• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
UBE2A (HGNC:12472) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
ubiquitin conjugating enzyme E2 A
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
UBC2, HHR6A, RAD6A, HR6A
%HI
9.57(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.82(Read more about gnomAD pLI score)
LOEUF
0.54(Read more about gnomAD LOEUF score)
Cytoband
Xq24
Genomic Coordinates
GRCh37/hg19: chrX:118708526-118718386 NCBI Ensembl UCSC
GRCh38/hg38: chrX:119574563-119584423 NCBI Ensembl UCSC
MANE Select Transcript
NM_003336.4 ENST00000371558.7 (Read more about MANE Select)
Function
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys- 120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-8717
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
05/22/2019

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • syndromic X-linked intellectual disability Nascimento type Monarch
HI Evidence:
  • PUBMED: 16909393
    Nascimento (2006): A report of a family with syndromic X-linked intellectual disability where affected males had a nonsense mutation in the 3' end of UBE2A. The female carriers were phenotypically normal and had skewed X-inactivation. A normal non-carrier sister had random X-inactivation. Functional studies were not provided and it is not known if this mutation leads to a protein-degradation.
  • PUBMED: 23685073
    Haddad (2013) reported 5 affected males among 2 families. One family with frameshift mutation leading to deletion and the other with a missense mutation affecting highly conserved amino acid in exon 1. Neither was seen in 389 controls. All males had ID and other developmental features.
  • PUBMED: 24053514
    Czeschik 2013 reported 8 affected males among 5 families. Patient 6 was found to have a de novo nonsense mutation in exon 6 and presented with intellectual disabilities, skin changes, facial dysmorphism, urogenital anomalies, seizures, heart defect, and additional clinical features. Patients 1-3 from Family A were found to have an intragenic deletion encompassing exons 1-3 of UBE2A. These patients presented with characteristic facial features, severe intellectual disabilities, skin changes, and additional variable features. The remaining families presented with very similar phenotypes and variable missense mutations or non-focal deletions including UBE2A. Additional carrier females were typically phenotypically normal and found to have skewed X inactivation.
HI Evidence Comments:
de Leeuw 2010 (21108393) reports an additional 3 families, 3 patients with similar deletions encompassing SLC25A43,SLC25A5,CXorf56,UBE2A,NKRF, and two non-coding RNA genes,U1andLOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures,and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. Though these deletions were not focal to UBE2A, the clinical and dysmorphic features significantly overlapped those observed in males with missense mutations in the literature. 3 female carriers were tested and all had 90%+ skewing.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)