GeneBe

LEO1

protein-coding

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

Gene summary

LEO1, parafibromin (CDC73; MIM 607393), CTR9 (MIM 609366), and PAF1 (MIM 610506) form the PAF protein complex that associates with the RNA polymerase II subunit POLR2A (MIM 180660) and with a histone methyltransferase complex (Rozenblatt-Rosen et al., 2005 [PubMed 15632063]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_138792.4

Inheritance

AD

ClinVar variants

P:3U:99B:10

Top phenotype

LEO1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr15:51,938,025-51,971,778

External References & Databases

Ensembl (ENSG00000166477)NCBI Gene (123169)OMIM (610507)HGNC:30401GenCCUniProt (Q8WVC0)AlphaFoldClinVar (LEO1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~33.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LEO1 variants in ClinVar

5 Conditions Cataloged
not specifiedTotal: 68
not providedTotal: 31
LEO1-related disorderTotal: 14
Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 1
LEO1-related neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138792.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
3
clinvar
 7
missense
2
clinvar
90
clinvar
3
clinvar
1
clinvar
 96
nonsense
1
clinvar
5
clinvar
 6
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total039964112
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_138792.4RefSeqNP_620147.112MANE Select
ENST00000299601.10EnsemblENSP00000299601.512MANE Select
NM_001286430.2RefSeqNP_001273359.110Standard
NM_001323903.2RefSeqNP_001310832.113Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
leo1Danio rerio

Structure: xanthophore

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Endoderm Differentiation
  • Signaling by WNT
  • Signal Transduction
  • Gene expression (Transcription)
  • RNA Polymerase II Pre-transcription Events

Biological Process

  • endodermal cell fate commitment
  • transcription by RNA polymerase II
  • transcription elongation from RNA polymerase II promoter
  • mRNA polyadenylation
  • histone monoubiquitination

Molecular Function

  • protein binding
  • RNA polymerase II C-terminal domain phosphoserine binding

Cellular Component

  • fibrillar center
  • nucleus
  • nucleoplasm
  • centrosome
  • Cdc73/Paf1 complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000299601
Coding exons
12
Length
33782
Individuals with no LoFs
125735
Homozygous LoFs
0
Heterozygous LoFs
10
Defined
125745
p
0.0000398
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.342413670.6560.00001954485
Missense (PolyPhen)38104.60.363291335
Synonymous0.6431211300.9280.000007151138
Loss of Function4.62737.50.1870.00000219432

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.0000550.000054rare
Finnish0.0000470.000046rare
European (Non-Finnish)0.0000530.000053rare
South Asian0.0000660.000065rare
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.159

Intolerance Scores

LoFtool
0.0456
RVIS EVS
-1.11
RVIS percentile EVS
6.72

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
E
Indispensability pred.
N
Indispensability score
0.456

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.