression	1
Volatile Organic Compounds	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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