MRPL40

Chr 22

mitochondrial ribosomal protein L40

Also known as: L40mt, MRP-L22, MRP-L40, NLVCF, URIM, mL40

The protein is a component of the large 39S subunit of mitochondrial ribosomes, which synthesize proteins within mitochondria. Deletions involving this gene may contribute to velo-cardio-facial syndrome and DiGeorge syndrome, which are autosomal dominant disorders affecting cardiac, facial, and immune system development. The gene shows tolerance to loss-of-function variants (pLI 0.05, LOEUF 0.79), suggesting that isolated mutations in this gene alone may not be sufficient to cause disease.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 0.79
Clinical SummaryMRPL40
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.053
Z-score 2.05
OE 0.35 (0.170.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.52Z-score
OE missense 1.14 (0.991.33)
122 obs / 106.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.35 (0.170.79)
00.351.4
Missense OE1.14 (0.991.33)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 4 / 11.5Missense obs/exp: 122 / 106.7Syn Z: -0.80
DN
0.78top 25%
GOF
0.6247th %ile
LOF
0.2871th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MRPL40 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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