DNTTIP1

Summary

DNTTIP1 (deoxynucleotidyltransferase terminal interacting protein 1, HGNC:16160) is a protein-coding gene on chromosome 20q13.12, encoding Deoxynucleotidyltransferase terminal-interacting protein 1 (Q9H147). Increases DNTT terminal deoxynucleotidyltransferase activity (in vitro).

DNTTIP1 binds DNA and enhances the activity of terminal deoxynucleotidyltransferase (TDT, or DNTT; MIM 187410), a DNA polymerase that catalyzes the polymerization of DNA in the absence of a DNA template (Yamashita et al., 2001 [PubMed 11473582]).

Source: NCBI Gene 116092 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_052951

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16160
Approved symbol	DNTTIP1
Name	deoxynucleotidyltransferase terminal interacting protein 1
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ447F3.4, Tdif1
Ensembl gene	ENSG00000101457
Ensembl biotype	protein_coding
OMIM	611388
Entrez	116092

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000372622, ENST00000415790, ENST00000435014, ENST00000449078, ENST00000456939, ENST00000467701, ENST00000857002, ENST00000857003, ENST00000857004, ENST00000857005

RefSeq mRNA: 1 — MANE Select: NM_052951 NM_052951

CCDS: CCDS13369

Canonical transcript exons

ENST00000372622 — 13 exons

Exon	Start	End
ENSE00000662410	45795345	45795443
ENSE00000845021	45791954	45792109
ENSE00001042269	45801074	45801142
ENSE00001042311	45809114	45809185
ENSE00001042390	45810885	45810940
ENSE00001042507	45801402	45801458
ENSE00001107988	45801999	45802057
ENSE00001107991	45803333	45803378
ENSE00001624771	45792677	45792747
ENSE00001636182	45793921	45794017
ENSE00003469467	45805306	45805366
ENSE00003488319	45805146	45805204
ENSE00003845772	45811057	45811418

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 94.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.2432 / max 293.7468, expressed in 1822 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184938	28.4056	1822
184939	3.2965	1526
184943	0.2540	116
184942	0.2526	83
184940	0.0181	5
184941	0.0165	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	94.89	gold quality
leukocyte	CL:0000738	94.73	gold quality
blood	UBERON:0000178	93.56	gold quality
gastrocnemius	UBERON:0001388	93.53	gold quality
rectum	UBERON:0001052	93.26	gold quality
muscle of leg	UBERON:0001383	93.22	gold quality
quadriceps femoris	UBERON:0001377	92.97	gold quality
nasal cavity epithelium	UBERON:0005384	92.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.67	gold quality
upper arm skin	UBERON:0004263	92.65	gold quality
granulocyte	CL:0000094	92.63	gold quality
vastus lateralis	UBERON:0001379	92.61	gold quality
tibialis anterior	UBERON:0001385	92.61	silver quality
skeletal muscle tissue	UBERON:0001134	92.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.21	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.13	gold quality
muscle tissue	UBERON:0002385	91.97	gold quality
mucosa of transverse colon	UBERON:0004991	91.85	gold quality
deltoid	UBERON:0001476	91.76	gold quality
kidney epithelium	UBERON:0004819	91.48	silver quality
transverse colon	UBERON:0001157	91.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.95	gold quality
lower esophagus	UBERON:0013473	90.92	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.86	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.75	gold quality
left testis	UBERON:0004533	90.59	gold quality
smooth muscle tissue	UBERON:0001135	90.47	gold quality
colon	UBERON:0001155	90.39	gold quality
biceps brachii	UBERON:0001507	90.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.22
E-ENAD-17	no	156.27

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2584.1	DNTTIP1	NFkappaB-related

JASPAR matrix evidence (PMIDs): PMID:23874396

miRNA regulators (miRDB)

17 targeting DNTTIP1, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-8086	97.21	64.13	331

Literature-anchored findings (GeneRIF, showing 8)

• The TdT binding, DNA binding and dimerization regions, and nuclear localization signal (NLS) in TdIF1, were identified. (PMID:17663723)
• During cell division, DNTTIP1 forms a complex with C14ORF43/MIDEAS and HDAC1/HDAC2. (PMID:21258344)
• During cell division, DNTTIP1 is part of the mitotic deacetylase complex MIDAC, which also contains C14ORF43/MIDEAS and HDAC1/HDAC2. (PMID:21258344)
• TdIF1 associates with the RAB20 promoter, and RAB20 gene transcription is reduced in TdIF1-knocked-down cells, suggesting that TdIF1 stimulates RAB20 gene transcription. (PMID:23874396)
• In luciferase assays, TdIF1 can up-regulate transcription activity of the promoters containing the TdIF1-binding sequences, and this effect is mainly through the palindrome 5’-TGCATG-3’. (PMID:25619743)
• Overexpressed deoxynucleotidyltransferase terminal interacting protein 1 (DNTTIP1) was observed in oral squamous cell carcinomas (OSCCs) in vitro and in vivo and was correlated positively with tumoral growth. (PMID:29855544)
• TdIF1-LSD1 Axis Regulates Epithelial-Mesenchymal Transition and Metastasis via Histone Demethylation of E-Cadherin Promoter in Lung Cancer. (PMID:35008676)
• DNTTIP1 promotes nasopharyngeal carcinoma metastasis via recruiting HDAC1 to DUSP2 promoter and activating ERK signaling pathway. (PMID:35689852)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ube2c	ENSDARG00000101618
mus_musculus	Dnttip1	ENSMUSG00000017299
rattus_norvegicus	Dnttip1	ENSRNOG00000014933
caenorhabditis_elegans		WBGENE00011964

Protein

Protein identifiers

Deoxynucleotidyltransferase terminal-interacting protein 1 — Q9H147 (reviewed: Q9H147)

Alternative names: Terminal deoxynucleotidyltransferase-interacting factor 1

All UniProt accessions (5): Q9H147, F2Z2A4, H0Y501, H7C1J2, H7C1M5

UniProt curated annotations — full annotation on UniProt →

Function. Increases DNTT terminal deoxynucleotidyltransferase activity (in vitro). Also acts as a transcriptional regulator, binding to the consensus sequence 5’-GNTGCATG-3’ following an AT-tract. Associates with RAB20 promoter and positively regulates its transcription. Binds DNA and nucleosomes; may recruit HDAC1 complexes to nucleosomes or naked DNA.

Subunit / interactions. Monomer and homodimer. A minor proportion may form homotrimers. Interacts with ZNF541. Interacts with the terminal deoxynucleotidyltransferase DNTT. Interacts with TRERF1. Identified in a histone deacetylase complex that contains DNTTIP1, HDAC1 and MIDEAS; this complex assembles into a tetramer that contains four copies of each protein chain. Component of a histone deacetylase complex containing DNTTIP1, ZNF541, HDAC1 and HDAC2. Identified in a complex with KCTD19, HDAC1, HDAC2 and ZNF541.

Subcellular location. Nucleus.

Domain organisation. The N-terminal domain mediates dimerization. The C-terminal domain mediates interaction with DNA and nucleosomes. It contains a HTH motif that mediates recognition of the consensus sequence.

RefSeq proteins (1): NP_443183* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026064	TdIF1	Family
IPR041384	DNTTIP1_dimer	Domain
IPR049121	TdIF1_C	Domain

Pfam: PF18192, PF21229

UniProt features (28 total): helix 9, strand 4, turn 4, region of interest 4, DNA-binding region 2, chain 1, sequence variant 1, short sequence motif 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4D6K	X-RAY DIFFRACTION	2.1
9R4I	ELECTRON MICROSCOPY	2.92
6Z2J	ELECTRON MICROSCOPY	4
6Z2K	ELECTRON MICROSCOPY	4.5
2MWI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H147-F1	69.24	0.27

Functional residue map

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

Post-translational modifications (1): 161

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription

MSigDB gene sets: 99 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, ATF_B, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, AP2_Q3, FOXD3_01, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, ATF1_Q6, CREB_Q2_01, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_EMBRYO_DEVELOPMENT, GOBP_REGULATION_OF_EMBRYONIC_DEVELOPMENT, CREBP1CJUN_01, GRADE_COLON_AND_RECTAL_CANCER_UP, GOMF_CHROMATIN_BINDING, CREB_01

GO Biological Process (0):

GO Molecular Function (4): DNA binding (GO:0003677), nucleosome binding (GO:0031491), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (5): histone deacetylase complex (GO:0000118), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of CDH1 Gene Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
intracellular membraneless organelle	2
nucleic acid binding	1
chromatin binding	1
protein-containing complex binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNTTIP1	DNTT	P04053	951
DNTTIP1	HDAC1	Q13547	923
DNTTIP1	MIDEAS	Q6PJG2	884
DNTTIP1	TRERF1	Q96PN7	864
DNTTIP1	ZNF541	Q9H0D2	711
DNTTIP1	KCTD19	Q17RG1	664
DNTTIP1	F5H6H0	F5H6H0	649
DNTTIP1	HDAC2	Q92769	614
DNTTIP1	WFDC3	Q8IUB2	504
DNTTIP1	DNTTIP2	Q5QJE6	503
DNTTIP1	RELA	Q04206	486
DNTTIP1	WFDC13	Q8IUB5	458
DNTTIP1	MTA1	Q13330	455
DNTTIP1	SLCO6A1	Q86UG4	448
DNTTIP1	SPINT4	Q6UDR6	435

IntAct

152 interactions, top by confidence:

A	B	Type	Score
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
DNTTIP1	HDAC1	psi-mi:“MI:0914”(association)	0.880
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
TRERF1	HDAC1	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
HOMEZ	DNTTIP1	psi-mi:“MI:0915”(physical association)	0.560
MFAP1	DNTTIP1	psi-mi:“MI:0915”(physical association)	0.560
	DNTTIP1	psi-mi:“MI:0915”(physical association)	0.560
DNTTIP1	PICK1	psi-mi:“MI:0915”(physical association)	0.560
MAGEA6	DNTTIP1	psi-mi:“MI:0915”(physical association)	0.560
EAF1	DNTTIP1	psi-mi:“MI:0915”(physical association)	0.560
ANP32B	DNTTIP1	psi-mi:“MI:0915”(physical association)	0.560
HMBOX1	DNTTIP1	psi-mi:“MI:0915”(physical association)	0.560
DNTTIP1	A2M	psi-mi:“MI:0915”(physical association)	0.560
DNTTIP1	DMWD	psi-mi:“MI:0915”(physical association)	0.560
DNTTIP1	DNM2	psi-mi:“MI:0915”(physical association)	0.560
DNTTIP1	TOR1A	psi-mi:“MI:0915”(physical association)	0.560
DNTTIP1		psi-mi:“MI:0915”(physical association)	0.560
DNTTIP1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
DNTTIP1	TSC1	psi-mi:“MI:0915”(physical association)	0.560
DNTTIP1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (133): DNTTIP1 (Two-hybrid), DNTTIP1 (Affinity Capture-MS), DNTTIP1 (Affinity Capture-MS), EIF2S1 (Co-fractionation), ELMSAN1 (Co-fractionation), WIBG (Co-fractionation), DNTTIP1 (Synthetic Lethality), DNTTIP1 (Proximity Label-MS), DNTTIP1 (Proximity Label-MS), DNTTIP1 (Proximity Label-MS), DNTTIP1 (Affinity Capture-MS), DNTTIP1 (Affinity Capture-MS), DNTTIP1 (Affinity Capture-MS), DNTTIP1 (Affinity Capture-MS), DNTTIP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A088MLT8, A0JNC2, A2AQ25, A6H7A8, B3KU38, B5DF41, E1BEQ5, E9PSK7, O15079, O60271, Q157S1, Q3MHV6, Q4VCS5, Q58A65, Q5F3B1, Q5R595, Q5T5P2, Q62739, Q68ED7, Q68FF7, Q7KW14, Q7PQ25, Q80TM6, Q80U23, Q86YP4, Q8CHY6, Q8CI08, Q8IY63, Q8ND83, Q8TEK3, Q8VHG2, Q8VHI6, Q8VHR5, Q8WXI9, Q920B0, Q921D9, Q96QF0, Q99LB0, Q9C0H9, Q9DCB4

Diamond homologs: A6H7A8, Q5R595, Q91Y53, Q99LB0, Q9H147

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 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
NuRD complex assembly	6	11.6×	3e-03
Negative Regulation of CDH1 Gene Transcription	7	11.5×	1e-03
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	5	11.5×	4e-03
Interaction of NuRD complexes with transcription factors	6	10.4×	4e-03
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	5	10.4×	6e-03
HDACs deacetylate histones	6	9.9×	4e-03
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	6	9.7×	4e-03
NoRC negatively regulates rRNA expression	6	8.6×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
somatic stem cell population maintenance	5	11.8×	3e-03
transcription by RNA polymerase II	10	6.7×	4e-04
chromatin remodeling	9	6.2×	1e-03
negative regulation of apoptotic process	11	3.6×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1243 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45792744:CAAGG:C	donor_loss	1.0000
20:45792747:GGT:G	donor_loss	1.0000
20:45792748:G:GC	donor_loss	1.0000
20:45792748:G:GG	donor_gain	1.0000
20:45792749:T:A	donor_loss	1.0000
20:45793912:T:A	acceptor_gain	1.0000
20:45793916:T:G	acceptor_gain	1.0000
20:45793916:T:TA	acceptor_gain	1.0000
20:45793919:A:AG	acceptor_gain	1.0000
20:45793920:G:GA	acceptor_gain	1.0000
20:45793920:GT:G	acceptor_gain	1.0000
20:45793920:GTT:G	acceptor_gain	1.0000
20:45793920:GTTT:G	acceptor_gain	1.0000
20:45793920:GTTTC:G	acceptor_gain	1.0000
20:45794016:AGG:A	donor_loss	1.0000
20:45794017:GGTGA:G	donor_loss	1.0000
20:45794018:G:GC	donor_loss	1.0000
20:45794019:T:A	donor_loss	1.0000
20:45795334:T:TA	acceptor_gain	1.0000
20:45795343:A:AG	acceptor_gain	1.0000
20:45795344:G:GC	acceptor_gain	1.0000
20:45795344:GT:G	acceptor_gain	1.0000
20:45795344:GTT:G	acceptor_gain	1.0000
20:45795344:GTTC:G	acceptor_gain	1.0000
20:45795344:GTTCT:G	acceptor_gain	1.0000
20:45795439:AGCAG:A	donor_loss	1.0000
20:45795440:GCAG:G	donor_gain	1.0000
20:45795440:GCAGG:G	donor_loss	1.0000
20:45795441:CAGG:C	donor_loss	1.0000
20:45795442:AGG:A	donor_loss	1.0000

AlphaMissense

2143 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45793941:C:T	S66F	1.000
20:45793950:T:C	L69P	1.000
20:45793953:T:A	L70H	1.000
20:45793953:T:C	L70P	1.000
20:45793965:T:C	L74P	1.000
20:45795436:T:C	L122P	1.000
20:45805146:T:A	W202R	1.000
20:45805146:T:C	W202R	1.000
20:45805148:G:C	W202C	1.000
20:45805148:G:T	W202C	1.000
20:45805179:T:C	F213L	1.000
20:45805180:T:C	F213S	1.000
20:45805181:T:A	F213L	1.000
20:45805181:T:G	F213L	1.000
20:45805183:T:A	V214E	1.000
20:45805186:T:C	L215S	1.000
20:45805188:G:A	G216R	1.000
20:45805188:G:C	G216R	1.000
20:45805189:G:A	G216E	1.000
20:45805189:G:T	G216V	1.000
20:45805197:G:C	A219P	1.000
20:45805198:C:A	A219D	1.000
20:45805200:A:G	N220D	1.000
20:45805201:A:T	N220I	1.000
20:45805202:C:A	N220K	1.000
20:45805202:C:G	N220K	1.000
20:45805203:A:G	K221E	1.000
20:45805204:A:T	K221I	1.000
20:45805306:A:C	K221N	1.000
20:45805306:A:T	K221N	1.000

dbSNP variants (sampled 300 via entrez): RS1000000152 (20:45802650 G>A), RS1000395850 (20:45794033 G>A,T), RS1000676470 (20:45792716 C>G,T), RS1000728558 (20:45792447 C>G,T), RS1000846401 (20:45795119 C>A,T), RS1000981631 (20:45794952 C>T), RS1001047083 (20:45805433 A>G,T), RS1001117166 (20:45811909 A>C,G), RS1001121176 (20:45803225 A>G), RS1001124466 (20:45806096 C>G), RS1001280343 (20:45810823 G>A,C), RS1001780430 (20:45795746 C>T), RS1002229203 (20:45793307 A>G,T), RS1002300101 (20:45799827 G>T), RS1002759023 (20:45799475 G>A)

Disease associations

OMIM: gene MIM:611388 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004599_211	Mean platelet volume	3.000000e-15
GCST009195_6	Temporal pole volume	4.000000e-06
GCST90002395_599	Mean platelet volume	1.000000e-30

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	affects expression	1
abrine	increases expression	1
Temozolomide	decreases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Atrazine	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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