TATDN1

Summary

TATDN1 (TatD DNase domain containing 1, HGNC:24220) is a protein-coding gene on chromosome 8q24.13, encoding Deoxyribonuclease TATDN1 (Q6P1N9). Exhibits 3’-5’ exonuclease and apurinic/apyrimidinic (AP) endonuclease activities (in vitro).

Predicted to enable 3’-5’-DNA exonuclease activity. Predicted to be involved in DNA metabolic process. Located in nucleoplasm.

Source: NCBI Gene 83940 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_032026

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24220
Approved symbol	TATDN1
Name	TatD DNase domain containing 1
Location	8q24.13
Locus type	gene with protein product
Status	Approved
Aliases	CDA11
Ensembl gene	ENSG00000147687
Ensembl biotype	protein_coding
OMIM	619364
Entrez	83940

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 23 protein_coding, 6 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000276692, ENST00000517678, ENST00000518133, ENST00000518485, ENST00000519232, ENST00000519548, ENST00000519776, ENST00000520321, ENST00000520938, ENST00000521546, ENST00000521973, ENST00000522280, ENST00000522310, ENST00000522810, ENST00000522927, ENST00000523152, ENST00000523214, ENST00000523631, ENST00000523888, ENST00000605953, ENST00000630259, ENST00000866113, ENST00000866114, ENST00000933707, ENST00000933708, ENST00000933709, ENST00000933710, ENST00000933711, ENST00000933712, ENST00000933713, ENST00000933714, ENST00000933715, ENST00000933716, ENST00000933717, ENST00000933718

RefSeq mRNA: 5 — MANE Select: NM_032026 NM_001146160, NM_001317889, NM_001317890, NM_001317891, NM_032026

CCDS: CCDS55273, CCDS6351, CCDS83323

Canonical transcript exons

ENST00000276692 — 12 exons

Exon	Start	End
ENSE00002108222	124539025	124539085
ENSE00003459987	124522151	124522200
ENSE00003478024	124518818	124518881
ENSE00003490703	124504271	124504347
ENSE00003575851	124515887	124516030
ENSE00003606883	124488498	124488696
ENSE00003613462	124493833	124493959
ENSE00003613985	124508603	124508688
ENSE00003637673	124495472	124495542
ENSE00003659206	124522937	124523002
ENSE00003676311	124515746	124515788
ENSE00003785565	124508474	124508514

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.2267 / max 642.6341, expressed in 1792 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94755	21.8413	1782
94754	1.3854	807

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	96.29	gold quality
calcaneal tendon	UBERON:0003701	96.17	gold quality
gastrocnemius	UBERON:0001388	95.25	gold quality
muscle of leg	UBERON:0001383	95.04	gold quality
pancreas	UBERON:0001264	94.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.45	gold quality
endometrium	UBERON:0001295	94.38	gold quality
cortical plate	UBERON:0005343	93.95	gold quality
ganglionic eminence	UBERON:0004023	93.88	gold quality
adrenal tissue	UBERON:0018303	93.88	gold quality
corpus callosum	UBERON:0002336	93.72	gold quality
skeletal muscle tissue	UBERON:0001134	93.33	gold quality
muscle tissue	UBERON:0002385	92.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.88	gold quality
islet of Langerhans	UBERON:0000006	92.86	gold quality
ovary	UBERON:0000992	92.80	gold quality
rectum	UBERON:0001052	92.65	gold quality
left ovary	UBERON:0002119	92.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.46	gold quality
smooth muscle tissue	UBERON:0001135	92.38	gold quality
ventricular zone	UBERON:0003053	92.08	gold quality
right ovary	UBERON:0002118	91.82	gold quality
monocyte	CL:0000576	91.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.67	gold quality
substantia nigra	UBERON:0002038	91.67	gold quality
thoracic mammary gland	UBERON:0005200	91.67	gold quality
fallopian tube	UBERON:0003889	91.36	gold quality
leukocyte	CL:0000738	91.34	gold quality
tibial artery	UBERON:0007610	91.24	gold quality
popliteal artery	UBERON:0002250	91.22	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	2598.51
E-ANND-3	yes	9.87
E-GEOD-124858	no	321.49
E-MTAB-10596	no	180.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting TATDN1, 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-3134	100.00	66.43	777
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-3190-3P	97.61	66.95	1406

Literature-anchored findings (GeneRIF, showing 5)

• The data indicate that TATDN1 expression is associated with 95D cells’ higher potential of invasion and metastasis, and suggest that TATDN1 may be a potential prognostic factor and therapeutic target for non-small cell lung cancer. (PMID:26943769)
• TATDN1 enhanced the DDP-tolerance of NSCLC cells by upregulating TRIM66 expression via sponging miR-451, hinting a novel regulatory pathway of chemoresistance in DDP-tolerant NSCLC cells. (PMID:30481109)
• TATDN1 promotes the development and progression of breast cancer by targeting microRNA-140-3p. (PMID:31298381)
• LncRNA TATDN1 induces the progression of hepatocellular carcinoma via targeting miRNA-6089. (PMID:31378885)
• Human and bacterial TatD enzymes exhibit apurinic/apyrimidinic (AP) endonuclease activity. (PMID:36881763)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tatdn1	ENSDARG00000036924
mus_musculus	Tatdn1	ENSMUSG00000050891
rattus_norvegicus	Tatdn1	ENSRNOG00000047198
drosophila_melanogaster	CG3358	FBGN0033117

Paralogs (2): TATDN2 (ENSG00000157014), TATDN3 (ENSG00000203705)

Protein

Protein identifiers

Deoxyribonuclease TATDN1 — Q6P1N9 (reviewed: Q6P1N9)

Alternative names: DNA-(apurinic or apyrimidinic site) endonuclease TATDN1, Hepatocarcinoma high expression protein

All UniProt accessions (13): Q6P1N9, A0A0D9SGD3, E5RG17, E5RG62, E5RGF2, E5RH86, E5RI69, E5RID7, E5RJY6, E5RK70, G5EA19, H0YBX2, U3KQS5

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits 3’-5’ exonuclease and apurinic/apyrimidinic (AP) endonuclease activities (in vitro). Shows preferential AP endonuclease activity on dsDNA substrates and 3’-5’ exonuclease activity on ssDNA. Catalyzes decatenation of catenated kinetoplast DNA to produce separated linear DNA in vitro. Plays an important role in chromosomal segregation and cell cycle progression during eye development probably via its DNA decatenation activity.

Subcellular location. Nucleus.

Activity regulation. 3’-exonuclease activity is suppressed in presence of Ca(2+), Zn(2+) and Ni(2+).

Cofactor. Binds 2 divalent metal cations per subunit.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P1N9-1	1	yes
Q6P1N9-2	2

RefSeq proteins (5): NP_001139632, NP_001304818, NP_001304819, NP_001304820, NP_114415* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001130	TatD-like	Family
IPR018228	DNase_TatD-rel_CS	Conserved_site
IPR032466	Metal_Hydrolase	Homologous_superfamily
IPR050891	TatD-type_Hydrolase	Family

Pfam: PF01026

UniProt features (54 total): helix 18, binding site 11, strand 11, mutagenesis site 6, modified residue 2, turn 2, chain 1, disulfide bond 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2XIO	X-RAY DIFFRACTION	1.19
8EFG	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P1N9-F1	98.01	0.99

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 (11): 77; 222; 226; 112; 112; 118; 119; 149; 174; 175; 201

Post-translational modifications (2): 27, 46

Disulfide bonds (1): 198–226

Mutagenesis-validated functional residues (6):

Position	Phenotype
77	reduces ap endodeoxyribonuclease activity 10-fold. does not affect the exonuclease activity.
112	reduces ap endodeoxyribonuclease and 3’-exonuclease activities.
112	increases ap endodeoxyribonuclease and 3’-exonuclease activities.
119	severely reduced the ap endodeoxyribonuclease activity in double-stranded dna. reduced the 3’-exonuclease activity on ss
119	does not affect the ap endodeoxyribonuclease activity in double-stranded dna. reduced the 3’-exonuclease activity on ssd
222	does not affect either ap endodeoxyribonuclease or 3’-exonuclease activities.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, CREL_01, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOMF_EXONUCLEASE_ACTIVITY, ACEVEDO_LIVER_CANCER_UP, GOMF_DNA_ENDONUCLEASE_ACTIVITY, TGGAAA_NFAT_Q4_01, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, GOBP_DNA_METABOLIC_PROCESS, POS_RESPONSE_TO_HISTAMINE_DN, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_3_5_EXONUCLEASE_ACTIVITY, HAMAI_APOPTOSIS_VIA_TRAIL_UP

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

GO Molecular Function (7): DNA endonuclease activity (GO:0004520), 3’-5’-DNA exonuclease activity (GO:0008296), metal ion binding (GO:0046872), nuclease activity (GO:0004518), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788)

GO Cellular Component (3): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
nucleic acid metabolic process	1
endonuclease activity	1
DNA nuclease activity	1
3’-5’ exonuclease activity	1
DNA exonuclease activity, producing 5’-phosphomonoesters	1
cation binding	1
catalytic activity, acting on a nucleic acid	1
binding	1
catalytic activity	1
hydrolase activity	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TATDN1	TRIM66	O15016	565
TATDN1	RNF139	Q8WU17	423
TATDN1	KLHL22	Q53GT1	400
TATDN1	LIX1L	Q8IVB5	400
TATDN1	GSDMB	Q8TAX9	397
TATDN1	THUMPD2	Q9BTF0	396
TATDN1	GULP1	Q9UBP9	395
TATDN1	MTSS1	O43312	370
TATDN1	NDUFB1	O75438	357
TATDN1	ENDOG	Q14249	351
TATDN1	EXOSC5	Q9NQT4	348
TATDN1	MCRIP2	Q9BUT9	348
TATDN1	DCLRE1A	Q6PJP8	330
TATDN1	NDUFB9	Q9Y6M9	325
TATDN1	CLDND1	Q9NY35	321

IntAct

20 interactions, top by confidence:

A	B	Type	Score
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
XAF1	AKT1	psi-mi:“MI:0914”(association)	0.670
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640
HSD17B6	NME2P1	psi-mi:“MI:0914”(association)	0.530
CCT7	PEX7	psi-mi:“MI:0914”(association)	0.530
FBXO17	NMT2	psi-mi:“MI:0914”(association)	0.530
TATDN1	ARFGEF2	psi-mi:“MI:0915”(physical association)	0.400
HSPB2	TATDN1	psi-mi:“MI:0915”(physical association)	0.370
PDSS1	PCBP3	psi-mi:“MI:0914”(association)	0.350
TRMU	IFT56	psi-mi:“MI:0914”(association)	0.350
PDCL3	POTEF	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	BCKDK	psi-mi:“MI:0914”(association)	0.350
IL12RB1	ZNF185	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
	GLRX3	psi-mi:“MI:0914”(association)	0.350

BioGRID (58): TATDN1 (Affinity Capture-MS), ARFGAP2 (Co-fractionation), GART (Co-fractionation), IRF2BP1 (Co-fractionation), KIAA0368 (Co-fractionation), LONP1 (Co-fractionation), SH3PXD2B (Co-fractionation), TATDN1 (Co-fractionation), TATDN1 (Co-fractionation), TATDN1 (Co-fractionation), TATDN1 (Co-fractionation), TATDN1 (Co-fractionation), TATDN1 (Co-fractionation), TATDN1 (Co-fractionation), TATDN1 (Co-fractionation)

ESM2 similar proteins: A0A0U1WZ18, A3QK15, B9N1F9, D3ZVR9, E0CSI1, O70196, P00503, P00504, P05201, P08906, P33121, P33124, P40142, P50137, P50554, P54767, P61922, P78330, P80147, Q07346, Q14410, Q15124, Q1W377, Q28BL6, Q2KHU0, Q2KIG0, Q42472, Q42521, Q4R4D5, Q4R5L1, Q5R691, Q5RB83, Q5ZLG0, Q6P1N9, Q6P8M1, Q7TN78, Q80W40, Q86V21, Q8BZF8, Q8K183

Diamond homologs: A4WFX9, A7MQN1, A8ACY8, A8G8C4, B1JP69, B2VG45, B5XYH5, B7LTZ5, C4VAS3, C6C4V4, C6DI71, C9XTA5, D0KC77, D0Z9R0, D2TUZ4, D4GGR2, D4ICL5, D8MKW4, E0SLH6, E1SKR8, E3G381, E6WHK1, E8XYF5, O08343, P0AFQ7, P0AFQ8, P0AFQ9, P27859, P34220, P37545, P44718, P73335, Q0SZ31, Q148G4, Q503T5, Q640V9, Q6DAQ1, Q6GML7, Q6P1N9, Q6P8M1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chaperonin-mediated protein folding	5	68.3×	6e-07
Association of TriC/CCT with target proteins during biosynthesis	5	66.5×	6e-07
Protein folding	5	59.0×	8e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	5	19.1×	3e-04
protein stabilization	5	12.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1884 predictions. Top by Δscore:

Variant	Effect	Δscore
8:124495544:T:C	acceptor_gain	1.0000
8:124504270:CCAA:C	donor_gain	1.0000
8:124508601:AC:A	donor_gain	1.0000
8:124508602:CC:C	donor_gain	1.0000
8:124508686:TAT:T	acceptor_gain	1.0000
8:124508687:ATC:A	acceptor_loss	1.0000
8:124508688:TCTGC:T	acceptor_loss	1.0000
8:124508689:C:A	acceptor_loss	1.0000
8:124508689:C:CC	acceptor_gain	1.0000
8:124508696:A:AC	acceptor_gain	1.0000
8:124508696:A:C	acceptor_gain	1.0000
8:124511604:T:A	donor_gain	1.0000
8:124515744:A:AC	donor_gain	1.0000
8:124515745:C:CC	donor_gain	1.0000
8:124515879:GCACT:G	donor_loss	1.0000
8:124515880:CACTC:C	donor_loss	1.0000
8:124515881:ACTC:A	donor_loss	1.0000
8:124515882:CT:C	donor_loss	1.0000
8:124515883:TCAC:T	donor_loss	1.0000
8:124515884:CACCA:C	donor_loss	1.0000
8:124515885:A:AC	donor_gain	1.0000
8:124515885:ACC:A	donor_loss	1.0000
8:124515886:C:A	donor_loss	1.0000
8:124515886:C:CC	donor_gain	1.0000
8:124516026:CATAC:C	acceptor_gain	1.0000
8:124518878:TAAA:T	acceptor_gain	1.0000
8:124518882:C:CC	acceptor_gain	1.0000
8:124539285:GAG:G	donor_gain	1.0000
8:124539286:AGGTA:A	donor_loss	1.0000
8:124539287:GGTAA:G	donor_loss	1.0000

AlphaMissense

1980 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:124493853:T:A	R257S	0.999
8:124493853:T:G	R257S	0.999
8:124504344:G:C	H174D	0.999
8:124508633:G:C	H149D	0.999
8:124508626:C:G	R151P	0.998
8:124515779:C:G	R119P	0.998
8:124515787:A:C	D116E	0.998
8:124515787:A:T	D116E	0.998
8:124515788:T:A	D116V	0.998
8:124515788:T:C	D116G	0.998
8:124515788:T:G	D116A	0.998
8:124515887:C:G	D116H	0.998
8:124515898:T:A	E112V	0.998
8:124516004:G:C	H77D	0.998
8:124493854:C:G	R257T	0.997
8:124493948:A:G	C226R	0.997
8:124493951:A:G	W225R	0.997
8:124493951:A:T	W225R	0.997
8:124493953:G:T	P224H	0.997
8:124493956:G:T	A223E	0.997
8:124493958:A:C	D222E	0.997
8:124493958:A:T	D222E	0.997
8:124493959:T:A	D222V	0.997
8:124495472:C:G	D222H	0.997
8:124495474:G:A	T221I	0.997
8:124504276:A:C	N196K	0.997
8:124504276:A:T	N196K	0.997
8:124504336:A:C	F176L	0.997
8:124504336:A:T	F176L	0.997
8:124504338:A:G	F176L	0.997

dbSNP variants (sampled 300 via entrez): RS1000053857 (8:124491147 T>C), RS1000107221 (8:124495004 G>A), RS1000146168 (8:124537855 T>C), RS1000198114 (8:124538149 T>C), RS1000221315 (8:124503053 C>T), RS1000275898 (8:124532113 G>C), RS1000278197 (8:124488316 G>A), RS1000367721 (8:124533592 G>A), RS1000425431 (8:124526321 G>C), RS1000533108 (8:124497034 A>G), RS1000562563 (8:124494704 C>T), RS1000599371 (8:124489888 T>G), RS1000710995 (8:124531908 G>A,T), RS1000748603 (8:124527613 G>A,T), RS1000806508 (8:124515521 A>C)

Disease associations

OMIM: gene MIM:619364 | 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
GCST005851_14	Delirium	1.000000e-06
GCST007266_2	Adult asthma	3.000000e-07

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
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression, increases expression	3
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	affects expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
perfluoro-n-nonanoic acid	increases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Dimethyl Sulfoxide	affects expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
T-2 Toxin	increases expression	1
Thiram	increases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1
Valproic Acid	decreases expression	1
Aflatoxin M1	decreases expression	1
Antirheumatic Agents	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases expression, increases abundance	1
Volatile Organic Compounds	increases oxidation, affects cotreatment	1

Clinical trials (associated diseases)

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