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

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation defect type 9 (Limited), 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 (76 variants)
• not specified (11 variants)
• Inborn genetic diseases (6 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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	7	3	11
missense		1	25	2	1	29
nonsense			2			2
start loss						0
frameshift	1			1		2
inframe indel		1				1
splice variant	1			4	1	6
non coding			1	16	17	34
Total	2	2	29	30	22

Highest pathogenic variant AF is 0.0000132

Variants in MRPL3

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

Position	Type	Phenotype	Significance	ClinVar
3-131462637-G-A			Likely benign (Jan 28, 2019)
3-131462737-T-C			Uncertain significance (May 27, 2022)
3-131462751-G-A		Inborn genetic diseases	Uncertain significance (Dec 02, 2022)
3-131462785-G-A		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
3-131462789-T-C			Likely benign (Apr 19, 2018)
3-131462816-T-C			Likely benign (Dec 31, 2019)
3-131462820-G-C		Combined oxidative phosphorylation defect type 9	Likely pathogenic (Dec 27, 2019)
3-131462825-T-C		not specified	Benign (Aug 09, 2022)
3-131462832-T-G			Uncertain significance (May 31, 2022)
3-131462839-C-T			Benign/Likely benign (May 01, 2023)
3-131462868-T-C		Inborn genetic diseases	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 (Jul 29, 2022)
3-131468099-A-G		not specified	Benign (Oct 27, 2022)
3-131468100-G-A			Likely benign (Dec 31, 2019)
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)
3-131469684-T-G		not specified	Benign (Oct 30, 2022)
3-131469687-AAC-A			Likely benign (Sep 20, 2022)

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