RPL35A

ribosomal protein L35a, the group of L ribosomal proteins

Basic information

Region (hg38): 3:197950190-197956610

Links

ENSG00000182899 ∙ NCBI:6165 ∙ OMIM:180468 ∙ HGNC:10345 ∙ Uniprot:P18077 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Diamond-Blackfan anemia 5 (Strong), mode of inheritance: AD
• Diamond-Blackfan anemia 5 (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 5	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; Oncologic	16317735; 18535205; 20301769; 23812780

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RPL35A gene.

• Diamond-Blackfan anemia 5 (4 variants)
• Diamond-Blackfan anemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPL35A 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	19		21
missense		1	32	2		35
nonsense	1					1
start loss						0
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)		2	1			3
splice region			7	5	1	13
non coding			1	22	5	28
Total	4	3	36	43	5

Variants in RPL35A

This is a list of pathogenic ClinVar variants found in the RPL35A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-197950217-T-G		Diamond-Blackfan anemia 5	Uncertain significance (Jan 12, 2018)
3-197950221-G-A		Diamond-Blackfan anemia 5	Uncertain significance (Jan 12, 2018)
3-197950237-G-C		not specified	Likely benign (Nov 27, 2017)
3-197950795-G-A			Benign (May 20, 2019)
3-197950933-A-G		Diamond-Blackfan anemia 5	Benign (Jan 13, 2018)
3-197950934-A-T		Diamond-Blackfan anemia 5	Uncertain significance (Jun 03, 2022)
3-197950937-C-T		Diamond-Blackfan anemia 5	Uncertain significance (Jan 13, 2018)
3-197950981-A-G		Diamond-Blackfan anemia 5	Uncertain significance (Jun 27, 2023)
3-197950982-C-T		Diamond-Blackfan anemia 5	Uncertain significance (Dec 03, 2022)
3-197950984-C-A		Diamond-Blackfan anemia 5	Uncertain significance (Nov 15, 2022)
3-197950989-T-C		Diamond-Blackfan anemia 5	Likely benign (Apr 13, 2022)
3-197950995-T-C		Diamond-Blackfan anemia 5	Likely benign (Jul 06, 2022)
3-197951141-G-A		Diamond-Blackfan anemia 5	Likely benign (Nov 13, 2023)
3-197951141-G-T		Diamond-Blackfan anemia 5	Likely benign (Jan 11, 2024)
3-197951145-CT-C		Diamond-Blackfan anemia 5	Benign (Feb 16, 2023)
3-197951146-T-A		Diamond-Blackfan anemia 5	Likely benign (Apr 23, 2021)
3-197951152-G-T		Diamond-Blackfan anemia 5	Likely benign (Dec 16, 2019)
3-197951154-C-G		Diamond-Blackfan anemia 5 • Diamond-Blackfan anemia • RPL35A-related disorder	Conflicting classifications of pathogenicity (May 24, 2023)
3-197951154-C-T		Diamond-Blackfan anemia 5	Likely benign (Mar 22, 2023)
3-197951155-T-G		Diamond-Blackfan anemia 5	Likely benign (Mar 29, 2023)
3-197951163-T-C		Diamond-Blackfan anemia 5	Uncertain significance (Feb 01, 2022)
3-197951168-C-T		not specified • Diamond-Blackfan anemia 5 • Diamond-Blackfan anemia • RPL35A-related disorder	Benign/Likely benign (Dec 18, 2023)
3-197951175-A-G		Diamond-Blackfan anemia 5 • RPL35A-related disorder	Uncertain significance (Mar 07, 2023)
3-197951180-T-C		Diamond-Blackfan anemia 5	Likely benign (May 01, 2021)
3-197951181-G-A		Diamond-Blackfan anemia 5	Uncertain significance (Aug 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RPL35A	protein_coding	protein_coding	ENST00000464167	4	6624

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.895	0.104	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.37	33	63.8	0.517	0.00000379	701
Missense in Polyphen		3	7.1376	0.42031		117
Synonymous	-1.86	33	21.9	1.51	0.00000123	223
Loss of Function	2.51	0	7.31	0.00	4.48e-7	75

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: Required for the proliferation and viability of hematopoietic cells. Plays a role in 60S ribosomal subunit formation. The protein was found to bind to both initiator and elongator tRNAs and consequently was assigned to the P site or P and A site. {ECO:0000269|PubMed:18535205}.
• 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 (Consensus)

Recessive Scores

• pRec: 0.212

Intolerance Scores

• rvis_EVS: 0.28
• rvis_percentile_EVS: 70.87

Haploinsufficiency Scores

• pHI: 0.254
• hipred: Y
• hipred_score: 0.783
• ghis: 0.621

Essentials

• essential_gene_CRISPR: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.925

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rpl35a

Zebrafish Information Network

• Gene name: rpl35a
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;cytoplasmic translation;rRNA processing;translation;translational initiation;SRP-dependent cotranslational protein targeting to membrane;ribosomal large subunit biogenesis
• Cellular component: cytosol;membrane;cytosolic large ribosomal subunit;extracellular exosome
• Molecular function: tRNA binding;RNA binding;structural constituent of ribosome;protein binding