UBE2A |
- 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)
Haploinsufficiency (HI) Score Details
- syndromic X-linked intellectual disability Nascimento type Monarch
-
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.
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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.
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
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.