MRPL21

protein-coding

mitochondrial ribosomal protein L21, 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. This gene encodes a 39S subunit protein. Multiple transcript variants encoding different isoforms were identified through sequence analysis although some may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

MANE transcript

NM_181514.2

Inheritance

—

ClinVar variants

U:36B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.37

Max pathogenic AF

—

Genomic locus

chr11:68,891,276-68,903,835

External References & Databases

Ensembl (ENSG00000197345)

Transcript & Mutation Effects

hg38 • Region Span ~12.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MRPL21 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 31

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181514.2. 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			2 clinvar			2
missense			31 clinvar	2 clinvar		33
nonsense						0
start loss					1 clinvar	1
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	36	2	1	39

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181514.2	RefSeq	NP_852615.1	7	MANE Select
ENST00000362034.7	Ensembl	ENSP00000354580.2	7	MANE Select
NM_181515.2	RefSeq	NP_852616.1	4	Standard
ENST00000450904.6	Ensembl	ENSP00000389400.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ribosome - Homo sapiens (human)
Mitochondrial translation initiation
Translation
Metabolism of proteins
Mitochondrial translation elongation

Biological Process

mitochondrial translational elongation
mitochondrial translational termination

Molecular Function

RNA binding
structural constituent of ribosome

Cellular Component

mitochondrion
mitochondrial inner membrane
mitochondrial large ribosomal subunit

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000362034
Coding exons: 7
Length: 12560
Individuals with no LoFs: 125688
Homozygous LoFs: 0
Heterozygous LoFs: 60
Defined: 125748
p: 0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.270	108	116	0.929	0.00000650	1295
Missense (PolyPhen)		26	33.844	0.76824		406
Synonymous	-0.836	55	47.7	1.15	0.00000276	423
Loss of Function	-1.25	18	13.1	1.37	7.49e-7	135

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.0011	0.0011	notable
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00032	0.00029	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.250
RVIS EVS: 0.95
RVIS percentile EVS: 90.01

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.390

Gene Damage Prediction

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