RTF2

Summary

RTF2 (replication termination factor 2, HGNC:15890) is a protein-coding gene on chromosome 20q13.31, encoding Replication termination factor 2 (Q9BY42). Replication termination factor which is a component of the elongating replisome. It is a common-essential gene (DepMap: required in 98.4% of cancer cell lines).

Enables DNA binding activity. Involved in cellular response to hydroxyurea and regulation of DNA stability. Located in replication fork.

Source: NCBI Gene 51507 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 30 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_016407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15890
Approved symbol	RTF2
Name	replication termination factor 2
Location	20q13.31
Locus type	gene with protein product
Status	Approved
Aliases	HSPC164, CDAO5
Ensembl gene	ENSG00000022277
Ensembl biotype	protein_coding
Entrez	51507

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000023939, ENST00000357348, ENST00000395881, ENST00000449062, ENST00000466260, ENST00000477485, ENST00000477573, ENST00000484084, ENST00000487211, ENST00000886933, ENST00000886934, ENST00000886935, ENST00000886936, ENST00000886937, ENST00000886938, ENST00000923345, ENST00000923346

RefSeq mRNA: 4 — MANE Select: NM_016407 NM_001283035, NM_001283036, NM_001283037, NM_016407

CCDS: CCDS13453, CCDS63316, CCDS63317

Canonical transcript exons

ENST00000357348 — 9 exons

Exon	Start	End
ENSE00000662891	56476985	56477124
ENSE00001523173	56468627	56468766
ENSE00001613435	56518087	56519449
ENSE00001691939	56513315	56513428
ENSE00001723641	56516935	56516989
ENSE00001771707	56484111	56484189
ENSE00003675632	56474678	56474771
ENSE00003686251	56473301	56473395
ENSE00003786345	56517106	56517201

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.3246 / max 2592.6961, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185430	59.9481	1822
185439	0.1801	88
185437	0.0822	53
185436	0.0464	24
185435	0.0291	10
185440	0.0207	11
185438	0.0180	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	98.14	gold quality
calcaneal tendon	UBERON:0003701	97.85	gold quality
spinal cord	UBERON:0002240	97.42	gold quality
monocyte	CL:0000576	97.21	gold quality
mononuclear cell	CL:0000842	97.07	gold quality
popliteal artery	UBERON:0002250	97.07	gold quality
tibial artery	UBERON:0007610	97.07	gold quality
leukocyte	CL:0000738	97.06	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.99	gold quality
lower esophagus	UBERON:0013473	96.98	gold quality
muscle of leg	UBERON:0001383	96.96	gold quality
gastrocnemius	UBERON:0001388	96.91	gold quality
anterior cingulate cortex	UBERON:0009835	96.91	gold quality
right frontal lobe	UBERON:0002810	96.87	gold quality
cingulate cortex	UBERON:0003027	96.86	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.82	gold quality
aorta	UBERON:0000947	96.81	gold quality
descending thoracic aorta	UBERON:0002345	96.75	gold quality
ganglionic eminence	UBERON:0004023	96.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.72	gold quality
prefrontal cortex	UBERON:0000451	96.64	gold quality
thoracic aorta	UBERON:0001515	96.62	gold quality
caudate nucleus	UBERON:0001873	96.61	gold quality
ascending aorta	UBERON:0001496	96.58	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.54	gold quality
left coronary artery	UBERON:0001626	96.52	gold quality
granulocyte	CL:0000094	96.47	gold quality
right coronary artery	UBERON:0001625	96.46	gold quality
tibial nerve	UBERON:0001323	96.40	gold quality
adenohypophysis	UBERON:0002196	96.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting RTF2, 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-8073	99.86	65.21	1118
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-625-3P	97.32	66.55	554
HSA-MIR-5694	97.06	67.70	682
HSA-MIR-4522	95.76	66.23	742

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• The results establish that RTF2 removal is a key determinant for the ability of cells to manage replication stress and maintain genome integrity. (PMID:29290612)
• Loss of the Nuclear Protein RTF2 Enhances Influenza Virus Replication. (PMID:32878895)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rtf2	ENSDARG00000040607
mus_musculus	Rtf2	ENSMUSG00000027502
rattus_norvegicus	Rtfdc1	ENSRNOG00000005083
drosophila_melanogaster	CG6443	FBGN0032290
caenorhabditis_elegans	tads-1	WBGENE00007217

Protein

Protein identifiers

Replication termination factor 2 — Q9BY42 (reviewed: Q9BY42)

Alternative names: Replication termination factor 2 domain-containing protein 1

All UniProt accessions (4): A0A0A0MQR2, A2A2L5, A2A2L6, Q9BY42

UniProt curated annotations — full annotation on UniProt →

Function. Replication termination factor which is a component of the elongating replisome. Required for ATR pathway signaling upon DNA damage and has a positive activity during DNA replication. Might function to facilitate fork pausing at replication fork barriers like the rDNA. May be globally required to stimulate ATR signaling after the fork stalls or encounters a lesion. Interacts with nascent DNA.

Subunit / interactions. Interacts with DDI2; probably also interacts with DDI1.

Subcellular location. Chromosome.

Post-translational modifications. Undergoes proteasomal degradation, via DDI1 and DDI2. Removal from stalled replisomes and degradation are required for genome stability.

Similarity. Belongs to the rtf2 family.

RefSeq proteins (4): NP_001269964, NP_001269965, NP_001269966, NP_057491* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006735	Rtf2	Family
IPR027799	Rtf2_RING-finger	Domain

Pfam: PF04641

UniProt features (13 total): sequence conflict 6, compositionally biased region 2, sequence variant 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY42-F1	73.24	0.28

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): 287

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, ODONNELL_TARGETS_OF_MYC_AND_TFRC_UP, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GRADE_COLON_AND_RECTAL_CANCER_UP, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_NUCLEOLUS, SCGGAAGY_ELK1_02, NIKOLSKY_BREAST_CANCER_20Q12_Q13_AMPLICON, LIU_NASOPHARYNGEAL_CARCINOMA, MARTENS_BOUND_BY_PML_RARA_FUSION, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, GOBP_RESPONSE_TO_HYDROXYUREA, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, KUMAR_AUTOPHAGY_NETWORK, DIDO1_TARGET_GENES

GO Biological Process (3): cellular response to hydroxyurea (GO:0072711), regulation of DNA stability (GO:0097752), mitotic DNA replication termination (GO:1902979)

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), replication fork (GO:0005657), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to hydroxyurea	1
cellular response to nitrogen compound	1
regulation of biological quality	1
nuclear DNA replication termination	1
mitotic DNA replication	1
mitotic cell cycle process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
chromosome	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

778 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RTF2	RTF1	Q92541	739
RTF2	RPAP2	Q8IXW5	621
RTF2	ICA1L	Q8NDH6	561
RTF2	DDI2	Q5TDH0	545
RTF2	SNX32	Q86XE0	542
RTF2	LYG1	Q8N1E2	542
RTF2	YJU2B	P13994	499
RTF2	DDI1	Q8WTU0	496
RTF2	FAM209A	Q5JX71	480
RTF2	IFT70A	Q86WT1	476
RTF2	TOM1L2	Q6ZVM7	461
RTF2	SDE2	Q6IQ49	452
RTF2	EPM2AIP1	Q7L775	448
RTF2	RBM25	P49756	444
RTF2	TIPIN	Q9BVW5	441

IntAct

38 interactions, top by confidence:

A	B	Type	Score
APBA3	DUSP11	psi-mi:“MI:0914”(association)	0.530
BBOX1	ITPRID2	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
TCEAL1	CHEK1	psi-mi:“MI:0914”(association)	0.530
RTF2	FLNC	psi-mi:“MI:0915”(physical association)	0.500
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
RTF2	OGT	psi-mi:“MI:0915”(physical association)	0.400
RTF2	PAPD5	psi-mi:“MI:0915”(physical association)	0.400
RTF2	PTGER4	psi-mi:“MI:0915”(physical association)	0.370
SPRY2	RTF2	psi-mi:“MI:0915”(physical association)	0.370
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
NCBP3	RSL1D1	psi-mi:“MI:0914”(association)	0.350
TEX28	NBAS	psi-mi:“MI:0914”(association)	0.350
TMEM184A	NRDC	psi-mi:“MI:0914”(association)	0.350
MEOX2	CHMP2A	psi-mi:“MI:0914”(association)	0.350
RTF2	FLNB	psi-mi:“MI:0914”(association)	0.350
ZIC2	EEF1A2	psi-mi:“MI:0914”(association)	0.350
BBS1	SHTN1	psi-mi:“MI:0914”(association)	0.350
ZBTB2	SHTN1	psi-mi:“MI:0914”(association)	0.350
MND1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
MILR1	SBNO1	psi-mi:“MI:0914”(association)	0.350
RABGGTA	PALM3	psi-mi:“MI:0914”(association)	0.350
KDM4B	AP3B1	psi-mi:“MI:0914”(association)	0.350
KIFBP	STK25	psi-mi:“MI:0914”(association)	0.350
CES2	PPP1R12A	psi-mi:“MI:0914”(association)	0.350

BioGRID (91): RTFDC1 (Affinity Capture-MS), RTFDC1 (Affinity Capture-MS), RTFDC1 (Affinity Capture-MS), RTFDC1 (Affinity Capture-MS), ABL1 (Co-fractionation), CBS (Co-fractionation), CTPS1 (Co-fractionation), DDX17 (Co-fractionation), LARS (Co-fractionation), PIN4 (Co-fractionation), TRMT1 (Co-fractionation), OGT (Affinity Capture-MS), PAPD5 (Affinity Capture-MS), RTFDC1 (Affinity Capture-MS), RTFDC1 (Affinity Capture-MS)

ESM2 similar proteins: A2XIP9, A5GFW7, B1WB17, B4FGS2, E1C760, E7EXT2, F7AEX0, O15541, O59800, P0CR50, P0CR51, P28518, P35251, P35600, P35601, P35728, P52012, Q0VCR1, Q10154, Q21755, Q28E45, Q2R2B4, Q3LSS0, Q3T1J8, Q4P400, Q4R594, Q5AX35, Q5AXT6, Q5EAW4, Q5FVF1, Q5R9P9, Q5ZJN1, Q640E9, Q67ER4, Q6C3L4, Q70Z53, Q75LU5, Q810J8, Q8BP78, Q8IZP6

Diamond homologs: A5GFW7, Q0VCR1, Q10154, Q3T1J8, Q4R594, Q54IS6, Q5R9P9, Q5ZJN1, Q99K95, Q9BY42

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1655 predictions. Top by Δscore:

Variant	Effect	Δscore
20:56468649:G:GT	donor_gain	1.0000
20:56468763:GAAG:G	donor_gain	1.0000
20:56468765:AGGTC:A	donor_loss	1.0000
20:56473296:ATTAG:A	acceptor_gain	1.0000
20:56473297:T:G	acceptor_gain	1.0000
20:56473298:TAG:T	acceptor_loss	1.0000
20:56473299:A:AG	acceptor_gain	1.0000
20:56473299:AGGT:A	acceptor_loss	1.0000
20:56473300:G:GC	acceptor_gain	1.0000
20:56473300:GGTC:G	acceptor_gain	1.0000
20:56473393:CAGG:C	donor_loss	1.0000
20:56473394:AGGTA:A	donor_loss	1.0000
20:56473395:GGT:G	donor_loss	1.0000
20:56473396:G:GC	donor_loss	1.0000
20:56473397:T:G	donor_loss	1.0000
20:56474674:GCAG:G	acceptor_loss	1.0000
20:56474675:CAG:C	acceptor_loss	1.0000
20:56474676:A:AG	acceptor_gain	1.0000
20:56474676:AGACT:A	acceptor_loss	1.0000
20:56474677:G:GG	acceptor_gain	1.0000
20:56474677:G:GT	acceptor_loss	1.0000
20:56474677:GA:G	acceptor_gain	1.0000
20:56474677:GACT:G	acceptor_gain	1.0000
20:56474677:GACTT:G	acceptor_gain	1.0000
20:56476972:T:TA	acceptor_gain	1.0000
20:56476983:A:AG	acceptor_gain	1.0000
20:56476983:AGAAT:A	acceptor_gain	1.0000
20:56476984:G:A	acceptor_loss	1.0000
20:56476984:G:GG	acceptor_gain	1.0000
20:56476984:GA:G	acceptor_gain	1.0000

AlphaMissense

2019 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:56468738:T:C	L14P	1.000
20:56477087:T:C	C121R	1.000
20:56468701:G:C	G2R	0.999
20:56468707:G:C	D4H	0.999
20:56468708:A:T	D4V	0.999
20:56468711:G:A	G5E	0.999
20:56468714:G:A	G6E	0.999
20:56468720:T:A	I8N	0.999
20:56468720:T:C	I8T	0.999
20:56468723:C:A	P9H	0.999
20:56468729:G:C	R11T	0.999
20:56468729:G:T	R11M	0.999
20:56468730:G:C	R11S	0.999
20:56468730:G:T	R11S	0.999
20:56473377:T:A	V49D	0.999
20:56473392:G:A	G54D	0.999
20:56484112:T:C	F134L	0.999
20:56484114:C:A	F134L	0.999
20:56484114:C:G	F134L	0.999
20:56468702:G:A	G2D	0.998
20:56468708:A:C	D4A	0.998
20:56468708:A:G	D4G	0.998
20:56468709:C:A	D4E	0.998
20:56468709:C:G	D4E	0.998
20:56468710:G:A	G5R	0.998
20:56468710:G:C	G5R	0.998
20:56468710:G:T	G5W	0.998
20:56468711:G:T	G5V	0.998
20:56468713:G:A	G6R	0.998
20:56468713:G:C	G6R	0.998

dbSNP variants (sampled 300 via entrez): RS1000143480 (20:56492244 A>G), RS1000220069 (20:56489307 A>C,G), RS1000233454 (20:56480694 A>G), RS1000319060 (20:56512968 A>G), RS1000326944 (20:56491566 C>G), RS1000529142 (20:56519154 G>A,C), RS1000535007 (20:56481690 T>G), RS1000543340 (20:56471119 G>A), RS1000583032 (20:56508374 T>C), RS1000713654 (20:56487246 A>G), RS1000766975 (20:56513743 C>T), RS1000800917 (20:56508430 T>A), RS1000828762 (20:56498129 A>G), RS1000848436 (20:56508670 C>A,T), RS1000942819 (20:56497856 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

1 associations (top):

Study	Trait	p-value
GCST002579_14	Heschl’s gyrus morphology	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725112 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178973: Inhibition of C20ORF43 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression, decreases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Diuron	decreases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697703	Binding	Inhibition of C20ORF43 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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