Alt. symbols: CGI-97 | FLJ10917 | SDS | SWDS

Approved name: SBDS ribosome maturation factor
Alt. names: Shwachman-Bodian-Diamond syndrome, SBDS, ribosome assembly guanine nucleotide exchange factor

Location: 7q11.21: 66987680 - 66995693 (-)
Gene type: protein_coding, 13 transcripts.

Scores: LoFtool: 0.375000 | pLI: 0.11926362 | LOEUF: 1.225

HGNC: 19440

NCBI: 51119, RefSeq: NG_007277.1

Ensembl: ENSG00000126524.12

LRG_104 | Status: public

OMIM: 607444

Expression | ProteinAtlas

The SBDS gene encodes a ribosome maturation protein that is critical for ribosome biogenesis. Together with EFL1, the SBDS protein assists in the assembly of the large ribosomal subunit by triggering the release of the EIF6 protein from 60S pre-ribosomes in the cytoplasm. EIF6 blocks the interaction of the large subunit with the small subunit. Once EIF6 is released, 80S ribosome assembly occurs and ribosomes are ready for translation; at the same time, EIF6 is recycled to the nucleus, where it is required for 60S rRNA processing and nuclear export. Therefore, SBDS is required for normal levels of protein synthesis, but it may also play a role in cellular stress resistance, cellular response to DNA damage, RNA processing, and cell proliferation.

Mutations in SBDS were first reported to be associated with autosmal recessive Shwachman-Diamond syndrome (SDS) by Boocock and colleagues (Nat. Genet., 2004). In a cohort of 158 index cases with SDS, mutations in SBDS were detected in 141 of individuals. To date, the most prevalent mutation is the splice-site variant c.258+2T>C in intron 2 of the gene, which was initially detected in homozygosity in 7 cases, and in compound heterozygosity with the c.183-184delTAinsCT mutation in 79 cases, as wel l as with a different SBDS mutation in 44 cases (Boocock et al., 2004). In addition, there were 8 cases found to carry the c.258+2T>C mutation on one allele and both (c.258+2T>C and c.183-184delTAinsCT) mutations on the second allele. The mutations c.258+2T>C and c.183-184delTAinsCT resulted from gene conversion between a SBDS pseudogene (SBDSP) and SBDS, which are 97% identical. Both mutations resulted in premature stop codons (p.Cys84fs3, p.Lys62) and thus lack of protein synthesis. The additional frameshift and missense mutations reported, such as p.Asn8Lys, p.Asn34fs*15, p.Glu44Gly, p.Lys67Glu, p.Ile87Ser, p.Arg126Thr, p.Arg169Cys, and p.Ile212Thr, did not result from gene conversion, but normal mutation events. Subsequent studies have reported additional SDS patients with different mutations: Nakashima, et al. (Hum. Genet., 2004) identified 5 Japanese SDS cases carrying the c.258+2T>C mutation in compound heterozygosity with other mutations, which also resulted from gene conversion. Kuijpers et al. (Blood, 2015) identified SBDS mutations in 15 of 20 SDS patients, 11 of which carried the same genotype: [c.258+2T>C / c.183-184delTAinsCT]. Interestingly, the common c.258+2T>C mutation has been associated in simple heterozygosity with susceptibility to aplastic anemia (AA) (Calado, R. et al. 2007). These authors reported 4 carriers out of 91 patients with apparently acquired AA, who showed reduced SBDS expression but no evidence of the pancreatic exocrine failure or skeletal abnormalities typical of SDS. More recently, a single case of SDS carrying a missense variant (p.K33T) and a structural variant in the other allele of SBDS was reported (Carvalho et al. 2014). [Load More]