RPS19
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
RPS19 (HGNC:10402) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
ribosomal protein S19
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
LOH19CR1
Alias symbols
S19, eS19, DBA
%HI
23.95(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.24(Read more about gnomAD LOEUF score)
Cytoband
19q13.2
Genomic Coordinates
GRCh37/hg19: chr19:42364325-42376993 NCBI Ensembl UCSC
GRCh38/hg38: chr19:41860255-41872925 NCBI Ensembl UCSC
MANE Select Transcript
NM_001022.4 ENST00000598742.6 (Read more about MANE Select)
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 pre- rRNA processing and maturation of 40S ribosomal subunits (PubMed:16990592). 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 ribos... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-31877
ClinGen Curation ID:
CCID:007785
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
03/24/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • DIAMOND-BLACKFAN ANEMIA 1; DBA1 Monarch
HI Evidence:
  • PUBMED: 10590074
    Willig et al. in 1999 were the first to describe the relationship between Diamond-Blackfan anemia (DBA) and RPS19 loss of functions variants. They described 11 nonsense variants and 15 indels. They also described several RPS19 missense mutations, splicing defects and intronic variants in individuals with similar phenotypes. Most of those patients had DBA without other clinical manifestations, and they were all considered sporadic cases with confirmed de novo variants. A minority of cases also presented facial malformations, head circumference alterations, intellectual disability, kidney malformation and short stature.
  • PUBMED: 15384984
    Gazda et al. in 2004 described several patients with Diamond-Blackfan anemia and loss of function (LoF) variants. Among those patients, 14 different variants were identified, including seven de novo LoF variants. They also demonstrated those variants reduced RPS19 mRNA and protein levels in CD34+ bone marrow cells suggesting haploinsufficiency as a disease mechanism.
  • PUBMED: 15059149
    Orfali et al. in 2004 described 104 families from United Kingdom with DBA including 16 (15%) with RPS19 variants, including 4 de novo loss of function variants.
  • PUBMED: 20960466
    Boria et al. in 2010 described a DBA Mutation Database consisting in hundreds of variants in 9 different genes including RPS19, which is the most frequently mutated gene in patients with DBA. The DBA Mutation Database registered 129 distinct RPS19 variants carried by 219 patients: 82 of these are de novo and 45 are inherited. The authors themselves reported several additional variants, including 3 nonsense,18 indels and 10 splice-site defects.
HI Evidence Comments:
Whole gene deletions, as well as intragenic mutations of RPS19, are known to cause Diamond-Blackfan anemia by a pathogenic mechanism of haploinsufficiency. See GeneReviews for relevant primary literature and review.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000019.9) (NC_000019.10)