RTF1

Summary

RTF1 (RTF1 homolog, Paf1/RNA polymerase II complex component, HGNC:28996) is a protein-coding gene on chromosome 15q15.1, encoding RNA polymerase-associated protein RTF1 homolog (Q92541). Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. It is a selective cancer dependency (DepMap: 80.1% of cell lines).

This locus may represent a gene involved in regulation of transcription elongation and chromatin remodeling, based on studies of similar proteins in other organisms. The encoded protein may bind single-stranded DNA.

Source: NCBI Gene 23168 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 54 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 80.1% of screened cell lines
• MANE Select transcript: NM_015138

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28996
Approved symbol	RTF1
Name	RTF1 homolog, Paf1/RNA polymerase II complex component
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137815
Ensembl biotype	protein_coding
OMIM	611633
Entrez	23168

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000389629, ENST00000462276, ENST00000473214, ENST00000558117, ENST00000558298, ENST00000560447, ENST00000561076, ENST00000925186, ENST00000925187

RefSeq mRNA: 1 — MANE Select: NM_015138 NM_015138

CCDS: CCDS32200

Canonical transcript exons

ENST00000389629 — 18 exons

Exon	Start	End
ENSE00000931009	41457672	41457876
ENSE00000931011	41466141	41466252
ENSE00000931012	41470257	41470392
ENSE00000931013	41471172	41471349
ENSE00000931014	41474620	41474702
ENSE00000931020	41478548	41478625
ENSE00000931022	41480214	41480325
ENSE00001029847	41464771	41464885
ENSE00001152986	41477165	41477286
ENSE00001644351	41452901	41453048
ENSE00001944328	41480581	41483563
ENSE00002238070	41417095	41417313
ENSE00003463812	41475712	41475819
ENSE00003526957	41438321	41438431
ENSE00003558702	41477458	41477515
ENSE00003617339	41475525	41475612
ENSE00003661749	41479103	41479198
ENSE00003670789	41476446	41476523

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 96.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.9926 / max 1865.9699, expressed in 1821 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146182	53.2788	1820
146183	4.7139	1456

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.57	gold quality
ganglionic eminence	UBERON:0004023	95.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.36	gold quality
embryo	UBERON:0000922	94.15	gold quality
palpebral conjunctiva	UBERON:0001812	93.39	gold quality
colonic epithelium	UBERON:0000397	93.27	gold quality
ventricular zone	UBERON:0003053	92.83	gold quality
bone marrow cell	CL:0002092	92.78	gold quality
biceps brachii	UBERON:0001507	92.62	gold quality
cerebellar hemisphere	UBERON:0002245	92.62	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.62	gold quality
cerebellar cortex	UBERON:0002129	92.59	gold quality
adrenal tissue	UBERON:0018303	92.58	gold quality
body of tongue	UBERON:0011876	92.56	gold quality
monocyte	CL:0000576	92.48	gold quality
mononuclear cell	CL:0000842	92.43	gold quality
cauda epididymis	UBERON:0004360	92.35	gold quality
caput epididymis	UBERON:0004358	92.24	gold quality
saphenous vein	UBERON:0007318	92.20	gold quality
penis	UBERON:0000989	92.14	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.14	gold quality
leukocyte	CL:0000738	92.09	gold quality
urinary bladder	UBERON:0001255	92.05	gold quality
cerebellum	UBERON:0002037	92.02	gold quality
calcaneal tendon	UBERON:0003701	91.96	gold quality
upper leg skin	UBERON:0004262	91.93	gold quality
seminal vesicle	UBERON:0000998	91.90	gold quality
urethra	UBERON:0000057	91.87	gold quality
tonsil	UBERON:0002372	91.83	gold quality
blood vessel layer	UBERON:0004797	91.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.68
E-GEOD-70580	no	240.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

174 targeting RTF1, 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-8485	100.00	77.57	4731
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6825-5P	99.96	69.81	3431

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 80.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• Data indicate that the Plus3 domain of the Rtf1 subunit mediates Paf1C recruitment to genes by binding a repeating domain within the phosphorylated elongation factor Spt5. (PMID:24101474)
• Human Rtf1 as a transcription elongation factor. (PMID:26217014)
• Structure of complete Pol II-DSIF-PAF-SPT6 transcription complex reveals RTF1 allosteric activation. (PMID:32541898)
• Two distinct mechanisms of RNA polymerase II elongation stimulation in vivo. (PMID:34146481)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rtf1	ENSDARG00000008947
mus_musculus	Rtf1	ENSMUSG00000027304
rattus_norvegicus	Rtf1	ENSRNOG00000005183
drosophila_melanogaster	CG12498	FBGN0040356
drosophila_melanogaster	tplus3a	FBGN0051702
drosophila_melanogaster	tplus3b	FBGN0051703

Protein

Protein identifiers

RNA polymerase-associated protein RTF1 homolog — Q92541 (reviewed: Q92541)

All UniProt accessions (2): Q92541, H0YKX1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and ‘Ser-2’- and ‘Ser-5’-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 ‘Lys-4’ (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of ‘Lys-120’ of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3’ end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Binds single-stranded DNA. Required for maximal induction of heat-shock genes. Required for the trimethylation of histone H3 ‘Lys-4’ (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of a SET1 complex.

Subunit / interactions. Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8; the association of RTF1 appears to be less stable than that of other subunits. At least in HeLa cells a N-terminal shorter form of RTF1 is also found in the complex. The PAF1 complex interacts with PHF5A.

Subcellular location. Nucleus. Nucleoplasm.

Domain organisation. The Plus3 domain mediates single-stranded DNA-binding.

RefSeq proteins (1): NP_055953* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004343	Plus-3_dom	Domain
IPR036128	Plus3-like_sf	Homologous_superfamily

Pfam: PF03126

UniProt features (48 total): compositionally biased region 11, helix 10, strand 8, modified residue 6, mutagenesis site 5, region of interest 4, chain 1, domain 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
3U1U	X-RAY DIFFRACTION	1.8
4L1P	X-RAY DIFFRACTION	2.12
4L1U	X-RAY DIFFRACTION	2.42
9EGX	ELECTRON MICROSCOPY	2.9
9EGY	ELECTRON MICROSCOPY	2.9
9EGZ	ELECTRON MICROSCOPY	2.9
7UNC	ELECTRON MICROSCOPY	3
7UND	ELECTRON MICROSCOPY	3
6TED	ELECTRON MICROSCOPY	3.1
9EH1	ELECTRON MICROSCOPY	3.1
9EH2	ELECTRON MICROSCOPY	3.1
8A3Y	ELECTRON MICROSCOPY	3.3
9EH0	ELECTRON MICROSCOPY	3.6
9S3G	ELECTRON MICROSCOPY	6.4
9S0U	ELECTRON MICROSCOPY	6.72
9RZE	ELECTRON MICROSCOPY	8.53
2BZE	SOLUTION NMR
2DB9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92541-F1	68.15	0.19

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 (6): 53, 55, 626, 650, 655, 697

Mutagenesis-validated functional residues (5):

Position	Phenotype
401	loss of binding to single-stranded dna.
410	reduced binding to single-stranded dna.
429	loss of binding to single-stranded dna.
434	reduced binding to single-stranded dna.
435	loss of binding to single-stranded dna.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses
R-HSA-9943411	CHD1 and CHD2 subfamily
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8852135	Protein ubiquitination

MSigDB gene sets: 196 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, WANG_CLIM2_TARGETS_UP, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GGGNRMNNYCAT_UNKNOWN, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, SP3_Q3, GOBP_GROWTH, ATGCAGT_MIR217, SP1_Q2_01, E2F_Q3, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GATA3_01, GOBP_CELL_FATE_COMMITMENT_INVOLVED_IN_FORMATION_OF_PRIMARY_GERM_LAYER, ZHAN_V2_LATE_DIFFERENTIATION_GENES, GTGTTGA_MIR505

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), endodermal cell fate commitment (GO:0001711), blastocyst growth (GO:0001832), chromatin organization (GO:0006325), transcription elongation by RNA polymerase II (GO:0006368), Wnt signaling pathway (GO:0016055), stem cell population maintenance (GO:0019827)

GO Molecular Function (4): single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), nucleolus (GO:0005730), Cdc73/Paf1 complex (GO:0016593), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
RNA Polymerase II Transcription	2
RNA Polymerase II Transcription Elongation	1
Protein ubiquitination	1
Dengue Virus-Host Interactions	1
CHD chromatin remodelers	1
Metabolism of proteins	1
Gene expression (Transcription)	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
nucleic acid binding	2
nuclear lumen	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
endodermal cell differentiation	1
cell fate commitment involved in formation of primary germ layer	1
blastocyst development	1
developmental growth	1
cellular component organization	1
DNA-templated transcription elongation	1
cell surface receptor signaling pathway	1
multicellular organismal process	1
maintenance of cell number	1
DNA binding	1
binding	1
cellular anatomical structure	1
intracellular membraneless organelle	1
transcription elongation factor complex	1
RNA polymerase II, holoenzyme	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RTF1	LEO1	Q8WVC0	999
RTF1	CTR9	Q6PD62	998
RTF1	CDC73	Q6P1J9	997
RTF1	SKIC8	Q9GZS3	997
RTF1	CHD1	O14646	922
RTF1	SUPT5H	O00267	894
RTF1	RNF20	Q5VTR2	840
RTF1	SETD1A	O15047	775
RTF1	RPAP2	Q8IXW5	746
RTF1	RTF2	Q9BY42	739
RTF1	SUPT6H	Q7KZ85	715
RTF1	SUPT4H1	P63272	710
RTF1	SUPT16H	Q9Y5B9	688
RTF1	TCEA2	Q15560	614
RTF1	TCEA1	P23193	614

IntAct

92 interactions, top by confidence:

A	B	Type	Score
PAF1	CDC73	psi-mi:“MI:0914”(association)	0.960
CDC73	CTR9	psi-mi:“MI:0915”(physical association)	0.940
CTR9	CDC73	psi-mi:“MI:0914”(association)	0.940
CDC73	LEO1	psi-mi:“MI:0403”(colocalization)	0.930
PAF1	CTR9	psi-mi:“MI:0914”(association)	0.910
CTR9	PAF1	psi-mi:“MI:0914”(association)	0.910
PAF1	RTF1	psi-mi:“MI:0915”(physical association)	0.770
RTF1	PAF1	psi-mi:“MI:0915”(physical association)	0.770
RTF1	CDC73	psi-mi:“MI:0914”(association)	0.750
RTF1	CDC73	psi-mi:“MI:0915”(physical association)	0.750
PAF1	POLR2A	psi-mi:“MI:0914”(association)	0.710
POLR2A	CDC73	psi-mi:“MI:0914”(association)	0.710

BioGRID (199): RTF1 (Affinity Capture-MS), CHD1 (Co-fractionation), CTR9 (Co-fractionation), RPL37 (Co-fractionation), RTF1 (Co-fractionation), RTF1 (Co-fractionation), RTF1 (Co-fractionation), RTF1 (Co-fractionation), RTF1 (Co-fractionation), RTF1 (Co-fractionation), RTF1 (Co-fractionation), RTF1 (Co-fractionation), SRRM2 (Co-fractionation), SUPT16H (Co-fractionation), SUPT5H (Co-fractionation)

ESM2 similar proteins: A0JNI5, A2AJT4, A2AQ19, A4IFB1, B1H1X4, D3ZTQ1, O43290, P35269, Q05519, Q12872, Q13435, Q3THK3, Q3UJB0, Q3UQU0, Q3USH5, Q4V7C9, Q53F19, Q568R1, Q5EA53, Q5HZB6, Q5PQQ2, Q5R539, Q5RAD5, Q5XIW8, Q5ZM19, Q66I22, Q6AY96, Q6DDA4, Q6GLZ8, Q6INH5, Q6ZPZ3, Q8BZR9, Q8CFC7, Q8K194, Q8N2M8, Q8N5F7, Q8TF01, Q8VHI6, Q8WVK2, Q923D5

Diamond homologs: A2AQ19, G5EBY0, O94667, Q5RAD5, Q92541, Q9W261, Q9C950, Q9SIV5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RTF1	“form complex”	PAF1C	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
Formation of RNA Pol II elongation complex	7	24.2×	2e-06
RNA Polymerase II Transcription Elongation	7	24.2×	2e-06
E3 ubiquitin ligases ubiquitinate target proteins	7	24.2×	2e-06
RNA Polymerase II Pre-transcription Events	7	17.2×	1e-05
CHD1 and CHD2 subfamily	7	13.6×	4e-05
Processing of Capped Intron-Containing Pre-mRNA	7	10.3×	2e-04
mRNA Splicing	5	9.8×	4e-03
mRNA Splicing - Major Pathway	10	9.8×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
transcription elongation by RNA polymerase II	7	46.3×	7e-08
stem cell population maintenance	5	31.4×	9e-05
Wnt signaling pathway	7	10.4×	5e-04
RNA splicing	6	7.9×	6e-03

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	36
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2557 predictions. Top by Δscore:

Variant	Effect	Δscore
15:41417311:CAGG:C	donor_loss	1.0000
15:41417312:AGG:A	donor_loss	1.0000
15:41417313:GGTGA:G	donor_loss	1.0000
15:41417314:G:GC	donor_loss	1.0000
15:41417315:T:G	donor_loss	1.0000
15:41438316:ATTAG:A	acceptor_gain	1.0000
15:41438317:TTA:T	acceptor_loss	1.0000
15:41438317:TTAGG:T	acceptor_gain	1.0000
15:41438318:TAG:T	acceptor_loss	1.0000
15:41438318:TAGG:T	acceptor_gain	1.0000
15:41438319:A:AG	acceptor_gain	1.0000
15:41438319:AG:A	acceptor_gain	1.0000
15:41438319:AGGA:A	acceptor_gain	1.0000
15:41438320:G:C	acceptor_loss	1.0000
15:41438320:G:GT	acceptor_gain	1.0000
15:41438320:GG:G	acceptor_gain	1.0000
15:41438320:GGA:G	acceptor_gain	1.0000
15:41438320:GGAG:G	acceptor_gain	1.0000
15:41438320:GGAGC:G	acceptor_gain	1.0000
15:41438429:GAG:G	donor_gain	1.0000
15:41438430:AGG:A	donor_loss	1.0000
15:41438432:G:GG	donor_gain	1.0000
15:41438432:GT:G	donor_loss	1.0000
15:41452897:ATAGT:A	acceptor_gain	1.0000
15:41452899:A:AG	acceptor_gain	1.0000
15:41452899:AGT:A	acceptor_gain	1.0000
15:41452900:G:GA	acceptor_gain	1.0000
15:41452900:GT:G	acceptor_gain	1.0000
15:41452900:GTG:G	acceptor_gain	1.0000
15:41457667:TGCAG:T	acceptor_loss	1.0000

AlphaMissense

4682 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:41457801:T:C	L196P	1.000
15:41457825:G:C	R204T	1.000
15:41457826:A:C	R204S	1.000
15:41457826:A:T	R204S	1.000
15:41457831:A:C	Q206P	1.000
15:41457837:T:C	L208P	1.000
15:41457845:C:A	R211S	1.000
15:41457845:C:G	R211G	1.000
15:41457846:G:C	R211P	1.000
15:41464791:T:C	L228P	1.000
15:41466217:T:C	L285P	1.000
15:41471204:T:A	V353D	1.000
15:41471222:T:C	L359S	1.000
15:41471234:G:C	R363P	1.000
15:41471242:C:G	R366G	1.000
15:41471243:G:C	R366P	1.000
15:41471252:T:C	L369P	1.000
15:41471260:T:A	W372R	1.000
15:41471260:T:C	W372R	1.000
15:41471291:T:A	V382D	1.000
15:41471306:T:A	V387E	1.000
15:41471309:G:C	R388P	1.000
15:41471312:T:A	I389N	1.000
15:41471315:G:A	G390D	1.000
15:41471318:T:A	I391N	1.000
15:41471320:G:A	G392R	1.000
15:41471320:G:C	G392R	1.000
15:41471321:G:A	G392E	1.000
15:41471321:G:T	G392V	1.000
15:41471342:T:A	V399D	1.000

dbSNP variants (sampled 300 via entrez): RS1000117666 (15:41479307 G>C,T), RS1000118948 (15:41458789 A>T), RS1000134767 (15:41417815 T>C), RS1000148385 (15:41452449 C>G,T), RS1000198900 (15:41424004 T>C), RS1000215301 (15:41470088 T>G), RS1000229175 (15:41468900 T>C), RS1000298132 (15:41435460 C>A), RS1000348659 (15:41435235 A>G), RS1000383963 (15:41435455 G>A), RS1000395920 (15:41429940 AAGGACC>A), RS1000428855 (15:41481415 A>G), RS1000562747 (15:41431545 C>G), RS1000573207 (15:41470037 T>A), RS1000612826 (15:41437207 T>C)

Disease associations

OMIM: gene MIM:611633 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000817_157	Height	1.000000e-12
GCST004133_26	Ulcerative colitis	3.000000e-07
GCST004617_155	Eosinophil percentage of granulocytes	1.000000e-12
GCST004861_17	Itch intensity from mosquito bite	5.000000e-07
GCST005038_89	Allergic disease (asthma, hay fever or eczema)	5.000000e-10
GCST005196_7	Coronary artery disease	2.000000e-07
GCST006409_2	Allergic rhinitis	1.000000e-14
GCST007563_20	Allergic disease (asthma, hay fever or eczema)	4.000000e-08
GCST010043_21	Asthma	1.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007996	eosinophil percentage of granulocytes
EFO:0008377	mosquito bite reaction itch intensity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725131 (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

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.68	Kd	21	nM	MOLIBRESIB
7.52	IC50	30	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 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	2179161: Binding affinity against RTF1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0210	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, decreases expression	2
Acetaminophen	increases expression	2
FR900359	decreases phosphorylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Benzo(a)pyrene	affects methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Methapyrilene	increases methylation	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	affects methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697232	Binding	Inhibition of RTF1 (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.