MRPS35

Chr 12

mitochondrial ribosomal protein S35

Also known as: HDCMD11P, MDS023, MRP-S28, MRPS28, mS35

The protein is a component of the mitochondrial ribosome's small 28S subunit and functions in mitochondrial protein synthesis. Mutations cause autosomal recessive mitochondrial disorders affecting multiple organ systems. This gene is highly constrained against loss-of-function variation, indicating that such mutations are likely pathogenic.

Summary from RefSeq
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Primary Disease Associations & Inheritance

UniProtCombined oxidative phosphorylation deficiency 47
0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.25
LOEUF
DN
Mechanism· predicted
Clinical SummaryMRPS35
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.25LOEUF
pLI 0.000
Z-score 0.74
OE 0.81 (0.541.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.30Z-score
OE missense 1.07 (0.941.21)
180 obs / 168.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.81 (0.541.25)
00.351.4
Missense OE1.07 (0.941.21)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 15 / 18.4Missense obs/exp: 180 / 168.9Syn Z: -0.07
DN
0.6162th %ile
GOF
0.4184th %ile
LOF
0.3843th %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

MRPS35 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →