MRPL3

mitochondrial ribosomal protein L3, the group of Small nucleolar RNA protein coding host genes|Large subunit mitochondrial ribosomal proteins|Mitochondrial ribosomal proteins

Basic information

Region (hg38): 3:131462211-131502983

Previous symbols: [ "RPML3" ]

Links

ENSG00000114686 ∙ NCBI:11222 ∙ OMIM:607118 ∙ HGNC:10379 ∙ Uniprot:P09001 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation defect type 9 (Limited), mode of inheritance: AR
• combined oxidative phosphorylation defect type 9 (Strong), mode of inheritance: AR
• mitochondrial disease (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 9	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	21786366

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MRPL3 gene.

• not provided (78 variants)
• Inborn genetic diseases (12 variants)
• not specified (11 variants)
• Combined oxidative phosphorylation defect type 9 (4 variants)
• Neonatal encephalopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MRPL3 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			1	8	3	12
missense		1	30	4	1	36
nonsense			2			2
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region				3	1	4
non coding			1	18	17	36
Total	1	2	34	30	21

Highest pathogenic variant AF is 0.0000132

Variants in MRPL3

This is a list of pathogenic ClinVar variants found in the MRPL3 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-131462637-G-A			Likely benign (Jan 28, 2019)
3-131462737-T-C			Uncertain significance (Nov 09, 2023)
3-131462749-C-G		not specified	Uncertain significance (Feb 12, 2024)
3-131462751-G-A		not specified	Uncertain significance (Dec 02, 2022)
3-131462761-C-T			Uncertain significance (Oct 14, 2022)
3-131462785-G-A		not specified	Conflicting classifications of pathogenicity (Nov 27, 2023)
3-131462789-T-C			Likely benign (Apr 19, 2018)
3-131462816-T-C			Likely benign (Oct 11, 2023)
3-131462820-G-C		Combined oxidative phosphorylation defect type 9	Likely pathogenic (Dec 27, 2019)
3-131462825-T-C		not specified	Benign (Jan 15, 2024)
3-131462832-T-G			Uncertain significance (Nov 08, 2022)
3-131462839-C-T			Benign/Likely benign (Jan 24, 2024)
3-131462868-T-C		not specified	Uncertain significance (Jun 09, 2022)
3-131468049-CA-C			Benign (Aug 06, 2019)
3-131468063-GA-G			Benign (Aug 06, 2019)
3-131468084-T-C		not specified	Likely benign (Nov 07, 2023)
3-131468099-A-G		not specified	Benign (Jan 23, 2024)
3-131468100-G-A		MRPL3-related disorder	Likely benign (Jan 15, 2024)
3-131468101-C-G		Combined oxidative phosphorylation defect type 9	not provided (-)
3-131468123-A-G		Combined oxidative phosphorylation defect type 9	Uncertain significance (Oct 04, 2022)
3-131468161-C-T			Uncertain significance (Oct 31, 2022)
3-131469414-T-C			Likely benign (Nov 27, 2018)
3-131469474-A-G			Likely benign (Jul 15, 2018)
3-131469533-TAC-T			Benign (Aug 06, 2019)
3-131469533-T-TAC			Likely benign (Aug 15, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MRPL3	protein_coding	protein_coding	ENST00000264995	10	40772

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.30e-12	0.0494	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.160	200	194	1.03	0.00000973	2248
Missense in Polyphen		72	78.899	0.91256		947
Synonymous	-0.963	82	71.6	1.14	0.00000385	671
Loss of Function	0.248	19	20.2	0.940	9.56e-7	239

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000472	0.000470
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.0000548	0.0000544
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000248	0.000246
Middle Eastern	0.0000548	0.0000544
South Asian	0.000168	0.000163
Other	0.000213	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Combined oxidative phosphorylation deficiency 9 (COXPD9) [MIM:614582]: A mitochondrial disease characterized by failure to thrive, poor feeding, hypertrophic cardiomyopathy, hepatomegaly, and psychomotor retardation. Death in infancy has been observed in some cases. {ECO:0000269|PubMed:21786366}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ribosome - Homo sapiens (human);Mitochondrial translation initiation;Translation;Metabolism of proteins;Mitochondrial translation elongation;Mitochondrial translation termination;Mitochondrial translation (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.889
• rvis_EVS: -0.09
• rvis_percentile_EVS: 46.92

Haploinsufficiency Scores

• pHI: 0.160
• hipred: N
• hipred_score: 0.486
• ghis: 0.638

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.815

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mrpl3

Gene ontology

• Biological process: translation;mitochondrial translational elongation;mitochondrial translational termination
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial large ribosomal subunit
• Molecular function: RNA binding;structural constituent of ribosome