PAF1

PAF1 homolog, Paf1/RNA polymerase II complex component, the group of Paf1/RNA polymerase II complex

Basic information

Region (hg38): 19:39385629-39391154

Links

ENSG00000006712 ∙ NCBI:54623 ∙ OMIM:610506 ∙ HGNC:25459 ∙ Uniprot:Q8N7H5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAF1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAF1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			23			23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					5	5
Total	0	0	23	1	6

Variants in PAF1

This is a list of pathogenic ClinVar variants found in the PAF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-39386047-C-T		not specified	Uncertain significance (Mar 14, 2025)
19-39386088-G-C		not specified	Uncertain significance (Jan 25, 2023)
19-39386110-T-C		not specified	Uncertain significance (Jun 28, 2024)
19-39386122-C-T		not specified	Uncertain significance (Aug 14, 2023)
19-39386127-T-C		not specified	Uncertain significance (Mar 03, 2025)
19-39386142-G-A		Peroxisome biogenesis disorder 1A (Zellweger)	Uncertain significance (Mar 29, 2024)
19-39386155-T-C		not specified	Uncertain significance (Jan 18, 2023)
19-39386164-G-C		not specified	Uncertain significance (Feb 06, 2023)
19-39386168-C-G		not specified	Uncertain significance (Apr 17, 2024)
19-39386175-C-T		not specified	Uncertain significance (Feb 20, 2025)
19-39386185-C-G		not specified	Uncertain significance (Jan 20, 2023)
19-39386271-C-T		not specified	Uncertain significance (Jan 26, 2022)
19-39386346-G-A		not specified	Uncertain significance (Oct 18, 2021)
19-39386495-T-G		not specified	Uncertain significance (Jun 09, 2022)
19-39386497-C-T		not specified	Uncertain significance (Nov 28, 2023)
19-39386965-T-C			Benign (Jun 21, 2021)
19-39387096-T-C			Benign (Jun 19, 2021)
19-39388317-C-G			Benign (Jun 20, 2021)
19-39388372-C-T		not specified	Uncertain significance (Jun 11, 2024)
19-39388412-T-C		not specified	Uncertain significance (Jan 09, 2025)
19-39388414-C-G		not specified	Uncertain significance (Apr 27, 2024)
19-39388456-T-C		not specified	Uncertain significance (Jan 09, 2024)
19-39388504-C-T			Benign (Jun 21, 2021)
19-39388572-G-A		not specified	Uncertain significance (May 24, 2023)
19-39388601-C-A		not specified	Uncertain significance (Jan 18, 2025)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAF1	protein_coding	protein_coding	ENST00000221265	14	5344

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000169	1.00	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.75	173	309	0.559	0.0000191	3582
Missense in Polyphen		28	98.385	0.2846		1134
Synonymous	-0.0801	113	112	1.01	0.00000720	911
Loss of Function	3.19	12	31.2	0.384	0.00000180	351

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000617	0.0000615
Middle Eastern	0.000326	0.000326
South Asian	0.000137	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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 indepentently 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. {ECO:0000269|PubMed:16491129, ECO:0000269|PubMed:19410543, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879, ECO:0000269|PubMed:22419161}.
• Pathway: Endoderm Differentiation;Gene expression (Transcription);RNA Polymerase II Pre-transcription Events;Post-translational protein modification;Formation of RNA Pol II elongation complex ;Metabolism of proteins;RNA Polymerase II Transcription;RNA Polymerase II Transcription Elongation;Protein ubiquitination;E3 ubiquitin ligases ubiquitinate target proteins (Consensus)

Recessive Scores

• pRec: 0.221

Intolerance Scores

• loftool: 0.177
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.2

Haploinsufficiency Scores

• pHI: 0.434
• hipred: Y
• hipred_score: 0.736
• ghis: 0.456

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.882

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Paf1

Zebrafish Information Network

• Gene name: paf1
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;endodermal cell fate commitment;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;mRNA polyadenylation;histone monoubiquitination;Wnt signaling pathway;protein ubiquitination;nucleosome positioning;stem cell population maintenance;positive regulation of histone methylation;positive regulation of mRNA 3'-end processing;positive regulation of transcription elongation from RNA polymerase II promoter;histone H2B ubiquitination;protein localization to nucleus;negative regulation of myeloid cell differentiation;positive regulation of transcription by RNA polymerase II;cellular response to lipopolysaccharide;positive regulation of cell cycle G1/S phase transition
• Cellular component: nucleoplasm;cytoplasm;membrane;Cdc73/Paf1 complex;cell junction;transcriptionally active chromatin
• Molecular function: RNA polymerase II complex binding;chromatin binding;protein binding