MRPS14

Chr 1AR

mitochondrial ribosomal protein S14

Also known as: COXPD38, DJ262D12.2, HSMRPS14, MRP-S14, S14mt, uS14m

NCBI Gene: 63931 ENSG00000120333 UniProt: O60783 OMIM: 611978

This protein is a component of the mitochondrial ribosome's 28S subunit that is essential for mitochondrial protein synthesis. Mutations cause combined oxidative phosphorylation deficiency 38, which follows an autosomal recessive inheritance pattern. The gene is highly constrained against loss-of-function mutations (pLI = 0.0002), indicating that biallelic mutations are likely required for disease manifestation.

OMIM ResearchSummary from RefSeq, OMIM

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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.661 OMIM phenotype

Clinical Summary— MRPS14

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 45 VUS of 67 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.66LOEUF

pLI 0.000

Z-score 0.28

OE 0.88 (0.48–1.66)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.89 (0.74–1.08)

78 obs / 87.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.88 (0.48–1.66)

0≤0.351.4

Missense OE?0.89 (0.74–1.08)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 6 / 6.8Missense obs/exp: 78 / 87.2Syn Z: 0.68

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic1

VUS45

Likely Benign15

Benign1

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	2	0	2
Likely Pathogenic	0	1	0	0	1
VUS	2	41	2	0	45
Likely Benign	0	2	2	11	15
Benign	0	0	0	1	1
Conflicting	—				1
Total	2	44	6	12	65

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

30 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap MRPS14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →