Alternative titles; symbols
HGNC Approved Gene Symbol: PSMB1
Cytogenetic location: 6q27 Genomic coordinates (GRCh38): 6:170,535,120-170,553,307 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6q27 | ?Neurodevelopmental disorder with microcephaly, hypotonia, and absent language | 620038 | Autosomal recessive | 3 |
The PSMB1 gene encodes the beta-6 subunit of the proteasome beta-type family that is part of the 20S and 26S proteasomes, which are responsible for the breakdown of intracellular proteins (summary by Ansar et al., 2020).
See PSMB2 (602175) for further discussion of this gene family.
Tamura et al. (1994) isolated 2 human proteasome genes encoding the alpha-type HC3 (PSMA2; 176842) and the beta-type HC5 subunits. Analysis of their promoter sequences revealed the absence of TATA and CAAT elements and the existence of 2 or 3 GC boxes that function coordinately as promoters of the 2 genes. Differences in the exon/intron organizations of these genes, however, suggested that they diverged at an early stage of evolution.
Trachtulec et al. (1997) mapped the human PSMB1 gene to a region of chromosome 6q27 syntenic with the proximal part of mouse chromosome 17, where the mouse homolog maps. In both human and mouse PSMB1 is tightly linked to the TATA-binding protein gene (TBP; 600075). The 2 genes are transcribed in the opposite orientation in both species.
The TATA-binding protein (TBP) is a factor required for the transcription of all classes of eukaryotic genes. The human TBP and mouse Tbp are single-copy genes; in Drosophila TATA-binding protein genes, the housekeeping Tbp and the developmentally regulated Trf, map to opposite arms of the second chromosome. Trachtulec et al. (1997) demonstrated in the mouse that the Tbp gene resides next to the proteasomal subunit C5-encoding gene (Psmb1). The genes are located on mouse chromosome 17 in the t complex within the 'Hybrid sterility 1' (Hst1) region. They also demonstrated that the homologous human genes, TBP and PSMB1, are tightly linked on chromosome 6q27 in a region syntenic with the proximal part of mouse chromosome 17. The TATA-binding protein and proteasomal subunit C5 genes are also linked on chromosome III of C. elegans, and together they are linked to other genes whose homologs map to human chromosome 6 and mouse chromosome 17. In Drosophila, the 2 housekeeping TATA-binding protein genes map close to 2 other genes with homologs in the mammalian major histocompatibility complex. Thus, Trachtulec et al. (1997) concluded that there exists conserved synteny of unrelated genes between mammals and invertebrates.
In 2 sisters, born of consanguineous Pakistani parents (family F200), with neurodevelopmental disorder with microcephaly, hypotonia, and absent language (NEDMHAL; 620038), Ansar et al. (2020) identified a homozygous missense mutation in the PSMB1 gene (Y103H; 602017.0001). The mutation, which was found by a combination of exome sequencing and homozygosity mapping and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the gnomAD database or in 300 local controls. Western blot analysis indicated that the mutant protein was not processed into its shorter mature form, which resulted in impaired assembly and function of the 20S and 26S proteasomes when expressed in human SHSY5Y neuroblastoma cells. The findings were consistent with a hypomorphic allele.
Ansar et al. (2020) found that CRISPR/Cas9- and morpholino-mediated knockdown of the psmb1 ortholog in zebrafish embryos resulted in microcephaly, microphthalmia, and edema around the eyes and the pericardium. These changes were accompanied by an overall reduction in brain size and morphologic brain abnormalities.
Okumura et al. (1995) mapped the PSMB1 gene to chromosome 7p13-p12 by fluorescence in situ hybridization.
In 2 sisters, born of consanguineous Pakistani parents (family F200), with neurodevelopmental disorder with microcephaly, hypotonia, and absent language (NEDMHAL; 620038), Ansar et al. (2020) identified a homozygous c.307T-C transition (c.307T-C, NM_002793.4) in the PSMB1 gene, resulting in a tyr103-to-his (Y103H) substitution at a highly conserved residue. The mutation, which was found by a combination of exome sequencing and homozygosity mapping and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the gnomAD database or in 300 local controls. Western blot analysis indicated that the mutant protein was not processed into its shorter mature form, which resulted in impaired assembly and function of the 20S and 26S proteasomes when expressed in human SHSY5Y neuroblastoma cells. The findings were consistent with a hypomorphic allele.
Ansar, M., Ebstein, F., Ozkoc, H., Paracha, S. A., Iwaszkiewicz, J., Gesemann, M., Zoete, V., Ranza, E., Santoni, F. A., Sarwar, M. T., Ahmed, J., Kruger, E., Bachmann-Gagescu, R., Antonarakis, S. E. Biallelic variants in PSMB1 encoding the proteasome subunit beta-6 cause impairment of proteasome function, microcephaly, intellectual disability, developmental delay and short stature. Hum. Molec. Genet. 29: 1132-1143, 2020. [PubMed: 32129449] [Full Text: https://doi.org/10.1093/hmg/ddaa032]
Okumura, K., Nogami, M., Taguchi, H., Hisamatsu, H., Tanaka, K. The genes for the alpha-type HC3 (PMSA2) and beta-type HC5 (PMSB1) subunits of human proteasomes map to chromosomes 6q27 and 7p12-p13 by fluorescence in situ hybridization. Genomics 27: 377-379, 1995. [PubMed: 7558012] [Full Text: https://doi.org/10.1006/geno.1995.1062]
Tamura, T., Osaka, F., Kawamura, Y., Higuti, T., Ishida, N., Nothwang, H.-G., Tsurumi, C., Tanaka, K., Ichihara, A. Isolation and characterization of alpha-type HC3 and beta-type HC5 subunit genes of human proteasomes. J. Molec. Biol. 244: 117-124, 1994. [PubMed: 7966316] [Full Text: https://doi.org/10.1006/jmbi.1994.1710]
Trachtulec, Z., Hamvas, R. M. J., Forejt, J., Lehrach, H. R., Vincek, V., Klein, J. Linkage of TATA-binding protein and proteasome subunit C5 genes in mice and humans reveals synteny conserved between mammals and invertebrates. Genomics 44: 1-7, 1997. [PubMed: 9286694] [Full Text: https://doi.org/10.1006/geno.1997.4839]