RPS26

ribosomal protein S26, the group of S ribosomal proteins

Basic information

Region (hg38): 12:56041350-56044697

Links

ENSG00000197728 ∙ NCBI:6231 ∙ OMIM:603701 ∙ HGNC:10414 ∙ Uniprot:P62854 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed

Phenotypes

GenCC

Source: genCC

• Diamond-Blackfan anemia 10 (Definitive), mode of inheritance: AD
• Diamond-Blackfan anemia 10 (Strong), mode of inheritance: AD
• Diamond-Blackfan anemia (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diamond-Blackfan anemia 10	AD	Hematologic; Oncologic	Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management	Craniofacial;Hematologic; Musculoskeletal; Oncologic	16317735; 20116044; 20301769; 24942156

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RPS26 gene.

• Diamond-Blackfan anemia 10 (86 variants)
• not provided (15 variants)
• Diamond-Blackfan anemia (14 variants)
• not specified (10 variants)
• Diamond-Blackfan anemia 15 with mandibulofacial dysostosis (2 variants)
• Pure red-cell aplasia;Anemia (1 variants)
• Bone marrow hypocellularity (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPS26 gene is commonly pathogenic or not.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	17	1	21
missense	1	1	13			15
nonsense	7					7
start loss						0
frameshift	4	2				6
inframe indel						0
splice variant	5	6	7	9		27
non coding			2	18	7	27
Total	17	9	25	44	8

Variants in RPS26

This is a list of pathogenic ClinVar variants found in the RPS26 region.

Position	Type	Phenotype	Significance	ClinVar
12-56041628-G-A			Benign (Jun 29, 2018)
12-56041958-T-G		Diamond-Blackfan anemia 10	Benign (Jan 13, 2018)
12-56042018-G-T		Diamond-Blackfan anemia 10	Uncertain significance (Jan 13, 2018)
12-56042037-T-G		Diamond-Blackfan anemia 10	Uncertain significance (Jan 13, 2018)
12-56042066-C-T			Uncertain significance (Sep 16, 2018)
12-56042087-C-T		Diamond-Blackfan anemia 10	Uncertain significance (Jan 12, 2018)
12-56042132-G-A		Diamond-Blackfan anemia 10 • not specified	Benign/Likely benign (Jan 13, 2018)
12-56042134-C-T		Diamond-Blackfan anemia 10	Likely benign (Jan 12, 2018)
12-56042136-C-G		Diamond-Blackfan anemia 10 • not specified	Benign (Jan 13, 2018)
12-56042136-C-T		Diamond-Blackfan anemia 10	Likely benign (Jan 13, 2018)
12-56042140-C-T		Diamond-Blackfan anemia 10	Likely benign (Jan 12, 2018)
12-56042142-C-T		Diamond-Blackfan anemia 10	Benign (Jan 12, 2018)
12-56042145-C-G		Diamond-Blackfan anemia 10 • not specified	Benign (Nov 03, 2022)
12-56042158-G-T		Diamond-Blackfan anemia 10	Likely benign (Jan 13, 2018)
12-56042164-A-G		Diamond-Blackfan anemia 10 • not specified	Benign/Likely benign (May 04, 2022)
12-56042166-G-C		not specified	Uncertain significance (Dec 08, 2020)
12-56042167-A-C		Bone marrow hypocellularity • See cases	Pathogenic (Dec 21, 2022)
12-56042167-A-G		Diamond-Blackfan anemia 10 • Diamond-Blackfan anemia	Pathogenic (Apr 24, 2023)
12-56042167-A-T		Diamond-Blackfan anemia 10	Pathogenic (Nov 01, 2020)
12-56042168-T-C		Diamond-Blackfan anemia	Pathogenic (Dec 01, 2015)
12-56042168-T-G		Diamond-Blackfan anemia 10	Pathogenic (Oct 05, 2019)
12-56042170-G-A		Diamond-Blackfan anemia 10	Pathogenic (Feb 12, 2010)
12-56042170-G-T		Diamond-Blackfan anemia • Diamond-Blackfan anemia 10	Pathogenic/Likely pathogenic (May 02, 2023)
12-56042171-T-G		Diamond-Blackfan anemia 10	Likely pathogenic (Oct 05, 2021)
12-56042173-A-C		Diamond-Blackfan anemia 10	Uncertain significance (Aug 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RPS26	protein_coding	protein_coding	ENST00000356464	4	2480

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.848	0.149	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.93	25	70.7	0.354	0.00000409	739
Missense in Polyphen		1	10.374	0.096392		163
Synonymous	-1.89	34	22.6	1.51	0.00000106	234
Loss of Function	2.31	0	6.20	0.00	3.37e-7	67

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

• Disease: DISEASE: Diamond-Blackfan anemia 10 (DBA10) [MIM:613309]: 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:20116044, ECO:0000269|PubMed:24942156}. 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;Formation of the ternary complex, and subsequently, the 43S complex;Translation initiation complex formation;Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S;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);Ribosomal scanning and start codon recognition;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 (Consensus)

Intolerance Scores

• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.79

Haploinsufficiency Scores

• pHI: 0.125
• hipred: Y
• hipred_score: 0.756
• ghis: 0.539

Essentials

• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Rps26

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;cytoplasmic translation;translation;translational initiation;SRP-dependent cotranslational protein targeting to membrane;negative regulation of RNA splicing
• Cellular component: nucleoplasm;cytosol;small ribosomal subunit;membrane;cytosolic small ribosomal subunit;polysomal ribosome;extracellular exosome;cytoplasmic side of rough endoplasmic reticulum membrane
• Molecular function: RNA binding;mRNA binding;structural constituent of ribosome;protein binding;cadherin binding