MRPL47

Chr 3

mitochondrial ribosomal protein L47

Also known as: CGI-204, L47mt, MRP-L47, NCM1, uL29m

NCBI Gene: 57129 ENSG00000136522 UniProt: Q9HD33 OMIM: 611852

The protein is a component of the mitochondrial ribosome's large 39S subunit and functions in mitochondrial protein synthesis. Mutations cause autosomal recessive mitochondrial disease affecting multiple organ systems. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance patterns.

OMIM ResearchSummary from RefSeq

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. This gene is immediately adjacent to the gene for BAF complex 53 kDa subunit protein a (BAF53a), in a tail-to-tail orientation. Two transcript variants encoding different protein isoforms have been identified. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.89

Clinical Summary— MRPL47

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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

39 VUS of 48 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 1.88

OE 0.49 (0.29–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.22Z-score

OE missense 1.06 (0.92–1.22)

137 obs / 129.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.49 (0.29–0.89)

0≤0.351.4

Missense OE?1.06 (0.92–1.22)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 8 / 16.2Missense obs/exp: 137 / 129.8Syn Z: -0.12

This gene — mechanism propensity

0.6453th %ile

GOF

0.4874th %ile

LOF

0.3162th %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.

ClinVar Variant Classifications

48 submitted variants in ClinVar

ClinVar

Classification Summary

VUS39

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	39	39
Likely Benign	1	1
Benign	0	0
Total	40	40

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap MRPL47 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →