GeneBe

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.

  • not_specified (37 variants)
  • not_provided (4 variants)
  • Peroxisome_biogenesis_disorder_1A_(Zellweger) (1 variants)

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. These statistics are base on transcript: NM_000019088.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
 2
missense
37
clinvar
 37
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total 0 0 38 2 0
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PAF1protein_codingprotein_codingENST00000221265 145344
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.0001691.001257250231257480.0000915
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.751733090.5590.00001913582
Missense in Polyphen2898.3850.28461134
Synonymous-0.08011131121.010.00000720911
Loss of Function3.191231.20.3840.00000180351

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00008670.0000867
Ashkenazi Jewish0.00009920.0000992
East Asian0.0003260.000326
Finnish0.00004620.0000462
European (Non-Finnish)0.00006170.0000615
Middle Eastern0.0003260.000326
South Asian0.0001370.000131
Other0.0001630.000163

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Paf1
Phenotype

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