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BCL6 COREPRESSOR-LIKE 1; BCORL1

BCL6 COREPRESSOR-LIKE 1; BCORL1

HGNC Approved Gene Symbol: BCORL1Cytogenetic location: Xq26.1 Genomic coordinates (GRCh38): X:129,980,284-130,058,080 (from NCBI)▼ DescriptionThe BCORL1 gene...

HGNC Approved Gene Symbol: BCORL1

Cytogenetic location: Xq26.1 Genomic coordinates (GRCh38): X:129,980,284-130,058,080 (from NCBI)

▼ Description

The BCORL1 gene encodes a transcriptional corepressor that interacts with class II histone acetyltransferases and deacetylases (summary by Schuurs-Hoeijmakers et al., 2013).

▼ Cloning and Expression

Using full-length BRCA1 (113705) as bait in a yeast 2-hybrid screen of a testis cDNA library, Pagan et al. (2007) identified a novel partial cDNA, which they designated BCORL1. They assembled a full-length BCORL1 cDNA and a longer splice variant, designated BCORL1a, encoding deduced 1,711- and 1,785-amino acid proteins, respectively. BCORL1 contains a putative bipartite nuclear localization signal, tandem ankyrin repeats, and a classic CTBP (see 602618)-binding motif, PXDLS. BCORL1 shares homology with the BCOR protein (300485), a transcriptional corepressor for the BCL6 (109565) transcriptional repressor. The human and mouse BCORL1 proteins are about 80% identical. Northern blot analysis of human tissues detected highest expression of BCORL1 in testis and prostate, medium expression in lymphocytes and spleen, and low expression in many other tissues. An antibody raised against the protein showed an approximately 200-kD band consistent with the shorter isoform. A BCORL1-GFP fusion protein demonstrated exclusive localization in nuclei.

▼ Gene Structure

Pagan et al. (2007) determined that the BCORL1 gene contains 13 exons (or 14, depending on alternate splicing) and spans approximately 75 kb.

▼ Mapping

By genomic sequence analysis, Pagan et al. (2007) mapped the BCORL1 gene to chromosome Xq25-q26.1.

▼ Gene Function

Pagan et al. (2007) demonstrated that BCORL1 can act as a corepressor when tethered to DNA. BCORL1 interacted with class II histone deacetylases (HDAC4, 605314; HDAC5, 605315; HDAC7, 606542), suggesting that they are involved in its function as a corepressor. BCORL1 interacted with the CTBP corepressor through the PXDLS motif and affected the repression of E-cadherin (192090), a CTBP target. BCORL1 did not interact with BCL6.

Using a bacterial 2-hybrid system, Junco et al. (2013) found that the C-terminal ubiquitin-like fold domains of PCGF1 (610231) and PCGF3 (617543) interacted with the C-terminal domains of BCOR (300485) and BCORL1.

▼ Molecular Genetics

In 2 Dutch brothers, born of unrelated parents, with Shukla-Vernon syndrome (SHUVER; 301029), Schuurs-Hoeijmakers et al. (2013) identified a hemizygous missense mutation in the BCORL1 gene (N820S; 300688.0001). The variant, which was found by exome sequencing and confirmed by Sanger sequencing, was inherited from the unaffected mother. Schuurs-Hoeijmakers et al. (2013) noted that the BCORL1 gene is expressed in the brain or in neuronal tissue. No functional studies of the variant were performed. The family was 1 of 19 nonconsanguineous families with intellectual disability that underwent exome sequencing.

In 5 boys from 3 families with SHUVER, Shukla et al. (2019) identified hemizygous missense mutations in the BCORL1 gene (300688.0002-300688.0004). The mutations, which were found by whole-exome sequencing, were inherited from mothers who were unaffected or had mild manifestations, such as learning disabilities. Functional studies of the variants and studies of patient cells were not performed.

▼ ALLELIC VARIANTS ( 4 Selected Examples):

.0001 SHUKLA-VERNON SYNDROME
BCORL1, ASN820SER

In 2 Dutch brothers (family W07-1601), born of unrelated parents, with Shukla-Vernon syndrome (SHUVER; 301029), Schuurs-Hoeijmakers et al. (2013) identified a hemizygous c.2459A-G transition (c.2459A-G, NM_021946.4) in the BCORL1 gene, resulting in an asn820-to-ser (N820S) substitution at a highly conserved residue. The variant, which was found by exome sequencing and confirmed by Sanger sequencing, was inherited from the unaffected mother. The mutation was present in less than 1% of dbSNP (build 134) samples and in less than 1% of 672 in-house exomes. Schuurs-Hoeijmakers et al. (2013) noted that the BCORL1 gene is expressed in the brain or in neuronal tissue. No functional studies of the variant were performed. The patients had coarse facial features and hypotonia. The family was 1 of 19 nonconsanguineous families with intellectual disability that underwent exome sequencing.

.0002 SHUKLA-VERNON SYNDROME
BCORL1, VAL782GLU

In a 15-year-old boy (patient 1) with Shukla-Vernon syndrome (SHUVER; 301029), Shukla et al. (2019) identified a hemizygous c.2345T-A transversion (c.2345T-A, NM_021946.4) in the BCORL1 gene, resulting in a val782-to-glu (V782E) substitution at a conserved residue in a putative DNAse hypersensitivity region. The mutation, which was found by whole-exome sequencing, was inherited from the mother, who had learning disabilities, anxiety, and ADHD. The variant was found in 1 individual in the hemizygous state in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed.

.0003 SHUKLA-VERNON SYNDROME
BCORL1, SER496PHE

In a 7-year-old boy (patient 2) with Shukla-Vernon syndrome (SHUVER; 301029), Shukla et al. (2019) identified a hemizygous c.1487C-T transition (c.1487C-T, NM_021946.4) in the BCORL1 gene, resulting in a ser496-to-phe (S496F) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing, was inherited from the mother, who had chronic pain and joint hypermobility. The variant was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed.

.0004 SHUKLA-VERNON SYNDROME
BCORL1, PRO32LEU

In 3 sibs (family 3), born of unrelated Indian parents, with Shukla-Vernon syndrome (SHUVER; 301029), Shukla et al. (2019) identified a hemizygous c.95C-T transition (c.95C-T, NM_021946.4) in the BCORL1 gene, resulting in a pro32-to-leu (P32L) substitution at a highly conserved residue in a putative DNAse hypersensitivity region. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was inherited from the mother. The variant was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed.

Tags: Xq26.1