PAF1

Summary

PAF1 (PAF1 component of Paf1/RNA polymerase II complex, HGNC:25459) is a protein-coding gene on chromosome 19q13.2, encoding RNA polymerase II-associated factor 1 homolog (Q8N7H5). 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 common-essential gene (DepMap: required in 93.3% of cancer cell lines).

This gene encodes a subunit of the polymerase associated factor (PAF1) complex. The PAF1 complex interacts with RNA polymerase II and plays a role in transcription elongation as well as histone modifications including ubiquitylation and methylation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 54623 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 60 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 93.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_019088

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25459
Approved symbol	PAF1
Name	PAF1 component of Paf1/RNA polymerase II complex
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	PD2, F23149_1, FLJ11123
Ensembl gene	ENSG00000006712
Ensembl biotype	protein_coding
OMIM	610506
Entrez	54623

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000221265, ENST00000416728, ENST00000595379, ENST00000595564, ENST00000595797, ENST00000597365, ENST00000598127, ENST00000598594, ENST00000859883, ENST00000859884, ENST00000859885, ENST00000859886, ENST00000934251, ENST00000964375

RefSeq mRNA: 2 — MANE Select: NM_019088 NM_001256826, NM_019088

CCDS: CCDS12533, CCDS59387

Canonical transcript exons

ENST00000221265 — 14 exons

Exon	Start	End
ENSE00000341661	39388339	39388467
ENSE00001141350	39388947	39389015
ENSE00001141380	39388560	39388676
ENSE00001141389	39388762	39388865
ENSE00001141406	39389282	39389383
ENSE00001141412	39389480	39389546
ENSE00001141419	39389640	39389761
ENSE00001141439	39385629	39386403
ENSE00003147051	39390818	39391106
ENSE00003485808	39386482	39386572
ENSE00003517756	39390069	39390161
ENSE00003579886	39386694	39386799
ENSE00003586918	39389093	39389198
ENSE00003601115	39390260	39390289

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.5818 / max 220.1252, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180859	31.8785	1821
180857	9.9593	1729
180860	5.2641	1732
180858	1.4776	868
180856	0.0023	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.98	gold quality
sural nerve	UBERON:0015488	98.15	gold quality
left testis	UBERON:0004533	95.92	gold quality
right testis	UBERON:0004534	95.66	gold quality
medial globus pallidus	UBERON:0002477	94.79	gold quality
mucosa of stomach	UBERON:0001199	94.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.58	gold quality
adenohypophysis	UBERON:0002196	94.43	gold quality
testis	UBERON:0000473	94.33	gold quality
ventricular zone	UBERON:0003053	94.21	gold quality
left ovary	UBERON:0002119	94.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.01	gold quality
right ovary	UBERON:0002118	93.96	gold quality
pituitary gland	UBERON:0000007	93.93	gold quality
ganglionic eminence	UBERON:0004023	93.90	gold quality
granulocyte	CL:0000094	93.84	gold quality
right adrenal gland	UBERON:0001233	93.71	gold quality
right adrenal gland cortex	UBERON:0035827	93.70	gold quality
left uterine tube	UBERON:0001303	93.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.60	gold quality
lower esophagus	UBERON:0013473	93.59	gold quality
left adrenal gland	UBERON:0001234	93.52	gold quality
left adrenal gland cortex	UBERON:0035825	93.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.45	gold quality
left lobe of thyroid gland	UBERON:0001120	93.44	gold quality
cerebellar hemisphere	UBERON:0002245	93.33	gold quality
stromal cell of endometrium	CL:0002255	93.30	gold quality
right lobe of thyroid gland	UBERON:0001119	93.30	gold quality
cerebellar cortex	UBERON:0002129	93.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KAT7, TP53

miRNA regulators (miRDB)

60 targeting PAF1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 39)

• Formation of trimeric complex UbcH6 and RNF20/40 with PAF stimulates histone 2B monoubiquitination activity in vitro (PMID:16307923)
• Overexpression of PD2/hPaf1 is involved in cancer development. (PMID:16491129)
• hPaf1 and the hPAF complex are key regulators of cell-cycle progression (PMID:19771162)
• Study demonstrates the ability of human PAF1C to facilitate activator p53- and histone acetyltransferase p300-dependent transcription elongation from a recombinant chromatin template in a biochemically defined RNA polymerase II transcription system. (PMID:20178742)
• MLL interacts directly with the polymerase associated factor complex (PAFc) via Paf1 and CTR9. PAFc augments MLL and MLL-AF9 mediated transcriptional activation of Hoxa9 and their interaction is essential for leukemogenesis. (PMID:20541477)
• Interaction between the Polymerase Associated Factor complex and Mixed Lineage Leukemia is critical for gene rearranged leukemogenesis. (PMID:21037944)
• that hPaf1/PD2 in association with MLL1 regulates methylation of H3K4 residues, as well as interacts and regulates nuclear shuttling of chromatin remodeling protein CHD1, facilitating its function in pancreatic cancer cells (PMID:22046413)
• PAF1c acts as an arginine methyl histone effector that is recruited to promoters and activates a subset of genes, including targets of estrogen signaling. (PMID:22451921)
• Data show that activation-induced deaminase (AID) associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain. (PMID:23008333)
• E1A changes the function of hBre1 from a ubiquitin ligase involved in substrate selection to a scaffold which recruits hPaf1 as a means to stimulate transcription and transcription-coupled histone modifications. (PMID:23785282)
• The results show that the Paf1/Leo1 heterodimer is necessary for its binding to histone H3, the histone octamer, and nucleosome in vitro. (PMID:24038468)
• 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)
• Together, these results indicate that human adenovirus E1A uses hBre1 to recruit the hPaf1 complex in order to optimally activate viral early transcription by enhancing transcriptional elongation. (PMID:24600005)
• PD2 is a novel cancer stem cell (CSC) maintenance protein, loss of which renders the CSCs more susceptible to drug-induced cell death. (PMID:25003666)
• CNOT4 controls the degradation of chromatin-unbound PAF1 via the 26S proteasome. (PMID:25933433)
• This study reveals an evolutionarily conserved role for PAF1 as a regulator of promoter-proximal pausing by RNA Pol II in all metazoans, including human. (PMID:26279188)
• Mechanistic studies indicated that PAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. (PMID:26282204)
• this study found that Pol II-associated factor 1 (PAF1) is a critical regulator of paused Pol II release, that positive transcription elongation factor b (P-TEFb) directly regulates the initial recruitment of PAF1 complex (PAF1C) to genes, and that the subsequent recruitment of CDK12 is dependent on PAF1C. (PMID:26659056)
• Propose that degradation of MYC limits the accumulation of MYC/PAF1C complexes during transcriptional activation. (PMID:26687678)
• Overexpression of PD2 leads to increased tumorigenicity and metastasis in pancreatic ductal adenocarcinoma. (PMID:26689992)
• High PAF1 expression is associated with ovarian cancer. (PMID:28122356)
• a subset of enhancers can primarily modulate gene expression by controlling the release of paused Pol II in a PAF1-dependent manner. (PMID:28860207)
• The various functions of Paf1C, such as the regulation of promoter-proximal pausing and development in higher eukaryotes, are complex and context dependent. (PMID:28870425)
• These results reveal ubiquitin-proteasome system regulation of Paf1 and suggest downregulation of ubiquitin-proteasome system in elevating Paf1’s abundance in poorly differentiated cancers. (PMID:29023102)
• Study reports 2.53 A atomic structures of both the human PAF1/CTR9 and yeast Paf1/Ctr9 heterodimers. Results clearly reveal that the heterodimer of PAF1/CTR9 or Paf1/Ctr9 is the core component of evolutionarily conserved multifunctional polymerase-associated factor 1 complex (Paf1C) and is important for human PAF1C or yeast Paf1C assembly, yeast viability, and Paf1C-mediated histone modifications. (PMID:30228257)
• These data highlight that human PAF1C is an important transcriptional regulator of expanded G4C2 within C9orf72 (PMID:31110321)
• Novel role of PAF1 in attenuating radiosensitivity in cervical cancer by inhibiting IER5 transcription. (PMID:32471508)
• RNA Polymerase II-Associated Factor 1 Regulates Stem Cell Features of Pancreatic Cancer Cells, Independently of the PAF1 Complex, via Interactions With PHF5A and DDX3. (PMID:32781084)
• A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair. (PMID:33637760)
• SUMO Modification of PAF1/PD2 Enables PML Interaction and Promotes Radiation Resistance in Pancreatic Ductal Adenocarcinoma. (PMID:34570619)
• Transcription recycling assays identify PAF1 as a driver for RNA Pol II recycling. (PMID:34732721)
• Crystal Structure of the Core Module of the Yeast Paf1 Complex. (PMID:34852272)
• Role of the Paf1 complex in the maintenance of stem cell pluripotency and development. (PMID:35869661)
• PAF1 cooperates with YAP1 in metaplastic ducts to promote pancreatic cancer. (PMID:36180487)
• Elevated PAF1-RAD52 axis confers chemoresistance to human cancers. (PMID:36709426)
• CNOT4 suppresses nonsmall cell lung cancer progression by promoting the degradation of PAF1. (PMID:37493105)
• Aberrant accumulation of Kras-dependent pervasive transcripts during tumor progression renders cancer cells dependent on PAF1 expression. (PMID:37572321)
• RFX2 promotes tumor cell stemness through epigenetic regulation of PAF1 in spinal ependymoma. (PMID:38057505)
• NELF and PAF1C complexes are core transcriptional machineries controlling colon cancer stemness. (PMID:38182897)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	paf1	ENSDARG00000098432
mus_musculus	Paf1	ENSMUSG00000003437
rattus_norvegicus	Paf1	ENSRNOG00000019746
drosophila_melanogaster	atms	FBGN0010750
drosophila_melanogaster	CG12674	FBGN0031388
caenorhabditis_elegans		WBGENE00008338
caenorhabditis_elegans		WBGENE00018374

Protein

Protein identifiers

RNA polymerase II-associated factor 1 homolog — Q8N7H5 (reviewed: Q8N7H5)

Alternative names: Pancreatic differentiation protein 2

All UniProt accessions (3): Q8N7H5, B4DGJ5, M0QYC7

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. Connects PAF1C with the RNF20/40 E3 ubiquitin-protein ligase complex. Involved in polyadenylation of mRNA precursors. Has oncogenic activity in vivo and in vitro.

Subunit / interactions. Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8. The PAF1 complex interacts with PHF5A. Interacts with POLR2A, TCEA1, SKIC3, KMT2A/MLL1, SUPT5H, RNF20 and RNF40. Interacts with UBE2E1. Interacts with PINT87aa which is encoded by the circular form of the long non-coding RNA LINC-PINT; the interaction enhances the binding of the PAF1 complex to target gene promoters and may anchor the complex on target gene promoters, sequentially pausing RNA polymerase II-induced mRNA elongation. (Microbial infection) Interacts with influenza A strain H3N2 NS1 protein; the interaction interferes with host cell gene transcription, specifically with that of antiviral genes. (Microbial infection) The PAF1 complex interacts with Zika virus French Polynesia 10087PF/2013 non-structural protein 5/NS5. The interaction with viral NS5 proteins may reduce the antiviral immune response by inhibiting the recruitment of the PAF1 complex to interferon-stimulated genes, thus preventing their transcription. (Microbial infection) The PAF1 complex interacts with Dengue virus DENV2 16681 non-structural protein 5/NS5. The PAF1 complex interacts with Dengue virus DENV4 Dominica/814669/1981 non-structural protein 5/NS5. The interaction with viral NS5 proteins may reduce the antiviral immune response by inhibiting the recruitment of the PAF1 complex to interferon-stimulated genes, thus preventing their transcription.

Subcellular location. Nucleus.

Similarity. Belongs to the PAF1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N7H5-1	1	yes
Q8N7H5-2	2
Q8N7H5-3	3

RefSeq proteins (2): NP_001243755, NP_061961* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007133	RNA_pol_II-assoc_Paf1	Family

Pfam: PF03985

UniProt features (49 total): strand 14, compositionally biased region 7, helix 6, splice variant 5, sequence conflict 4, turn 4, region of interest 3, modified residue 2, cross-link 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
9HVQ	ELECTRON MICROSCOPY	2
9MLC	ELECTRON MICROSCOPY	2.4
4M6T	X-RAY DIFFRACTION	2.5
5ZYQ	X-RAY DIFFRACTION	2.53
7OOP	ELECTRON MICROSCOPY	2.9
9EGX	ELECTRON MICROSCOPY	2.9
9EGY	ELECTRON MICROSCOPY	2.9
9EGZ	ELECTRON MICROSCOPY	2.9
7OPC	ELECTRON MICROSCOPY	3
7OPD	ELECTRON MICROSCOPY	3
7UNC	ELECTRON MICROSCOPY	3
7UND	ELECTRON MICROSCOPY	3
6GMH	ELECTRON MICROSCOPY	3.1
6TED	ELECTRON MICROSCOPY	3.1
9EH2	ELECTRON MICROSCOPY	3.1
8A3Y	ELECTRON MICROSCOPY	3.3
9EH0	ELECTRON MICROSCOPY	3.6
9RTT	ELECTRON MICROSCOPY	4.01
9S3G	ELECTRON MICROSCOPY	6.4
9S0U	ELECTRON MICROSCOPY	6.72
9RZE	ELECTRON MICROSCOPY	8.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N7H5-F1	67.91	0.11

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 (4): 117, 456, 133, 154

Function

Pathways and Gene Ontology

Reactome pathways

6 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

MSigDB gene sets: 202 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, JI_RESPONSE_TO_FSH_UP, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_CELL_FATE_COMMITMENT_INVOLVED_IN_FORMATION_OF_PRIMARY_GERM_LAYER, KOYAMA_SEMA3B_TARGETS_UP, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_MRNA_3_END_PROCESSING, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), endodermal cell fate commitment (GO:0001711), transcription elongation by RNA polymerase II (GO:0006368), Wnt signaling pathway (GO:0016055), stem cell population maintenance (GO:0019827), mRNA 3’-end processing (GO:0031124), protein localization to nucleus (GO:0034504), negative regulation of myeloid cell differentiation (GO:0045638), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to lipopolysaccharide (GO:0071222), positive regulation of cell cycle G1/S phase transition (GO:1902808)

GO Molecular Function (3): RNA polymerase II complex binding (GO:0000993), chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), membrane (GO:0016020), Cdc73/Paf1 complex (GO:0016593), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-5 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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transcription by RNA polymerase II	3
regulation of transcription by RNA polymerase II	2
binding	2
negative regulation of DNA-templated transcription	1
endodermal cell differentiation	1
cell fate commitment involved in formation of primary germ layer	1
DNA-templated transcription elongation	1
cell surface receptor signaling pathway	1
multicellular organismal process	1
maintenance of cell number	1
mRNA processing	1
RNA 3’-end processing	1
protein localization to organelle	1
myeloid cell differentiation	1
negative regulation of cell differentiation	1
regulation of myeloid cell differentiation	1
positive regulation of DNA-templated transcription	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
cell cycle G1/S phase transition	1
positive regulation of cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
RNA polymerase core enzyme binding	1
nucleolus	1
nuclear lumen	1
intracellular anatomical structure	1
transcription elongation factor complex	1
RNA polymerase II, holoenzyme	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1521 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAF1	RNF20	Q5VTR2	900
PAF1	CDC73	Q6P1J9	833
PAF1	CTR9	Q6PD62	798
PAF1	RNF40	O75150	790
PAF1	LEO1	Q8WVC0	787
PAF1	RTF1	Q92541	578
PAF1	TECR	Q9NZ01	571
PAF1	NOL4	O94818	571
PAF1	SNCA	P37840	533
PAF1	NDUFAF3	Q9BU61	515
PAF1	RCC1	P18754	494
PAF1	SKIC8	Q9GZS3	491
PAF1	SERF1A	O75920	447
PAF1	PUSL1	Q8N0Z8	446
PAF1	POLI	Q9UNA4	443

IntAct

215 interactions, top by confidence:

A	B	Type	Score
CCNT1	CDK9	psi-mi:“MI:0914”(association)	0.980
PAF1	CDC73	psi-mi:“MI:0914”(association)	0.960
CDC73	PAF1	psi-mi:“MI:0915”(physical association)	0.960
PAF1	CDC73	psi-mi:“MI:0915”(physical association)	0.960
PAF1	LEO1	psi-mi:“MI:0915”(physical association)	0.950
LEO1	PAF1	psi-mi:“MI:0915”(physical association)	0.950
CDC73	CTR9	psi-mi:“MI:0914”(association)	0.940
CTR9	CDC73	psi-mi:“MI:0914”(association)	0.940
CDC73	CTR9	psi-mi:“MI:0915”(physical association)	0.940

BioGRID (370): PAF1 (Two-hybrid), LEO1 (Two-hybrid), CDK9 (Co-fractionation), PAF1 (Co-fractionation), PAF1 (Reconstituted Complex), PAF1 (Reconstituted Complex), PAF1 (Affinity Capture-MS), PAF1 (Affinity Capture-MS), PAF1 (Affinity Capture-Western), PAF1 (Affinity Capture-MS), PAF1 (Two-hybrid), PAF1 (Affinity Capture-Western), CDC7 (Co-fractionation), CDC73 (Co-fractionation), CHD1 (Co-fractionation)

ESM2 similar proteins: A2BD83, F4HQA1, F4HRV8, F4ICK8, O43290, P21675, P35269, Q04870, Q13435, Q15545, Q1RMR0, Q2HJG8, Q2KJ14, Q3THK3, Q3UJB0, Q4R5A5, Q4U0S5, Q4V886, Q52KV5, Q53F19, Q5EA53, Q5HZB6, Q5R4D6, Q5R7L9, Q5RAX0, Q5XIW8, Q5XJE5, Q5ZHP7, Q5ZIH9, Q5ZIM6, Q5ZM19, Q641X2, Q6AY96, Q6NYV9, Q6P2Y1, Q6R1L1, Q80UV9, Q811X5, Q8BZR9, Q8CFC7

Diamond homologs: A2BD83, P90783, Q2KJ14, Q4U0S5, Q4V886, Q5RAX0, Q6P2Y1, Q8K2T8, Q8N7H5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PAF1	“form complex”	PAF1C	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 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
HIV elongation arrest and recovery	12	42.0×	3e-15
Pausing and recovery of HIV elongation	12	42.0×	3e-15
Pausing and recovery of Tat-mediated HIV elongation	11	40.9×	7e-14
Tat-mediated HIV elongation arrest and recovery	11	40.9×	7e-14
FGFR2 mutant receptor activation	5	38.5×	1e-06
Signaling by FGFR2 IIIa TM	6	36.4×	1e-07
Abortive elongation of HIV-1 transcript in the absence of Tat	7	35.1×	1e-08
HIV Transcription Elongation	10	33.9×	7e-12

GO biological processes:

GO term	Partners	Fold	FDR
transcription elongation by RNA polymerase II	9	34.7×	2e-09
positive regulation of transcription elongation by RNA polymerase II	9	23.6×	5e-08
stem cell population maintenance	6	22.0×	5e-05
Wnt signaling pathway	9	7.8×	2e-04
transcription by RNA polymerase II	11	6.7×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	2
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1431 predictions. Top by Δscore:

Variant	Effect	Δscore
19:39386477:TTTAC:T	donor_loss	1.0000
19:39386478:TTACC:T	donor_loss	1.0000
19:39386479:TACC:T	donor_loss	1.0000
19:39386480:A:T	donor_loss	1.0000
19:39386481:CCT:C	donor_loss	1.0000
19:39386496:T:TA	donor_gain	1.0000
19:39386568:GCCTC:G	acceptor_gain	1.0000
19:39386569:CCTCC:C	acceptor_gain	1.0000
19:39386570:CTC:C	acceptor_gain	1.0000
19:39386571:TC:T	acceptor_gain	1.0000
19:39386572:CC:C	acceptor_gain	1.0000
19:39386573:C:CC	acceptor_gain	1.0000
19:39386580:C:CT	acceptor_gain	1.0000
19:39386581:A:T	acceptor_gain	1.0000
19:39386583:C:CT	acceptor_gain	1.0000
19:39386584:A:T	acceptor_gain	1.0000
19:39386588:T:TC	acceptor_gain	1.0000
19:39386688:TGTTA:T	donor_loss	1.0000
19:39386689:GTTAC:G	donor_loss	1.0000
19:39386690:TTA:T	donor_loss	1.0000
19:39386691:TACCT:T	donor_loss	1.0000
19:39386795:GGACC:G	acceptor_gain	1.0000
19:39386796:GACC:G	acceptor_gain	1.0000
19:39386797:ACC:A	acceptor_gain	1.0000
19:39386798:CC:C	acceptor_gain	1.0000
19:39386798:CCC:C	acceptor_gain	1.0000
19:39386799:CC:C	acceptor_gain	1.0000
19:39386800:C:CA	acceptor_loss	1.0000
19:39386800:C:CC	acceptor_gain	1.0000
19:39386800:C:T	acceptor_gain	1.0000

AlphaMissense

3595 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:39386225:A:C	F454L	1.000
19:39386225:A:T	F454L	1.000
19:39386227:A:G	F454L	1.000
19:39386553:A:G	L371P	1.000
19:39386553:A:T	L371Q	1.000
19:39386560:C:G	A369P	1.000
19:39386565:C:G	R367P	1.000
19:39386565:C:T	R367Q	1.000
19:39386566:G:C	R367G	1.000
19:39386569:C:G	A366P	1.000
19:39386695:T:G	Q364P	1.000
19:39386699:C:G	A363P	1.000
19:39386708:C:T	E360K	1.000
19:39386725:C:G	R354P	1.000
19:39386729:G:C	H353D	1.000
19:39386734:A:T	V351D	1.000
19:39386740:A:C	L349R	1.000
19:39386740:A:G	L349P	1.000
19:39386740:A:T	L349H	1.000
19:39386782:C:G	R335P	1.000
19:39386783:G:T	R335S	1.000
19:39386784:C:A	K334N	1.000
19:39386784:C:G	K334N	1.000
19:39386785:T:A	K334M	1.000
19:39386786:T:C	K334E	1.000
19:39386787:A:C	S333R	1.000
19:39386787:A:T	S333R	1.000
19:39386789:T:G	S333R	1.000
19:39386791:A:C	L332R	1.000
19:39386791:A:G	L332P	1.000

dbSNP variants (sampled 300 via entrez): RS1000004715 (19:39387518 C>T), RS1000536828 (19:39387971 CTA>C), RS1001215456 (19:39392816 A>G), RS1001838590 (19:39391398 A>C,G,T), RS1001938821 (19:39388700 A>C), RS1002312358 (19:39391704 A>G,T), RS1002367293 (19:39385380 G>A), RS1003016887 (19:39390050 T>C), RS1003573394 (19:39393044 C>T), RS1003950804 (19:39392835 A>G), RS1004305827 (19:39391603 A>G), RS1004492144 (19:39390892 G>A), RS1004633261 (19:39393013 G>C,T), RS1005494447 (19:39391674 T>A,C), RS1005538507 (19:39392566 G>A)

Disease associations

OMIM: gene MIM:610506 | disease phenotypes: MIM:214100

GenCC curated gene-disease

Mondo (1): peroxisome biogenesis disorder 1A (Zellweger) (MONDO:0008953)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725179 (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

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.19	Kd	65	nM	MOLIBRESIB
7.11	Kd	78	nM	MOLIBRESIB
7.10	IC50	80	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 8 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	2174626: Binding affinity to PAF1 (unknown origin) assessed as apparent dissociation constant	kd	0.0650	uM

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, affects expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Smoke	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
bromovanin	decreases expression	1
Vehicle Emissions	decreases expression, decreases reaction	1
Diazinon	increases methylation	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Ozone	affects expression, increases abundance	1
Potassium Dichromate	increases expression	1
Ribonucleotides	affects binding	1
Dronabinol	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, decreases reaction	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5696856	Binding	Binding affinity to PAF1 (unknown origin) assessed as apparent dissociation constant	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.