MRPS14

protein-coding

mitochondrial ribosomal protein S14, the group of Small 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 28S subunit protein that belongs to the ribosomal protein S14P family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

MANE transcript

NM_022100.3

Inheritance

ClinVar variants

P:1U:43B:16

Top phenotype

Combined oxidative phosphorylation deficiency 38

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr1:175,010,789-175,023,425

External References & Databases

Ensembl (ENSG00000120333)

Transcript & Mutation Effects

hg38 • Region Span ~12.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: ClinGen

The relationship between *MRPS14* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of June 17, 2024. The *MRPS14* gene encodes the mitochondrial ribosomal subunit S14, a component of the small subunit of the mitochondrial ribosome. The first and only report of *MRPS14* in relation to autosomal recessive primary mitochondrial disease was in 2019 (PMID: 30358850). *MRPS14* has been associated with a single disease entity to date; combined oxidative phosphorylation deficiency 38 [OMIM#618378]. This is one disease entity according to the ClinGen Lumping and Splitting Framework, and is considered a primary mitochondrial disease. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included one homozygous missense variant identified in one case from one publication (PMID: 30358850). Clinical features in this case included hypertrophic cardiomyopathy, Wolff-Parkinson-White arrhythmia, growth restriction, and intellectual disability. It was noted that the clinical phenotype stabilized at age two years, and development and cardiomyopathy improved. Serum lactate was elevated. Complex IV deficiency was noted in skeletal muscle and skin fibroblasts. The mechanism of disease is loss of function. This gene-disease relationship is also supported by a biochemical function shared with other genes associated with primary mitochondrial disease (PMID: 33340416). In summary, there is limited evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on June 17, 2024 (SOP Version 10).

combined oxidative phosphorylation deficiency 38MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032712

Submitter: PanelApp Australia

combined oxidative phosphorylation deficiency 38LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0032712

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Combined oxidative phosphorylation deficiency 38AR

Manifestation: Biochemical; Cardiovascular; Craniofacial; Neurologic

Intervention: Cardiovascular

Rationale: The condition has been described as including features such as hypertrophic cardiomyopathy and arrhythmia, and awareness may allow prompt management of these features

Refs: 30358850

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MRPS14 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 39

not specifiedTotal: 29

MRPS14-related disorderTotal: 4

Combined oxidative phosphorylation deficiency 38Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022100.3. 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				13 clinvar		13
missense		1 clinvar	40 clinvar	3 clinvar		44
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	1	43	16	0	60

Highest pathogenic variant AF is 0.0000012392035

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022100.3	RefSeq	NP_071383.1	3	MANE Select
ENST00000476371.1	Ensembl	ENSP00000420714.1	3	MANE Select
ENST00000367677.3	Ensembl	ENSP00000431220.1	2	Standard
ENST00000881843.1	Ensembl	ENSP00000551902.1	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

translation
mitochondrial translational elongation
mitochondrial translational termination

Molecular Function

RNA binding
structural constituent of ribosome

Cellular Component

mitochondrial inner membrane
mitochondrial ribosome
mitochondrial small ribosomal subunit

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000476371
Coding exons: 3
Length: 12637
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125746
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.349	78	87.2	0.895	0.00000595	817
Missense (PolyPhen)		26	40.168	0.64728		354
Synonymous	0.684	25	29.7	0.841	0.00000172	266
Loss of Function	0.279	6	6.78	0.884	4.49e-7	67

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0	0.0	absent
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.424
RVIS EVS: -0.23
RVIS percentile EVS: 36.86

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.940

Gene Damage Prediction

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