RPL5
Basic information
Region (hg38): 1:92832012-92841924
Links
Phenotypes
GenCC
Source:
- Diamond-Blackfan anemia 6 (Strong), mode of inheritance: AD
- Diamond-Blackfan anemia (Supportive), mode of inheritance: AD
- Diamond-Blackfan anemia 6 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Diamond-Blackfan anemia 6 | AD | Cardiovascular; Hematologic; Oncologic | Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may allow early detection and management; Individuals with DBA may manifest a variety of congenital malformations (eg, cardiac anomalies), and awareness may allow prompt detection and management | Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Oncologic; Renal | 16317735; 5764780; 19061985; 20301769; 23718193; 23812780 |
ClinVar
This is a list of variants' phenotypes submitted to
- Diamond-Blackfan anemia (37 variants)
- not provided (12 variants)
- Diamond-Blackfan anemia 6 (8 variants)
- Diamond-Blackfan anemia 1 (1 variants)
- 17 conditions (1 variants)
- Inborn genetic diseases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPL5 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 32 | 36 | ||||
missense | 83 | 86 | ||||
nonsense | 16 | 18 | ||||
start loss | 3 | |||||
frameshift | 29 | 37 | ||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 11 | |||||
splice region | 2 | 8 | 13 | 1 | 24 | |
non coding | 34 | 13 | 55 | |||
Total | 51 | 18 | 95 | 68 | 15 |
Variants in RPL5
This is a list of pathogenic ClinVar variants found in the RPL5 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
1-92832041-C-A | Diamond-Blackfan anemia 6 | Uncertain significance (Jan 13, 2018) | ||
1-92832045-T-A | Diamond-Blackfan anemia 6 | Uncertain significance (Jan 12, 2018) | ||
1-92832051-C-G | Diamond-Blackfan anemia 6 | Uncertain significance (Jan 13, 2018) | ||
1-92832053-C-G | Diamond-Blackfan anemia 6 | Likely benign (Jan 12, 2018) | ||
1-92832057-G-T | Diamond-Blackfan anemia 6 | Benign (Sep 01, 2022) | ||
1-92832060-C-G | Diamond-Blackfan anemia 6 | Benign (Jan 13, 2018) | ||
1-92832063-C-G | Diamond-Blackfan anemia 6 | Benign (Jan 13, 2018) | ||
1-92832067-G-A | Diamond-Blackfan anemia 6 | Benign (Jan 12, 2018) | ||
1-92832069-C-A | not provided (-) | |||
1-92832069-C-G | Diamond-Blackfan anemia 6 | Uncertain significance (Jan 12, 2018) | ||
1-92832073-A-C | Diamond-Blackfan anemia 6 | Benign (Jan 12, 2018) | ||
1-92832077-C-T | Diamond-Blackfan anemia 6 | Likely benign (Jan 13, 2018) | ||
1-92832097-C-A | Diamond-Blackfan anemia 6 | Benign (Jan 13, 2018) | ||
1-92832109-C-T | Diamond-Blackfan anemia 6 • not specified | Likely benign (May 09, 2022) | ||
1-92832113-G-A | Diamond-Blackfan anemia 6 | Uncertain significance (Jan 13, 2018) | ||
1-92832115-A-C | Diamond-Blackfan anemia | Pathogenic (Jan 06, 2020) | ||
1-92832115-A-G | Pathogenic (Feb 04, 2022) | |||
1-92832116-T-G | Diamond-Blackfan anemia | Pathogenic (Aug 22, 2022) | ||
1-92832117-G-A | Diamond-Blackfan anemia | Pathogenic (Jul 09, 2015) | ||
1-92832118-G-A | Diamond-Blackfan anemia 6 | Pathogenic/Likely pathogenic (May 04, 2023) | ||
1-92832120-G-A | Diamond-Blackfan anemia | Uncertain significance (Jul 28, 2023) | ||
1-92832120-G-C | Diamond-Blackfan anemia • not specified • Diamond-Blackfan anemia 6 • Diamond-Blackfan anemia 1 • RPL5-related disorder | Benign/Likely benign (Jan 29, 2024) | ||
1-92832120-G-T | Diamond-Blackfan anemia | Uncertain significance (Nov 10, 2020) | ||
1-92832122-G-A | Diamond-Blackfan anemia | Uncertain significance (May 29, 2022) | ||
1-92832122-G-C | Diamond-Blackfan anemia | Uncertain significance (Jun 11, 2023) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
RPL5 | protein_coding | protein_coding | ENST00000370321 | 8 | 9900 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.998 | 0.00224 | 0 | 0 | 0 | 0 | 0.00 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.90 | 101 | 171 | 0.591 | 0.00000942 | 1962 |
Missense in Polyphen | 29 | 55.428 | 0.5232 | 679 | ||
Synonymous | -0.288 | 58 | 55.3 | 1.05 | 0.00000280 | 539 |
Loss of Function | 3.92 | 0 | 17.9 | 0.00 | 0.00000111 | 208 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00 | 0.00 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.00 | 0.00 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.00 | 0.00 |
Middle Eastern | 0.00 | 0.00 |
South Asian | 0.00 | 0.00 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl- transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs (PubMed:12962325, PubMed:19061985, PubMed:24120868, PubMed:23636399). It also couples ribosome biogenesis to p53/TP53 activation. As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53 (PubMed:24120868). {ECO:0000269|PubMed:12962325, ECO:0000269|PubMed:19061985, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:24120868}.;
- Disease
- DISEASE: Diamond-Blackfan anemia 6 (DBA6) [MIM:612561]: A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. {ECO:0000269|PubMed:19061985, ECO:0000269|PubMed:19191325}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Ribosome - Homo sapiens (human);Cytoplasmic Ribosomal Proteins;SRP-dependent cotranslational protein targeting to membrane;Eukaryotic Translation Initiation;Eukaryotic Translation Termination;Translation;Selenocysteine synthesis;Metabolism of proteins;Metabolism of amino acids and derivatives;Metabolism of RNA;Formation of a pool of free 40S subunits;Metabolism;Nonsense-Mediated Decay (NMD);Selenoamino acid metabolism;Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);L13a-mediated translational silencing of Ceruloplasmin expression;Peptide chain elongation;Eukaryotic Translation Elongation;GTP hydrolysis and joining of the 60S ribosomal subunit;Cap-dependent Translation Initiation;p53 pathway
(Consensus)
Recessive Scores
- pRec
- 0.206
Intolerance Scores
- loftool
- rvis_EVS
- -0.03
- rvis_percentile_EVS
- 51.4
Haploinsufficiency Scores
- pHI
- 0.263
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.595
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.961
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rpl5
- Phenotype
Zebrafish Information Network
- Gene name
- rpl5a
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- ribosomal large subunit assembly;nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;rRNA processing;translation;translational initiation;SRP-dependent cotranslational protein targeting to membrane;positive regulation of gene expression;ribosomal large subunit biogenesis;positive regulation of translation;protein stabilization;regulation of signal transduction by p53 class mediator;negative regulation of ubiquitin protein ligase activity;negative regulation of ubiquitin-dependent protein catabolic process;negative regulation of protein neddylation
- Cellular component
- nucleus;nucleoplasm;nucleolus;cytoplasm;endoplasmic reticulum;cytosol;focal adhesion;membrane;cytosolic large ribosomal subunit;protein-containing complex;extracellular exosome;ribonucleoprotein complex
- Molecular function
- RNA binding;mRNA 3'-UTR binding;structural constituent of ribosome;protein binding;5S rRNA binding;ubiquitin protein ligase binding;mRNA 5'-UTR binding;ubiquitin ligase inhibitor activity