TATDN3

Summary

TATDN3 (TatD DNase domain containing 3, HGNC:27010) is a protein-coding gene on chromosome 1q32.3, encoding Deoxyribonuclease TATDN3 (Q17R31). Exhibits 3’-exonuclease and apurinic/apyrimidinic (AP) endonuclease activities (in vitro).

Predicted to enable metal ion binding activity and nuclease activity. Located in mitochondrion.

Source: NCBI Gene 128387 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_001042552

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27010
Approved symbol	TATDN3
Name	TatD DNase domain containing 3
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000203705
Ensembl biotype	protein_coding
Entrez	128387

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 24 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000366973, ENST00000366974, ENST00000488246, ENST00000497768, ENST00000525569, ENST00000525574, ENST00000526641, ENST00000526997, ENST00000527693, ENST00000530392, ENST00000530399, ENST00000530441, ENST00000531963, ENST00000532324, ENST00000532433, ENST00000533650, ENST00000606486, ENST00000883558, ENST00000883559, ENST00000883560, ENST00000883561, ENST00000883562, ENST00000933544, ENST00000933545, ENST00000933546, ENST00000933547, ENST00000933548, ENST00000950484, ENST00000950485, ENST00000950486

RefSeq mRNA: 7 — MANE Select: NM_001042552 NM_001042552, NM_001042553, NM_001146169, NM_001146170, NM_001146171, NM_001363589, NM_001363590

CCDS: CCDS31019, CCDS41465, CCDS53475, CCDS53476, CCDS53477, CCDS86050

Canonical transcript exons

ENST00000366974 — 10 exons

Exon	Start	End
ENSE00003512317	212795095	212795127
ENSE00003519319	212807736	212807848
ENSE00003594586	212797112	212797196
ENSE00003599942	212802701	212802763
ENSE00003604541	212796517	212796590
ENSE00003606287	212815013	212816830
ENSE00003642377	212812248	212812328
ENSE00003664783	212804320	212804429
ENSE00003789373	212804596	212804651
ENSE00003847569	212791894	212791987

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 91.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2891 / max 157.8898, expressed in 1794 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8488	12.1916	1794
8489	0.0975	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	91.59	gold quality
vastus lateralis	UBERON:0001379	91.19	gold quality
quadriceps femoris	UBERON:0001377	90.09	gold quality
calcaneal tendon	UBERON:0003701	89.71	gold quality
islet of Langerhans	UBERON:0000006	89.65	gold quality
corpus callosum	UBERON:0002336	89.53	gold quality
buccal mucosa cell	CL:0002336	89.28	gold quality
skeletal muscle tissue	UBERON:0001134	89.15	gold quality
monocyte	CL:0000576	89.00	gold quality
leukocyte	CL:0000738	88.61	gold quality
biceps brachii	UBERON:0001507	88.39	gold quality
muscle tissue	UBERON:0002385	88.18	gold quality
deltoid	UBERON:0001476	88.14	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.52	gold quality
muscle of leg	UBERON:0001383	87.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.10	gold quality
myocardium	UBERON:0002349	87.08	silver quality
Brodmann (1909) area 23	UBERON:0013554	87.02	gold quality
gastrocnemius	UBERON:0001388	87.01	gold quality
lateral globus pallidus	UBERON:0002476	86.64	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.58	gold quality
substantia nigra pars compacta	UBERON:0001965	86.50	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.49	silver quality
prefrontal cortex	UBERON:0000451	86.47	gold quality
medial globus pallidus	UBERON:0002477	86.35	gold quality
primary visual cortex	UBERON:0002436	86.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.20	gold quality
globus pallidus	UBERON:0001875	86.19	gold quality
renal medulla	UBERON:0000362	85.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.12
E-MTAB-6379	no	364.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting TATDN3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6875-3P	99.82	70.26	2983

Literature-anchored findings (GeneRIF, showing 1)

• Human and bacterial TatD enzymes exhibit apurinic/apyrimidinic (AP) endonuclease activity. (PMID:36881763)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	TATDN3	ENSDARG00000044072
mus_musculus	Tatdn3	ENSMUSG00000026632
rattus_norvegicus	AABR07022144.1	ENSRNOG00000046460
caenorhabditis_elegans		WBGENE00015189

Paralogs (2): TATDN1 (ENSG00000147687), TATDN2 (ENSG00000157014)

Protein

Protein identifiers

Deoxyribonuclease TATDN3 — Q17R31 (reviewed: Q17R31)

Alternative names: DNA-(apurinic or apyrimidinic site) endonuclease TATDN3, TatD DNase domain containing 3

All UniProt accessions (9): Q17R31, E9PP81, E9PPF0, E9PQP8, E9PRA1, H0YCC7, H0YCN0, H0YD82, U3KQ29

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits 3’-exonuclease and apurinic/apyrimidinic (AP) endonuclease activities (in vitro). Show preferential AP endonuclease activity on double-stranded DNA substrates and 3’- exonuclease activity on single-stranded DNA.

Subcellular location. Nucleus.

Activity regulation. The 3’-exonuclease activity is sensitive to the metal ion present in the active site, whereas the AP endodeoxyribonuclease activity is observed in a variety of divalent metal cofactors. 3’-exoxonuclease activity is suppressed in the presence of Ca(2+), Zn(2+) and Ni(2+).

Cofactor. Binds 2 Zn(2+) per subunit. Exhibits AP endonuclease and 3’-exonuclease activities in the presence of Mg(2+) and Mn(2+). In contrast, in the presence of Ca(2+), shows AP endonuclease activity exclusively.

Similarity. Belongs to the metallo-dependent hydrolases superfamily. TatD-type hydrolase family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q17R31-1	1	yes
Q17R31-2	2
Q17R31-3	3
Q17R31-4	4
Q17R31-5	5

RefSeq proteins (7): NP_001036017, NP_001036018, NP_001139641, NP_001139642, NP_001139643, NP_001350518, NP_001350519 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001130	TatD-like	Family
IPR032466	Metal_Hydrolase	Homologous_superfamily

Pfam: PF01026

UniProt features (45 total): helix 16, strand 8, binding site 7, splice variant 4, mutagenesis site 3, sequence conflict 3, turn 3, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2Y1H	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q17R31-F1	96.17	0.94

Functional residue map

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

Ligand- & substrate-binding residues (7): 12; 14; 107; 107; 147; 170; 218

Mutagenesis-validated functional residues (3):

Position	Phenotype
107	reduces ap endodeoxyribonuclease and 3’-exonuclease activities.
107	increases both ap endodeoxyribonuclease and 3’-exonuclease activities.
218	reduces both ap endodeoxyribonuclease and 3’-exonuclease activities by 30-fold.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOMF_EXONUCLEASE_ACTIVITY, GOMF_DNA_ENDONUCLEASE_ACTIVITY, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOBP_DNA_METABOLIC_PROCESS, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_3_5_EXONUCLEASE_ACTIVITY, GOMF_DNA_EXONUCLEASE_ACTIVITY, CHEN_LIVER_METABOLISM_QTL_CIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, FORTSCHEGGER_PHF8_TARGETS_DN, GOMF_DNA_APURINIC_OR_APYRIMIDINIC_SITE_ENDONUCLEASE_ACTIVITY, GOMF_3_5_DNA_EXONUCLEASE_ACTIVITY

GO Biological Process (1): DNA metabolic process (GO:0006259)

GO Molecular Function (7): DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0003906), single-stranded DNA 3’-5’ DNA exonuclease activity (GO:0008310), metal ion binding (GO:0046872), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788)

GO Cellular Component (2): nucleus (GO:0005634), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
nucleic acid metabolic process	1
DNA endonuclease activity	1
3’-5’-DNA exonuclease activity	1
single-stranded DNA exodeoxyribonuclease activity	1
cation binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
catalytic activity	1
hydrolase activity	1
cytoplasm	1

Protein interactions and networks

STRING

624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TATDN3	BEND7	Q8N7W2	625
TATDN3	OTOL1	A6NHN0	605
TATDN3	ANGEL2	Q5VTE6	593
TATDN3	LYPD6B	Q8NI32	570
TATDN3	RPS6KC1	Q96S38	551
TATDN3	ST8SIA5	O15466	549
TATDN3	KATNAL2	Q8IYT4	530
TATDN3	GPCPD1	Q9NPB8	530
TATDN3	EIF1AD	Q8N9N8	522
TATDN3	SHLD1	Q8IYI0	518
TATDN3	LOXHD1	Q8IVV2	513
TATDN3	SKAP2	O75563	487
TATDN3	CNOT6L	Q96LI5	486
TATDN3	SEC61A2	Q9H9S3	478
TATDN3	PHYH	O14832	469

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MSH6	PCNA	psi-mi:“MI:0914”(association)	0.530
ARFGEF1	AKAP10	psi-mi:“MI:0914”(association)	0.350
TATDN3	HSPA2	psi-mi:“MI:0914”(association)	0.350
MRPS14	MRPS25	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): TATDN3 (Affinity Capture-MS), TATDN3 (Affinity Capture-MS), TATDN3 (Affinity Capture-MS), TATDN3 (Affinity Capture-MS), TATDN3 (Affinity Capture-RNA), TATDN3 (Affinity Capture-MS), TATDN3 (Affinity Capture-MS), TATDN3 (Affinity Capture-MS), HSPA2 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), TATDN3 (Protein-peptide), TATDN3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4M4, A4JPX7, A6TAC4, A7ZI99, A7ZWZ9, B1J0S7, B1LIN7, B2JQW0, B5XQJ4, B5Z2Q7, B6HZX8, B7L508, B7M300, B7MPB9, B7N8Q9, B7NK03, C1DF10, C1DRJ0, O95620, P00813, P03958, P51020, P56658, Q05AV0, Q0VC13, Q13QH6, Q13VU3, Q17R31, Q32M08, Q3U1C6, Q3Z554, Q46NW8, Q47B13, Q4V831, Q4V9P6, Q503T5, Q56Y42, Q5ZKP6, Q63ZU0, Q640V9

Diamond homologs: A1A4M4, P0AFQ7, P0AFQ8, P0AFQ9, P37545, P44718, P57436, Q05AV0, Q17R31, Q3U1C6, Q503T5, Q58977, Q6GPM3, Q8K9J1, A4WFX9, A7MQN1, A8G8C4, B1JP69, B2VG45, B5XYH5, B7LTZ5, C6C4V4, C6DI71, C9XTA5, D0Z9R0, D4GGR2, D4ICL5, D8MKW4, E1SKR8, E3G381, E6WHK1, E8XYF5, O08343, P73335, P78005, Q0SZ31, Q6DAQ1, Q9L6M2, Q9PRC8, A8ACY8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1589 predictions. Top by Δscore:

Variant	Effect	Δscore
1:212791986:GC:G	donor_gain	1.0000
1:212791988:G:GG	donor_gain	1.0000
1:212791997:GGCGA:G	donor_gain	1.0000
1:212792015:G:GT	donor_gain	1.0000
1:212792022:G:GT	donor_gain	1.0000
1:212792023:G:T	donor_gain	1.0000
1:212795089:TTTTA:T	acceptor_loss	1.0000
1:212795090:TTTA:T	acceptor_loss	1.0000
1:212795091:TTA:T	acceptor_loss	1.0000
1:212795092:TAGGA:T	acceptor_loss	1.0000
1:212795093:A:AG	acceptor_gain	1.0000
1:212795093:AG:A	acceptor_gain	1.0000
1:212795094:G:GT	acceptor_gain	1.0000
1:212795094:GG:G	acceptor_gain	1.0000
1:212795124:GAAG:G	donor_gain	1.0000
1:212795125:AAGG:A	donor_loss	1.0000
1:212795126:AG:A	donor_gain	1.0000
1:212795126:AGGTA:A	donor_loss	1.0000
1:212795127:GG:G	donor_gain	1.0000
1:212795128:G:GG	donor_gain	1.0000
1:212795129:T:A	donor_loss	1.0000
1:212804428:GT:G	donor_gain	1.0000
1:212804430:G:GG	donor_gain	1.0000
1:212807802:C:G	donor_gain	1.0000
1:212812245:A:AG	acceptor_gain	1.0000
1:212812246:A:G	acceptor_gain	1.0000
1:212791983:ACCGC:A	donor_gain	0.9900
1:212791984:CCGC:C	donor_gain	0.9900
1:212791985:CGCG:C	donor_loss	0.9900
1:212791986:GCGTA:G	donor_loss	0.9900

AlphaMissense

1758 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:212807762:T:C	F172L	0.999
1:212807764:T:A	F172L	0.999
1:212807764:T:G	F172L	0.999
1:212812300:A:T	D218V	0.999
1:212807756:C:G	H170D	0.998
1:212812299:G:C	D218H	0.998
1:212812301:T:A	D218E	0.998
1:212812301:T:G	D218E	0.998
1:212802762:A:T	E107V	0.997
1:212804327:T:C	L110P	0.997
1:212804603:C:G	H147D	0.997
1:212812294:A:T	E216V	0.997
1:212812297:C:T	T217I	0.997
1:212812300:A:C	D218A	0.997
1:212812300:A:G	D218G	0.997
1:212791955:C:G	H12D	0.996
1:212791961:C:G	H14D	0.996
1:212791963:C:A	H14Q	0.996
1:212791963:C:G	H14Q	0.996
1:212804324:G:A	G109E	0.996
1:212804387:T:C	L130P	0.996
1:212804605:C:A	H147Q	0.996
1:212804605:C:G	H147Q	0.996
1:212804606:T:C	S148P	0.996
1:212804610:G:C	R149P	0.996
1:212804616:C:A	A151D	0.996
1:212807758:T:A	H170Q	0.996
1:212807758:T:G	H170Q	0.996
1:212812295:A:C	E216D	0.996
1:212812295:A:T	E216D	0.996

dbSNP variants (sampled 300 via entrez): RS1000018291 (1:212795385 C>G), RS1000023862 (1:212790040 G>C), RS1000527446 (1:212799928 C>A), RS1000619424 (1:212813830 CCT>C), RS1000671881 (1:212813487 CTA>C), RS1000957522 (1:212802462 G>A,T), RS1000966156 (1:212807269 T>A), RS1001081188 (1:212800249 C>T), RS1001180401 (1:212810727 T>C), RS1001199116 (1:212803451 T>G), RS1001518426 (1:212790910 G>A,C), RS1001544926 (1:212809305 G>A), RS1001631483 (1:212810348 T>A), RS1001678414 (1:212799206 T>C), RS1001967323 (1:212813943 A>G)

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

2 associations (top):

Study	Trait	p-value
GCST90013445_18	Type 1 diabetes	2.000000e-08
GCST90013445_32	Type 1 diabetes	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases oxidation, increases expression, affects cotreatment, increases abundance	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
afimoxifene	decreases expression, decreases reaction	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
resorcinol	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
ICG 001	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Succimer	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Estrogens	decreases expression, decreases reaction	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Testosterone	increases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases expression	1

Clinical trials (associated diseases)

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