MRPL44

mitochondrial ribosomal protein L44, the group of Large subunit mitochondrial ribosomal proteins|Mitochondrial ribosomal proteins

Basic information

Region (hg38): 2:223957463-223967714

Links

ENSG00000135900 ∙ NCBI:65080 ∙ OMIM:611849 ∙ HGNC:16650 ∙ Uniprot:Q9H9J2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• infantile hypertrophic cardiomyopathy due to MRPL44 deficiency (Moderate), mode of inheritance: AR
• infantile hypertrophic cardiomyopathy due to MRPL44 deficiency (Strong), mode of inheritance: AR
• infantile hypertrophic cardiomyopathy due to MRPL44 deficiency (Supportive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 16	AR	Cardiovascular	Individuals have been reported as teenagers with hypertrophic cardiomyopathy (as well as with infantile-onset hyptertrophic cardiomyopathy), and surveillance for cardiomyopathy (eg, with echocardiography/electrocardiography) may allow early detection and medical treatment of disease manifestations	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal	23315540

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MRPL44 gene.

• Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MRPL44 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				30	2	32
missense		2	51	4	1	58
nonsense	1		1			2
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	3		4
non coding				11	8	19
Total	1	2	54	45	11

Variants in MRPL44

This is a list of pathogenic ClinVar variants found in the MRPL44 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-223957478-G-A			Likely benign (Nov 23, 2022)
2-223957478-G-T			Likely benign (May 11, 2023)
2-223957491-A-G		Inborn genetic diseases	Uncertain significance (Jun 22, 2023)
2-223957499-G-T			Likely benign (Oct 31, 2022)
2-223957502-G-A		not specified	Likely benign (Nov 18, 2015)
2-223957502-G-C			Uncertain significance (Jul 18, 2022)
2-223957506-G-A		Inborn genetic diseases	Uncertain significance (Mar 09, 2022)
2-223957510-A-G			Uncertain significance (Nov 27, 2023)
2-223957512-C-T		MRPL44-related disorder	Likely benign (Dec 23, 2023)
2-223957519-T-G			Uncertain significance (Jul 05, 2022)
2-223957523-G-A			Likely benign (Oct 13, 2022)
2-223957525-C-A			Uncertain significance (Jan 11, 2022)
2-223957534-C-T			Uncertain significance (Jun 17, 2022)
2-223957550-T-A			Likely benign (Aug 23, 2022)
2-223957564-T-A			Uncertain significance (Feb 28, 2023)
2-223957575-T-G		Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
2-223957581-G-T			Uncertain significance (Aug 17, 2023)
2-223957596-C-G		Inborn genetic diseases	Uncertain significance (May 24, 2024)
2-223957601-G-A			Likely benign (Nov 27, 2023)
2-223957603-A-T			Uncertain significance (May 22, 2022)
2-223957647-C-T			Uncertain significance (Dec 03, 2021)
2-223957649-C-G			Likely benign (Jun 28, 2022)
2-223957660-C-T		not specified • MRPL44-related disorder	Likely benign (Dec 11, 2017)
2-223957857-C-A			Likely benign (Sep 07, 2018)
2-223957952-T-C			Benign (Jun 14, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MRPL44	protein_coding	protein_coding	ENST00000258383	4	10311

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.06e-9	0.0733	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0785	177	180	0.984	0.00000874	2138
Missense in Polyphen		47	57.584	0.81619		611
Synonymous	0.206	68	70.2	0.969	0.00000350	673
Loss of Function	-0.162	13	12.4	1.05	5.21e-7	162

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000284	0.000277
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000109	0.000109
South Asian	0.000459	0.000457
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the 39S subunit of mitochondrial ribosome. May have a function in the assembly/stability of nascent mitochondrial polypeptides exiting the ribosome. {ECO:0000269|PubMed:23315540}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 16 (COXPD16) [MIM:615395]: An autosomal recessive, mitochondrial disorder characterized by hypertrophic cardiomyopathy, liver steatosis, and decreased levels of mitochondrial complexes I and IV in heart and skeletal muscle. {ECO:0000269|PubMed:23315540}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Mitochondrial translation initiation;Translation;Metabolism of proteins;Mitochondrial translation elongation;Mitochondrial translation termination;Mitochondrial translation (Consensus)

Recessive Scores

• pRec: 0.115

Intolerance Scores

• loftool: 0.815
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.6

Haploinsufficiency Scores

• pHI: 0.0944
• hipred: Y
• hipred_score: 0.562
• ghis: 0.643

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.894

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mrpl44

Gene ontology

• Biological process: RNA processing;production of siRNA involved in RNA interference;primary miRNA processing;pre-miRNA processing;mitochondrial translational elongation;mitochondrial translational termination;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: nucleus;mitochondrion;mitochondrial inner membrane;mitochondrial large ribosomal subunit;plasma membrane
• Molecular function: RNA binding;double-stranded RNA binding;ribonuclease III activity;protein binding