RPL5

ribosomal protein L5, the group of L ribosomal proteins|Protein phosphatase 1 regulatory subunits|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 1:92832013-92841924

Links

ENSG00000122406 ∙ NCBI:6125 ∙ OMIM:603634 ∙ HGNC:10360 ∙ Uniprot:P46777 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the RPL5 gene.

• 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			2	32	2	36
missense		1	83	2		86
nonsense	16	2				18
start loss	3					3
frameshift	29	7	1			37
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	7	1			11
splice region	2		8	13	1	24
non coding		1	7	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		not specified • Diamond-Blackfan anemia 6 • Diamond-Blackfan anemia 1 • Diamond-Blackfan anemia • 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 (Feb 04, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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

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