TATDN2

Summary

TATDN2 (TatD DNase domain containing 2, HGNC:28988) is a protein-coding gene on chromosome 3p25.3, encoding 3’-5’ RNA nuclease TATDN2 (Q93075). Mg(2+)-dependent 3’RNA exonuclease and endonuclease that resolves R-loops via specific degradation of R-loop RNA structure.

Predicted to enable metal ion binding activity and nuclease activity. Predicted to be located in nucleoplasm.

Source: NCBI Gene 9797 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_014760

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28988
Approved symbol	TATDN2
Name	TatD DNase domain containing 2
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0218
Ensembl gene	ENSG00000157014
Ensembl biotype	protein_coding
OMIM	619330
Entrez	9797

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000287652, ENST00000426850, ENST00000448281, ENST00000496355

RefSeq mRNA: 1 — MANE Select: NM_014760 NM_014760

CCDS: CCDS33698

Canonical transcript exons

ENST00000448281 — 8 exons

Exon	Start	End
ENSE00001029764	10249195	10249614
ENSE00001663638	10248459	10249067
ENSE00001684719	10278885	10279063
ENSE00001939292	10279221	10281218
ENSE00003695924	10278279	10278462
ENSE00003698374	10270131	10271015
ENSE00003698418	10276361	10276488
ENSE00003701850	10260137	10260670

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 94.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.4449 / max 327.2458, expressed in 1799 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35305	14.7694	1796
35306	0.6356	390
35307	0.0399	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	94.10	silver quality
olfactory bulb	UBERON:0002264	93.97	silver quality
cortical plate	UBERON:0005343	92.34	gold quality
granulocyte	CL:0000094	92.29	gold quality
middle temporal gyrus	UBERON:0002771	92.16	gold quality
thymus	UBERON:0002370	91.86	gold quality
cartilage tissue	UBERON:0002418	90.75	gold quality
ganglionic eminence	UBERON:0004023	89.96	gold quality
gingival epithelium	UBERON:0001949	89.84	gold quality
lymph node	UBERON:0000029	89.70	gold quality
prefrontal cortex	UBERON:0000451	89.43	gold quality
left ovary	UBERON:0002119	89.39	gold quality
leukocyte	CL:0000738	89.38	gold quality
right ovary	UBERON:0002118	89.26	gold quality
islet of Langerhans	UBERON:0000006	89.20	gold quality
monocyte	CL:0000576	89.09	gold quality
mononuclear cell	CL:0000842	89.09	gold quality
endometrium epithelium	UBERON:0004811	89.08	gold quality
lower esophagus mucosa	UBERON:0035834	89.01	gold quality
right frontal lobe	UBERON:0002810	88.83	gold quality
left lobe of thyroid gland	UBERON:0001120	88.62	gold quality
ventricular zone	UBERON:0003053	88.53	gold quality
blood	UBERON:0000178	88.51	gold quality
right lobe of thyroid gland	UBERON:0001119	88.18	gold quality
spleen	UBERON:0002106	88.17	gold quality
cingulate cortex	UBERON:0003027	88.07	gold quality
gingiva	UBERON:0001828	87.97	gold quality
amygdala	UBERON:0001876	87.96	gold quality
ectocervix	UBERON:0012249	87.96	gold quality
neocortex	UBERON:0001950	87.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting TATDN2, 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-4682	100.00	68.89	1258
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-653-3P	98.31	67.71	1542

Literature-anchored findings (GeneRIF, showing 2)

• Describes transcription of the non-coding RNA GHRLOS, including potential read-through transcription from the TATDN2 locus. (PMID:18954468)
• TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells. (PMID:37953292)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tatdn2	ENSDARG00000070618
mus_musculus	Tatdn2	ENSMUSG00000056952
rattus_norvegicus	Tatdn2	ENSRNOG00000042482
caenorhabditis_elegans		WBGENE00012496
caenorhabditis_elegans		WBGENE00012562

Paralogs (2): TATDN1 (ENSG00000147687), TATDN3 (ENSG00000203705)

Protein

Protein identifiers

3’-5’ RNA nuclease TATDN2 — Q93075 (reviewed: Q93075)

Alternative names: TatD DNase domain containing 2

All UniProt accessions (2): Q93075, H7BZJ2

UniProt curated annotations — full annotation on UniProt →

Function. Mg(2+)-dependent 3’RNA exonuclease and endonuclease that resolves R-loops via specific degradation of R-loop RNA structure. Shows no activity against D-loop and minimal activity against the RNA strand of an RNA-DNA hybrid duplex oligomer. Has no 3’ or 5’ exonuclease activity, no uracil glycosylase activity, and no 5’ flap endonuclease activity on DNA substrates. May have a role in maintaining genomic stability through its role in R-loop resolution.

Subcellular location. Nucleus.

Cofactor. No activity in the presence of Ca(2+). Mild activity in the presence of Mn(2+).

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

RefSeq proteins (1): NP_055575* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF01026

UniProt features (26 total): binding site 7, region of interest 6, compositionally biased region 6, sequence variant 3, mutagenesis site 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93075-F1	59.80	0.36

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): 499; 501; 593; 593; 630; 655; 707

Mutagenesis-validated functional residues (3):

Position	Phenotype
593	completely abrogates r-loop rna exonuclease activity. decreases binding to r-loop.
705	completely abrogates r-loop rna exonuclease activity.
707	decreases r-loop rna exonuclease activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-2262752	Cellular responses to stress
R-HSA-381070	IRE1alpha activates chaperones
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 102 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOMF_NUCLEASE_ACTIVITY, MORF_HDAC1, MORF_UBE2N, PUJANA_CHEK2_PCC_NETWORK, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOMF_EXONUCLEASE_ACTIVITY, GCM_ACTG1, DURCHDEWALD_SKIN_CARCINOGENESIS_DN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, YOSHIMURA_MAPK8_TARGETS_DN, MORF_ANP32B, KIM_ALL_DISORDERS_OLIGODENDROCYTE_NUMBER_CORR_UP, JAZAERI_BREAST_CANCER_BRCA1_VS_BRCA2_UP

GO Biological Process (0):

GO Molecular Function (5): exonuclease activity (GO:0004527), metal ion binding (GO:0046872), nuclease activity (GO:0004518), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788)

GO Cellular Component (2): nucleoplasm (GO:0005654), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
IRE1alpha activates chaperones	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclease activity	1
hydrolase activity, acting on ester bonds	1
cation binding	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1
hydrolase activity	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TATDN2	CCDC174	Q6PII3	595
TATDN2	PRRT3	Q5FWE3	570
TATDN2	MTFR1L	Q9H019	570
TATDN2	A0A087WY73	A0A087WY73	509
TATDN2	IRAK2	O43187	491
TATDN2	VWA5B1	Q5TIE3	483
TATDN2	UBE2L5	A0A1B0GUS4	480
TATDN2	MBOAT4	Q96T53	479
TATDN2	MGAT4B	Q9UQ53	450
TATDN2	FANCD2OS	Q96PS1	446
TATDN2	PPP1R35	Q8TAP8	445
TATDN2	SLC12A8	A0AV02	440
TATDN2	XKR5	Q6UX68	437
TATDN2	SUPV3L1	Q8IYB8	437
TATDN2	JAGN1	Q8N5M9	418

IntAct

14 interactions, top by confidence:

A	B	Type	Score
SPACA1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
CCNJL	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
NAGK	ZBTB43	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SPACA1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CCT2	WDR91	psi-mi:“MI:0914”(association)	0.350
ISCA1	BACH1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
TNIK	TATDN2	psi-mi:“MI:0915”(physical association)	0.000
TATDN2		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): TATDN2 (Affinity Capture-RNA), TATDN2 (Affinity Capture-RNA), TATDN2 (Affinity Capture-MS), TATDN2 (Affinity Capture-MS), TATDN2 (Affinity Capture-MS), TATDN2 (Affinity Capture-MS), TATDN2 (Affinity Capture-MS), TATDN2 (Affinity Capture-MS), TATDN2 (Affinity Capture-MS), TATDN2 (Affinity Capture-MS), TATDN2 (Affinity Capture-RNA), TATDN2 (Affinity Capture-RNA), TATDN2 (Affinity Capture-MS), TATDN2 (Affinity Capture-MS), TATDN2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A6NP61, A8T6P4, C0SPG1, C3VD30, F1N4E5, K7SGN7, O35144, O35253, O70240, O88406, O88566, Q15554, Q1XFL1, Q3ZC82, Q4KLH3, Q5HZN9, Q5JTV8, Q5PQX1, Q5R7A3, Q62315, Q68DK7, Q6P1H6, Q6PDM1, Q6PG95, Q6ZPF3, Q76N89, Q7T3T8, Q7T3T9, Q7T3U0, Q7TNY7, Q7TP65, Q7TSX9, Q80SU3, Q80VM8, Q86XL3, Q8IVF5, Q8K3I4

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2219 predictions. Top by Δscore:

Variant	Effect	Δscore
3:10260667:AAAGG:A	donor_loss	1.0000
3:10260668:AAG:A	donor_gain	1.0000
3:10260668:AAGG:A	donor_loss	1.0000
3:10260669:AGG:A	donor_loss	1.0000
3:10260670:GGT:G	donor_loss	1.0000
3:10260671:G:GA	donor_loss	1.0000
3:10260671:GTGA:G	donor_loss	1.0000
3:10260672:T:A	donor_loss	1.0000
3:10276459:G:GG	donor_gain	1.0000
3:10276520:A:T	donor_gain	1.0000
3:10276538:TC:T	donor_gain	1.0000
3:10278275:CCA:C	acceptor_loss	1.0000
3:10278277:A:AG	acceptor_gain	1.0000
3:10278277:A:G	acceptor_loss	1.0000
3:10278277:AG:A	acceptor_gain	1.0000
3:10278278:G:GA	acceptor_gain	1.0000
3:10278278:G:GC	acceptor_loss	1.0000
3:10278278:G:GG	acceptor_gain	1.0000
3:10278278:GG:G	acceptor_gain	1.0000
3:10278278:GGC:G	acceptor_gain	1.0000
3:10278278:GGCA:G	acceptor_gain	1.0000
3:10278278:GGCAT:G	acceptor_gain	1.0000
3:10278458:GCCAG:G	donor_gain	1.0000
3:10278462:GGTA:G	donor_loss	1.0000
3:10278462:GGTAA:G	donor_loss	1.0000
3:10278463:GT:G	donor_loss	1.0000
3:10278880:TCCA:T	acceptor_loss	1.0000
3:10278882:CAG:C	acceptor_loss	1.0000
3:10278883:A:C	acceptor_loss	1.0000
3:10278883:A:T	acceptor_loss	1.0000

AlphaMissense

5014 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:10270683:C:G	H501D	1.000
3:10270872:C:G	H564D	1.000
3:10270874:C:A	H564Q	1.000
3:10270874:C:G	H564Q	1.000
3:10270960:A:T	E593V	1.000
3:10270965:G:C	G595R	1.000
3:10276415:C:G	H630D	1.000
3:10276422:G:C	R632P	1.000
3:10278431:A:T	E705V	1.000
3:10278437:A:T	D707V	1.000
3:10270677:C:G	H499D	0.999
3:10270679:T:A	H499Q	0.999
3:10270679:T:G	H499Q	0.999
3:10270680:T:C	C500R	0.999
3:10270681:G:A	C500Y	0.999
3:10270682:T:G	C500W	0.999
3:10270685:C:A	H501Q	0.999
3:10270685:C:G	H501Q	0.999
3:10270735:T:C	F518S	0.999
3:10270759:T:C	F526S	0.999
3:10270770:T:C	F530L	0.999
3:10270771:T:C	F530S	0.999
3:10270772:T:A	F530L	0.999
3:10270772:T:G	F530L	0.999
3:10270779:T:C	C533R	0.999
3:10270783:T:A	I534N	0.999
3:10270824:T:A	W548R	0.999
3:10270824:T:C	W548R	0.999
3:10270863:T:C	F561L	0.999
3:10270865:T:A	F561L	0.999

dbSNP variants (sampled 300 via entrez): RS1000046008 (3:10267575 G>A), RS1000081783 (3:10266601 A>G), RS1000161179 (3:10248758 G>A,C), RS1000222636 (3:10273438 T>C), RS1000334155 (3:10254023 G>C), RS1000354590 (3:10259805 G>A), RS1000386754 (3:10254194 A>G), RS1000455914 (3:10279272 G>T), RS1000558530 (3:10272262 G>A), RS1000569520 (3:10249928 G>C), RS1000581076 (3:10265905 G>A,T), RS1000637856 (3:10248967 G>A,T), RS1000647466 (3:10267384 A>G), RS1000689207 (3:10254882 T>A), RS1000739197 (3:10277699 C>G,T)

Disease associations

OMIM: gene MIM:619330 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004521_106	Autism spectrum disorder or schizophrenia	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	2
sodium arsenite	affects expression, decreases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
diethyl maleate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Coumestrol	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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