LYRM7

Chr 5AR

LYR motif containing 7

Also known as: C5orf31, MC3DN8, MZM1L

NCBI Gene: 90624ENSG00000186687UniProt: Q5U5X0

Inner mitochondrial membrane complex III (CIII) is the main enzyme complex in the mitochondrial respiratory chain, and Rieske Fe-S protein (UQCRFS1) is the last catalytic subunit added to the complex. The protein encoded by this gene is a nuclear-encoded mitochondrial matrix protein that stabilizes UQCRFS1 and chaperones it to the CIII complex. Defects in this gene are a cause of mitochondrial complex III deficiency, nuclear type 8. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

Primary Disease Associations & Inheritance

Mitochondrial complex III deficiency, nuclear type 8MIM #615838
AR
122
ClinVar variants
31
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— LYRM7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 34 VUS of 122 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.
1.44LOEUF
pLI 0.022
Z-score 0.91
OE 0.57 (0.26–1.44)
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.
0.74Z-score
OE missense 0.68 (0.51–0.93)
29 obs / 42.5 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.0.57 (0.26–1.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.51–0.93)
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.1.01
0≤1.21.6
LoF obs/exp: 3 / 5.3Missense obs/exp: 29 / 42.5Syn Z: -0.04

ClinVar Variant Classifications

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic7
VUS34
Likely Benign30
Benign15
24
Pathogenic
7
Likely Pathogenic
34
VUS
30
Likely Benign
15
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
19
0
24
Likely Pathogenic
3
2
2
0
7
VUS
0
25
8
1
34
Likely Benign
0
2
25
3
30
Benign
0
0
14
1
15
Total730685110

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial complex III deficiency, nuclear type 8

MIM #615838

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Novel Presentation and Variable Phenotypic Spectrum of Homozygous Start-Loss Variant in LYRM7-Associated Mitochondrial Complex III Deficiency.
Luke ND et al.·Am J Med Genet A
2025Case report
LYRM7 mutations cause a multifocal cavitating leukoencephalopathy with distinct MRI appearance.
Dallabona C et al.·Brain
2016Case report
LYRM7 - associated complex III deficiency: A clinical, molecular genetic, MR tomographic, and biochemical study.
Hempel M et al.·Mitochondrion
2017Case report
LYRM7-associated mitochondrial complex III deficiency with non-cavitating leukoencephalopathy and stroke-like episodes.
Alfattal R et al.·Am J Med Genet A
2023Case report
Genotypic Spectrum and Natural History of Cavitating Leukoencephalopathies in Childhood.
Zhang J et al.·Pediatr Neurol
2019Natural history
Severe respiratory complex III defect prevents liver adaptation to prolonged fasting.
Kremer LS et al.·J Hepatol
2016
Multifocal cavitating leukodystrophy-A distinct image in mitochondrial LYRM7 mutations.
Cherian A et al.·Mult Scler Relat Disord
2021Case report
A comprehensive cuproptosis score and associated gene signatures reveal prognostic and immunological features of idiopathic pulmonary fibrosis.
Jing C et al.·Front Immunol
2023
Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction.
Peruzzo R et al.·Nat Commun
2021
Phenotypic variation of TTC19-deficient mitochondrial complex III deficiency: a case report and literature review.
Mordaunt DA et al.·Am J Med Genet A
2015Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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