LYRM7

Chr 5AR

LYR motif containing 7

Also known as: C5orf31, MC3DN8, MZM1L

The protein encoded by LYRM7 is a nuclear-encoded mitochondrial matrix protein that stabilizes the Rieske Fe-S protein (UQCRFS1) and chaperones it to mitochondrial respiratory chain complex III. Mutations cause mitochondrial complex III deficiency, nuclear type 8, inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant-negative effects on complex III assembly and function.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 1.441 OMIM phenotype
Clinical SummaryLYRM7
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.02) — 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
1.44LOEUF
pLI 0.022
Z-score 0.91
OE 0.57 (0.261.44)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.74Z-score
OE missense 0.68 (0.510.93)
29 obs / 42.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.261.44)
00.351.4
Missense OE0.68 (0.510.93)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 3 / 5.3Missense obs/exp: 29 / 42.5Syn Z: -0.04
DN
0.76top 25%
GOF
0.7126th %ile
LOF
0.2777th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

LYRM7 · 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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