EXD3

Summary

EXD3 (exonuclease 3’-5’ domain containing 3, HGNC:26023) is a protein-coding gene on chromosome 9q34.3, encoding Exonuclease mut-7 homolog (Q8N9H8). Possesses 3’-5’ exoribonuclease activity.

Predicted to enable 3’-5’ exonuclease activity; metal ion binding activity; and nucleic acid binding activity. Predicted to be involved in nucleobase-containing compound metabolic process.

Source: NCBI Gene 54932 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 246 total
• MANE Select transcript: NM_017820

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26023
Approved symbol	EXD3
Name	exonuclease 3’-5’ domain containing 3
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	LOC54932, FLJ20433, mut-7, Nbr
Ensembl gene	ENSG00000187609
Ensembl biotype	protein_coding
OMIM	620859
Entrez	54932

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 22 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000340951, ENST00000460390, ENST00000465160, ENST00000472958, ENST00000475006, ENST00000478344, ENST00000478350, ENST00000479452, ENST00000484392, ENST00000487745, ENST00000490886, ENST00000491734, ENST00000879813, ENST00000879814, ENST00000879815, ENST00000879816, ENST00000879817, ENST00000879818, ENST00000879819, ENST00000879820, ENST00000879821, ENST00000879822, ENST00000913121, ENST00000961731, ENST00000961732, ENST00000961733, ENST00000961734, ENST00000961735, ENST00000961736, ENST00000961737, ENST00000961738

RefSeq mRNA: 2 — MANE Select: NM_017820 NM_001286823, NM_017820

CCDS: CCDS48066, CCDS75942

Canonical transcript exons

ENST00000340951 — 22 exons

Exon	Start	End
ENSE00001923999	137423114	137423162
ENSE00001948845	137306896	137307263
ENSE00003459687	137348071	137348238
ENSE00003463823	137351318	137351528
ENSE00003472108	137356268	137356368
ENSE00003485849	137373426	137373599
ENSE00003494460	137349369	137349531
ENSE00003549135	137354339	137354377
ENSE00003550383	137307608	137307646
ENSE00003567188	137309607	137309700
ENSE00003577896	137395303	137395404
ENSE00003582765	137351038	137351147
ENSE00003582879	137349110	137349282
ENSE00003583946	137352066	137352201
ENSE00003584928	137352620	137352786
ENSE00003588393	137354700	137354773
ENSE00003591793	137323725	137323856
ENSE00003618914	137324090	137324143
ENSE00003632248	137366493	137366632
ENSE00003646122	137383313	137383377
ENSE00003651996	137367936	137367989
ENSE00003672308	137372905	137373072

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 96.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1847 / max 114.5880, expressed in 1758 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103360	7.4373	1741
103361	0.7474	430

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.85	gold quality
sural nerve	UBERON:0015488	93.77	gold quality
adenohypophysis	UBERON:0002196	92.63	gold quality
tibial nerve	UBERON:0001323	91.92	gold quality
mucosa of transverse colon	UBERON:0004991	91.59	gold quality
pituitary gland	UBERON:0000007	91.20	gold quality
mucosa of stomach	UBERON:0001199	91.18	gold quality
lower esophagus mucosa	UBERON:0035834	91.08	gold quality
transverse colon	UBERON:0001157	90.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.89	gold quality
endocervix	UBERON:0000458	90.84	gold quality
left lobe of thyroid gland	UBERON:0001120	90.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.76	gold quality
lower esophagus	UBERON:0013473	90.74	gold quality
right lobe of thyroid gland	UBERON:0001119	90.66	gold quality
metanephros cortex	UBERON:0010533	90.51	gold quality
left ovary	UBERON:0002119	90.48	gold quality
left uterine tube	UBERON:0001303	90.34	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.14	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.11	gold quality
right frontal lobe	UBERON:0002810	89.94	gold quality
body of uterus	UBERON:0009853	89.94	gold quality
apex of heart	UBERON:0002098	89.57	gold quality
ectocervix	UBERON:0012249	89.55	gold quality
spleen	UBERON:0002106	89.49	gold quality
body of stomach	UBERON:0001161	89.36	gold quality
right ovary	UBERON:0002118	89.15	gold quality
thyroid gland	UBERON:0002046	89.13	gold quality
cerebellar hemisphere	UBERON:0002245	89.11	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.00	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	9.82
E-CURD-112	yes	7.35
E-ANND-3	no	3.84

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• EXD3 may be a potential oncogene in gastric cancer possibly in relation to DNA damage repair. The up-regulation of EXD3 plays an important role in the development and prognosis of gastric cancer, and may serve as an important indicator for prognostic evaluation of the patients. (PMID:30890511)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	exd3	ENSDARG00000063140
drosophila_melanogaster	Nbr	FBGN0032924
caenorhabditis_elegans		WBGENE00003504
caenorhabditis_elegans		WBGENE00014220

Paralogs (1): EXD2 (ENSG00000081177)

Protein

Protein identifiers

Exonuclease mut-7 homolog — Q8N9H8 (reviewed: Q8N9H8)

Alternative names: Exonuclease 3’-5’ domain-containing protein 3

All UniProt accessions (4): E9PI94, E9PSB6, Q8N9H8, H0YD51

UniProt curated annotations — full annotation on UniProt →

Function. Possesses 3’-5’ exoribonuclease activity. Required for 3’-end trimming of AGO1-bound miRNAs.

Similarity. Belongs to the mut-7 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8N9H8-1	1	yes
Q8N9H8-2	2
Q8N9H8-3	3
Q8N9H8-4	4
Q8N9H8-5	5

RefSeq proteins (2): NP_001273752, NP_060290* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002562	3’-5’_exonuclease_dom	Domain
IPR002782	Mut7-C_RNAse_dom	Domain
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR037432	Mut-7_DEDDy_dom	Domain
IPR052408	Exonuclease_MUT-7-like	Family

Pfam: PF01612, PF01927

UniProt features (21 total): splice variant 9, sequence conflict 6, sequence variant 2, region of interest 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N9H8-F1	79.78	0.41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): WANG_CLIM2_TARGETS_UP, GOMF_NUCLEASE_ACTIVITY, COUP_01, GOMF_EXONUCLEASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_3_5_EXONUCLEASE_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, PEDRIOLI_MIR31_TARGETS_DN, ZWANG_EGF_INTERVAL_UP, BRCA1_DN.V1_DN, chr9q34, CBX5_TARGET_GENES, CHAF1B_TARGET_GENES, FOXN3_TARGET_GENES, GLI4_TARGET_GENES

GO Biological Process (1): nucleobase-containing compound metabolic process (GO:0006139)

GO Molecular Function (7): nucleic acid binding (GO:0003676), 3’-5’ exonuclease activity (GO:0008408), metal ion binding (GO:0046872), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
primary metabolic process	1
exonuclease activity	1
cation binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
catalytic activity	1

Protein interactions and networks

STRING

810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EXD3	ZFYVE28	Q9HCC9	692
EXD3	ZNF678	Q5SXM1	669
EXD3	RBM46	Q8TBY0	646
EXD3	RECQL	P46063	593
EXD3	POLD2	P49005	581
EXD3	EXO1	Q9UQ84	576
EXD3	EXD1	Q8NHP7	570
EXD3	DNA2	P51530	549
EXD3	POLD1	P28340	541
EXD3	SIRT6	Q8N6T7	492
EXD3	XRCC5	P13010	490
EXD3	MMUT	P22033	478
EXD3	DBF4B	Q8NFT6	471
EXD3	XRCC6	P12956	469
EXD3	TOP3A	Q13472	465

IntAct

9 interactions, top by confidence:

A	B	Type	Score
EXD3	DAZAP2	psi-mi:“MI:0915”(physical association)	0.620
DAZAP2	EXD3	psi-mi:“MI:0915”(physical association)	0.620
GASK1B	EXD3	psi-mi:“MI:0915”(physical association)	0.400
EXD3	EXD3	psi-mi:“MI:0915”(physical association)	0.370
PLSCR1	EXD3	psi-mi:“MI:0915”(physical association)	0.370
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
EXD3	TMBIM6	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): EXD3 (Two-hybrid), EXD3 (Two-hybrid), EXD3 (Two-hybrid), EXD3 (Affinity Capture-RNA), EXD3 (Proximity Label-MS), TMBIM6 (Affinity Capture-MS), EXD3 (Affinity Capture-MS), PSME4 (Affinity Capture-MS), EXD3 (Cross-Linking-MS (XL-MS)), EXD3 (Affinity Capture-MS), DAZAP2 (Two-hybrid)

ESM2 similar proteins: A0A5F4BST2, A0PJX4, A0RZB4, A1L515, A2A9Q0, A2BDG0, A6QQ85, A6XN32, A9JSM3, B0FP48, D3YZZ2, D4A2Q0, E5RIL1, F1SAM7, P01183, Q1RMK9, Q3UPR0, Q3ZCQ3, Q5BIV7, Q5BIV9, Q5BK01, Q5GH56, Q5GH64, Q5GH72, Q5SNT2, Q5T7M4, Q6IEE6, Q6PRD1, Q6UWJ8, Q70RD5, Q864V4, Q86UD0, Q8BWU1, Q8BX43, Q8CCB5, Q8IVY1, Q8K064, Q8K2Y3, Q8K5A9, Q8N9H8

Diamond homologs: A0KXU5, A1SVE6, A5G127, A6V8R6, A7HYE5, A8GFH0, A9H9B7, C6C608, C9XUE4, D4Z694, P09155, P44442, Q0BVP4, Q5GZ75, Q5NPM2, Q6AJF4, Q8N9H8, A1CJ18, A2QY39, A4R715, A6RY31, A8WK63, B3LWP6, B3NZ68, B4G5C9, B4I298, B4JF25, B4K934, B4M401, B4N9D3, B4PLB3, B4QUF6, D4ACP5, O09053, O18017, O34748, O88700, O93530, O94761, O94762

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	190
Likely benign	15
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

6858 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137323720:CCCA:C	donor_loss	1.0000
9:137323721:CCAC:C	donor_loss	1.0000
9:137323722:CA:C	donor_loss	1.0000
9:137323723:ACCTG:A	donor_loss	1.0000
9:137351316:AC:A	donor_gain	1.0000
9:137351317:CC:C	donor_gain	1.0000
9:137351317:CCCAG:C	donor_gain	1.0000
9:137351321:G:C	donor_gain	1.0000
9:137351524:TGGCA:T	acceptor_gain	1.0000
9:137351525:GGCA:G	acceptor_gain	1.0000
9:137351526:GCA:G	acceptor_gain	1.0000
9:137351527:CA:C	acceptor_gain	1.0000
9:137351527:CAC:C	acceptor_gain	1.0000
9:137351528:ACT:A	acceptor_loss	1.0000
9:137351529:C:CC	acceptor_gain	1.0000
9:137351529:C:CG	acceptor_loss	1.0000
9:137351530:T:C	acceptor_loss	1.0000
9:137352615:CTCA:C	donor_loss	1.0000
9:137352616:TCAC:T	donor_loss	1.0000
9:137352617:CA:C	donor_loss	1.0000
9:137352618:A:C	donor_loss	1.0000
9:137352618:ACCT:A	donor_gain	1.0000
9:137352618:ACCTC:A	donor_gain	1.0000
9:137352619:C:CT	donor_loss	1.0000
9:137352619:CCTC:C	donor_gain	1.0000
9:137352619:CCTCC:C	donor_gain	1.0000
9:137352621:T:TA	donor_gain	1.0000
9:137352622:C:A	donor_gain	1.0000
9:137352623:C:A	donor_gain	1.0000
9:137352725:C:CC	acceptor_gain	1.0000

AlphaMissense

5642 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137324118:A:T	I675N	0.992
9:137324118:A:G	I675T	0.988
9:137324115:A:T	L676Q	0.987
9:137307064:G:C	F839L	0.985
9:137307064:G:T	F839L	0.985
9:137307066:A:G	F839L	0.985
9:137324112:G:T	T677K	0.983
9:137324118:A:C	I675S	0.982
9:137348135:A:T	L645H	0.982
9:137323819:A:T	V697D	0.981
9:137348180:A:G	F630S	0.979
9:137323729:C:G	C727S	0.978
9:137323730:A:T	C727S	0.978
9:137323767:G:C	F714L	0.978
9:137323767:G:T	F714L	0.978
9:137323769:A:G	F714L	0.978
9:137348167:A:C	C634W	0.978
9:137307074:C:A	G836V	0.977
9:137348165:T:A	D635V	0.977
9:137309692:G:C	N731K	0.976
9:137309692:G:T	N731K	0.976
9:137309693:T:A	N731I	0.976
9:137323737:G:C	F724L	0.976
9:137323737:G:T	F724L	0.976
9:137323739:A:G	F724L	0.976
9:137324123:C:A	R673S	0.976
9:137324123:C:G	R673S	0.976
9:137348168:C:T	C634Y	0.976
9:137349409:C:A	W539C	0.976
9:137349409:C:G	W539C	0.976

dbSNP variants (sampled 300 via entrez): RS1000050037 (9:137368812 G>C), RS1000055878 (9:137399732 A>C,G), RS1000059934 (9:137334238 G>T), RS1000080042 (9:137400904 G>A), RS1000084020 (9:137368767 C>G,T), RS1000106661 (9:137337632 C>A), RS1000125264 (9:137330342 C>A,G,T), RS1000139126 (9:137306634 G>A), RS1000171685 (9:137379812 C>T), RS1000187296 (9:137311360 A>C), RS1000191789 (9:137316160 C>G,T), RS1000207124 (9:137419652 G>C), RS1000211339 (9:137372841 C>G,T), RS1000218924 (9:137313796 A>C), RS1000220077 (9:137339434 G>A)

Disease associations

OMIM: gene MIM:620859 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST003771_17	Loneliness	8.000000e-06
GCST003837_7	Chronotype	2.000000e-12
GCST003838_7	Morning vs. evening chronotype	7.000000e-09
GCST007565_149	Morning person	1.000000e-33
GCST007576_6	Chronotype	1.000000e-33
GCST008512_26	Multisite chronic pain	5.000000e-14
GCST012332_24	Multisite chronic pain	6.000000e-12
GCST012332_25	Multisite chronic pain	7.000000e-09
GCST012332_26	Multisite chronic pain	3.000000e-14
GCST012333_2	Multisite chronic pain	3.000000e-09
GCST90000025_389	Appendicular lean mass	2.000000e-09
GCST90000047_203	Age at first sexual intercourse	2.000000e-08
GCST90000050_64	Age at first birth	4.000000e-08
GCST90002401_201	Platelet distribution width	6.000000e-14

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007865	loneliness measurement
EFO:0008328	chronotype measurement
EFO:0010100	multisite chronic pain
EFO:0004980	appendicular lean mass
EFO:0009749	age at first sexual intercourse measurement
EFO:0009101	age at first birth measurement
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	6
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
bisphenol A	increases expression, affects expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
afuresertib	increases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
trichostatin A	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Arsenic	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Methapyrilene	decreases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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