MRPL49

Chr 11AR

mitochondrial ribosomal protein L49

Also known as: C11orf4, COXPD60, L49mt, MRP-L49, NOF, NOF1, mL49

NCBI Gene: 740ENSG00000149792UniProt: Q13405

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. Pseudogenes corresponding to this gene are found on chromosomes 5q and 8p. [provided by RefSeq, May 2011]

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 60MIM #621195
AR
45
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MRPL49
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 31 VUS of 45 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.
1.50LOEUF
pLI 0.000
Z-score 0.60
OE 0.77 (0.42–1.50)
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.
0.28Z-score
OE missense 0.92 (0.78–1.09)
94 obs / 102.0 exp
Tolerant

Mild missense constraint

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.0.77 (0.42–1.50)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.78–1.09)
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.1.18
0≤1.21.6
LoF obs/exp: 6 / 7.8Missense obs/exp: 94 / 102.0Syn Z: -0.90

ClinVar Variant Classifications

45 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic4
VUS31
Likely Benign1
9
Pathogenic
4
Likely Pathogenic
31
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
7
0
9
Likely Pathogenic
0
2
2
0
4
VUS
0
29
2
0
31
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total13311045

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

View in ClinVar →

Protein Context — Lollipop Plot

MRPL49 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Combined oxidative phosphorylation deficiency 60

MIM #621195

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MRPL49
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools