RPS24

Gene Facts

• HGNC Symbol: RPS24 (HGNC:10411)
• HGNC Name: ribosomal protein S24
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: No previous names found
• Alias symbols: S24, eS24
• %HI: 22.8
• pLI: 1
• LOEUF: 0.18
• Cytoband: 10q22.3
• Genomic Coordinates:

  GRCh37/hg19:	chr10:79793621-79816564
  GRCh38/hg38:	chr10:78033863-78056806

• MANE Select Transcript: NM_033022.4 ENST00000372360.9
• Function: Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Required for processing of pre-rRNA and maturation of 40S ribosomal subunits (PubMed:18230666). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and rib... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-30750
• ClinGen Curation ID: CCID:007786
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Sufficient Evidence for Haploinsufficiency (3)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Last Evaluated: 10/23/2019

Haploinsufficiency (HI) Score Details

• HI Score: 3
• HI Evidence Strength: Sufficient Evidence for Haploinsufficiency

HI Disease

• Diamond-Blackfan anemia 3

HI Evidence

• PUBMED: 23812780
  Landowski et al. 2013 studied 87 unrelated patients with a clinical diagnosis of Diamond Blackfan Anemia (DBA) (thought to be a disorder of ribosome biogenesis and/or function); all patients had previously had negative sequencing studies of all currently known ribosomal protein (RP) genes. The authors screened the patients using an array with enriched coverage over known RP genes and 117 additional genes "shown to be involved in human ribosomal biogenesis or homologous to yeast pre-ribosomal factors." They identified 6 deletions in RP genes amongst 6 patients, including a de novo 1.7kb deletion in RPS24 including exons 1, 2, and part of 3. The authors showed that pre-ribosomal RNA processing was affected in cell lines established from patient cells.
• PUBMED: 17186470
  Gazda et al. 2006: The authors describe a cohort of 185 unrelated probands (representing both familial and sporadic cases) with clinical diagnoses of DBA and no known pathogenic mutations in the RPS19 gene. Following linkage studies in an extensive family with 10 informative meioses, the authors identified a heterozygous nonsense variant in exon 4 of RPS24 cosegregating with disease. The authors then sequenced RPS24 in the rest of the cohort, identifying another nonsense variant in exon 2 and a splice site variant resulting in skipping of exon 2 in two unrelated probands. These three variants were not found when the authors sequenced RPS24 in 210 ethnically matched controls. The authors report that "qrt-PCR showed a reduced level of total RPS24 mRNA from lymphoblastoid cell lines in both probands...with nonsense mutations... and premature stop codons, suggesting degradation of mutated transcript due to nonsense-mediated decay." Additional functional studies on RPS24 suggesting it causes DBA through loss-of-function mechanisms are reported by this group in PMID: 18230666. PMID: 29044489 Arbiv et al. 2018: The authors studied a cohort of 74 patients diagnosed with DBA. A frameshift variant (c.66_67delAA) of RPS24 was found in one patient. PMID: 25946618 Smetanina et al. 2015: A sporadic mutation in the RPS24 gene was identified in one DBA case. It was a donor splicing site mutation at intron 1 (c.3+1G>T). PMID: 19689926 Badhai et al. 2009: Primary fibroblasts from DBA patients with a truncating mutation (c.1A>G, p.M1?) in RPS24 have a marked reduction in proliferative capacity. Authors suggest that their functional evidence demonstrates that the RPS24 variant results in haploinsufficiency. PMID: 26136524 Ghemlas et al. 2015: Among 75 inherited bone marrow failure syndromes (IBMFSs) patients with clinically classified IBMFSs, they identified a nucleotide-level causal mutation (c.4-2A>G splicing variant) in one DBA patient. The same variant (c.1A>G, p.Met1?) with Badhai et al 2009, which causing start codon lost was also found in another patient. PMID: 20960466 Boria et al. 2010: The authors reported a mutation update for DBA that includes a sporadic donor splice donor variant (c.390+1G>A, p.0?) of RPS24.

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity