Infertility and Recurrent Pregnancy Loss
Gene: BCORL1
i) PMID: 38342987- novel hemizygous nonsense variant (c.1564G > T:p.Glu522*) in a male patient with oligoasthenoteratozoospermia (OAT) from a Han Chinese family. Functional analysis showed that the variant produced a truncated protein with altered cellular localization and a dysfunctional interaction with SKP1 (S-phase kinase-associated protein 1). Also identified four hemizygous missense variants (c.2615T > G:p.Val872Gly, c.2669G > A:p.Arg890Gln, c.3164A > G:p.Asp1055Gly and c.3344C > T:p.Pro1115Leu) in subjects with both OAT (1 of 325, 0.31%) and NOA (4 of 355, 1.13%). They hypothesized that the BCORL1 (c.2615 T > G, c.2669G > A, c.3164A > G, c.3344C > T) missense mutations may have led to an accumulation of dysfunctional toxic proteins that resulted in a more severe male infertility phenotype in the patient (NOA).
ii) PMID: 32376790- Hemizygous missense variant in a male patient with NOA without other diseases, which also found that the knockout of Bcorl1 in mice resulted in OAT with the abnormal brain development. It had not been previously linked to male infertility. This study demonstrates, for the first time, that loss of Bcorl1 causes spermatogenesis failure.
iii) PMID: 39267058- hemizygous missense variant (p.Arg19Gln) in a infertile male with oliogasthenozoospermia, no functional data
iv) PMID: 39189935- novel hemizygous missense variant (p.G1391R) and a recurrent variant (p.V872G) in BCORL1 from four OAT patients. Functional assays showed that the variants disturb the transcription of spermatogenetic genes such as SYCE1 and DAZL, impair the interaction with HDAC7, and cause epigenetic changes such as changes in level of histone modification with different extent, including the enhancement in acetylation of H3K14, and the reduction in acetylation of H4K5 and H4K8.
Sources: LiteratureCreated: 30 May 2025, 1:57 a.m. | Last Modified: 30 May 2025, 1:58 a.m.
Panel Version: 0.82
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Spermatogenic failure
Publications
Gene: bcorl1 has been classified as Green List (High Evidence).
Phenotypes for gene: BCORL1 were changed from Spermatogenic failure to Spermatogenic failure, MONDO:0004983, BCORL1-related
Gene: bcorl1 has been classified as Green List (High Evidence).
gene: BCORL1 was added gene: BCORL1 was added to Infertility and Pregnancy Loss. Sources: Literature Mode of inheritance for gene: BCORL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: BCORL1 were set to 38342987; 32376790; 39267058; 39189935 Phenotypes for gene: BCORL1 were set to Spermatogenic failure Review for gene: BCORL1 was set to GREEN