MRPL49

protein-coding

mitochondrial ribosomal protein L49, the group of Large subunit mitochondrial ribosomal proteins|Mitochondrial ribosomal proteins

Gene summary

Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. Pseudogenes corresponding to this gene are found on chromosomes 5q and 8p. [provided by RefSeq, May 2011]

Previous symbols:

C11orf4

MANE transcript

NM_004927.4

Inheritance

ClinVar variants

P:7U:32B:1

Top phenotype

mitochondrial disease

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr11:65,122,183-65,127,371

External References & Databases

Ensembl (ENSG00000149792)

Transcript & Mutation Effects

hg38 • Region Span ~5.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MRPL49 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 30

Combined oxidative phosphorylation deficiency 60Total: 6

Perrault syndrome 1Total: 4

Mitochondrial diseaseTotal: 2

Combined oxidative phosphorylation defect type 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004927.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense	1 clinvar	2 clinvar	31 clinvar	1 clinvar		35
nonsense	1 clinvar	1 clinvar				2
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	4	3	32	1	0	40

Highest pathogenic variant AF is 0.00006009727

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004927.4	RefSeq	NP_004918.1	4	MANE Select
ENST00000279242.7	Ensembl	ENSP00000279242.2	4	MANE Select
ENST00000526171.5	Ensembl	ENSP00000437177.1	3	Standard
ENST00000526171.6	Ensembl	ENSP00000437177.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mitochondrial translation initiation
Translation
Metabolism of proteins
Mitochondrial translation elongation
Mitochondrial translation termination

Biological Process

mitochondrial translational elongation
mitochondrial translational termination

Molecular Function

structural constituent of ribosome
protein binding

Cellular Component

mitochondrion
mitochondrial inner membrane
mitochondrial ribosome
mitochondrial large ribosomal subunit

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000279242
Coding exons: 4
Length: 5189
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125747
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.282	94	102	0.921	0.00000588	1060
Missense (PolyPhen)		30	32.882	0.91235		362
Synonymous	-0.896	48	40.7	1.18	0.00000220	348
Loss of Function	0.596	6	7.80	0.770	4.32e-7	76

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00024	0.00024	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.157

Intolerance Scores

LoFtool: 0.657
RVIS EVS: -0.01
RVIS percentile EVS: 53.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.791

Gene Damage Prediction

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