MRPS7

Chr 17AR

mitochondrial ribosomal protein S7

Also known as: COXPD34, MRP-S, MRP-S7, RP-S7, RPMS7, S7mt, bMRP27a, uS7m

NCBI Gene: 51081 ENSG00000125445 UniProt: Q9Y2R9

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. In the prokaryotic ribosome, the comparable protein is thought to play an essential role in organizing the 3' domain of the 16 S rRNA in the vicinity of the P- and A-sites. Pseudogenes corresponding to this gene are found on chromosomes 8p and 12p. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Combined oxidative phosphorylation deficiency 34MIM #617872

Active trials

Pathogenic / LP

157

ClinVar variants

Pubs (1 yr)

-0.1

Missense Z

1.12

LOEUF

Clinical Summary— MRPS7

🧬

Gene-Disease Validity (ClinGen)

mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

13 Pathogenic / Likely Pathogenic· 73 VUS of 157 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.12LOEUF

pLI 0.001

Z-score 1.30

OE 0.57 (0.31–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

-0.08Z-score

OE missense 1.02 (0.89–1.17)

150 obs / 147.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.57 (0.31–1.12)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.89–1.17)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.31

0≤1.21.6

LoF obs/exp: 6 / 10.5Missense obs/exp: 150 / 147.3Syn Z: -1.78

0.7228th %ile

GOF

0.4776th %ile

LOF

0.3066th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.