LEO1

LEO1 homolog, Paf1/RNA polymerase II complex component, the group of Paf1/RNA polymerase II complex

Basic information

Region (hg38): 15:51938025-51971778

Links

ENSG00000166477 ∙ NCBI:123169 ∙ OMIM:610507 ∙ HGNC:30401 ∙ Uniprot:Q8WVC0 ∙ 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 LEO1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LEO1 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						0
missense			47	1		48
nonsense		1				1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	1	48	1	0

Variants in LEO1

This is a list of pathogenic ClinVar variants found in the LEO1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-51938168-T-A		LEO1-related disorder	Likely benign (Jun 24, 2019)
15-51938202-T-C		not specified	Uncertain significance (Jul 06, 2024)
15-51938221-C-T		not specified	Uncertain significance (Aug 13, 2021)
15-51938228-T-A			Uncertain significance (Oct 21, 2021)
15-51941565-C-A		LEO1-related disorder	Likely benign (Feb 24, 2022)
15-51947343-T-G		not specified	Uncertain significance (Mar 02, 2023)
15-51947361-G-A		LEO1-related disorder	Benign (Feb 20, 2019)
15-51949885-C-T		LEO1-related disorder	Uncertain significance (Sep 16, 2022)
15-51949918-C-T		not specified	Uncertain significance (Jun 07, 2023)
15-51949925-G-A		not specified	Uncertain significance (Aug 20, 2024)
15-51949936-C-T		not specified	Uncertain significance (Nov 09, 2024)
15-51949945-C-T		not specified	Uncertain significance (Jul 20, 2021)
15-51951888-T-C		not specified	Uncertain significance (Jun 11, 2021)
15-51951936-A-G			Uncertain significance (Apr 17, 2023)
15-51951977-G-C			Uncertain significance (May 12, 2023)
15-51953193-G-T			Uncertain significance (Mar 30, 2023)
15-51953241-C-T		not specified	Uncertain significance (Jun 03, 2024)
15-51953258-G-A		not specified	Uncertain significance (Mar 20, 2023)
15-51953266-G-A		LEO1-related disorder	Likely benign (Apr 11, 2019)
15-51954544-C-T		not specified	Uncertain significance (Aug 13, 2021)
15-51954547-C-G		not specified	Uncertain significance (May 24, 2023)
15-51954563-T-C		not specified	Uncertain significance (May 03, 2023)
15-51958747-A-G		LEO1-related disorder	Benign (May 20, 2019)
15-51958756-T-C			Uncertain significance (Jan 24, 2024)
15-51959920-T-C		LEO1-related disorder	Uncertain significance (Mar 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LEO1	protein_coding	protein_coding	ENST00000299601	12	33782

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.871	0.129	125735	0	10	125745	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.34	241	367	0.656	0.0000195	4485
Missense in Polyphen		38	104.6	0.36329		1335
Synonymous	0.643	121	130	0.928	0.00000715	1138
Loss of Function	4.62	7	37.5	0.187	0.00000219	432

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000551	0.0000544
Finnish	0.0000467	0.0000462
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.0000551	0.0000544
South Asian	0.0000665	0.0000653
Other	0.00	0.00

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. Involved in polyadenylation of mRNA precursors. Connects PAF1C to Wnt signaling. {ECO:0000269|PubMed:15632063, ECO:0000269|PubMed:15791002, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742}.
• Pathway: Endoderm Differentiation;Signaling by WNT;Signal Transduction;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;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.159

Intolerance Scores

• loftool: 0.0456
• rvis_EVS: -1.11
• rvis_percentile_EVS: 6.72

Haploinsufficiency Scores

• pHI: 0.165
• hipred: Y
• hipred_score: 0.816
• ghis: 0.666

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.456

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Leo1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: leo1
• Affected structure: xanthophore
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: 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;stem cell population maintenance;positive regulation of mRNA 3'-end processing;positive regulation of transcription elongation from RNA polymerase II promoter;histone H2B ubiquitination;negative regulation of myeloid cell differentiation;positive regulation of transcription by RNA polymerase II;beta-catenin-TCF complex assembly
• Cellular component: fibrillar center;nucleus;nucleoplasm;centrosome;Cdc73/Paf1 complex
• Molecular function: protein binding;RNA polymerase II C-terminal domain phosphoserine binding