YME1L1

Chr 10AR

YME1 like 1 ATPase

Also known as: FTSH, MEG4, OPA11, PAMP, YME1L

NCBI Gene: 10730ENSG00000136758UniProt: Q96TA2

The protein encoded by this gene is the human ortholog of yeast mitochondrial AAA metalloprotease, Yme1p. It is localized in the mitochondria and can functionally complement a yme1 disruptant yeast strain. It is proposed that this gene plays a role in mitochondrial protein metabolism and could be involved in mitochondrial pathologies. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

Primary Disease Associations & Inheritance

?Optic atrophy 11MIM #617302
AR
307
ClinVar variants
14
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— YME1L1
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 140 VUS of 307 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.45LOEUF
pLI 0.029
Z-score 4.31
OE 0.27 (0.17–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.51Z-score
OE missense 0.65 (0.59–0.72)
275 obs / 419.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.27 (0.17–0.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.59–0.72)
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.0.96
0≤1.21.6
LoF obs/exp: 11 / 40.7Missense obs/exp: 275 / 419.9Syn Z: 0.39

ClinVar Variant Classifications

307 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic2
VUS140
Likely Benign97
Benign55
Conflicting1
12
Pathogenic
2
Likely Pathogenic
140
VUS
97
Likely Benign
55
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
11
0
12
Likely Pathogenic
0
1
1
0
2
VUS
0
122
15
3
140
Likely Benign
0
4
45
48
97
Benign
0
2
49
4
55
Conflicting
—1
Total013012155307

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

View in ClinVar →

Protein Context — Lollipop Plot

YME1L1 · 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

?Optic atrophy 11

MIM #617302

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SREBP1c-Mediated Transcriptional Repression of YME1L1 Contributes to Acute Kidney Injury by Inducing Mitochondrial Dysfunction in Tubular Epithelial Cells.
Xin W et al.·Adv Sci (Weinh)
2025
CLPB disaggregase dysfunction impacts the functional integrity of the proteolytic SPY complex.
Baker MJ et al.·J Cell Biol
2024Functional
YME1L1 Dysfunction Associated With 3-Methylglutaconic Aciduria.
Demetriadou A et al.·J Inherit Metab Dis
2025Case report
A novel mitochondrial unfolded protein response-related risk signature to predict prognosis, immunotherapy and sorafenib sensitivity in hepatocellular carcinoma.
Zhang S et al.·Apoptosis
2024
Mitochondrial AAA protease gene associated with immune infiltration is a prognostic biomarker in human ovarian cancer.
Liao WT et al.·Pathol Res Pract
2022
Mitochondrial dynamics: Biological roles, molecular machinery, and related diseases.
El-Hattab AW et al.·Mol Genet Metab
2018Review
Brain transcriptomic, metabolic and mitohormesis properties associated with N-propargylglycine treatment: A prevention strategy against neurodegeneration.
Teramayi F et al.·Brain Res
2024
A network model of a cooperative genetic landscape in brain tumors.
Bredel M et al.·JAMA
2009Functional
Functional CRISPR and shRNA Screens Identify Involvement of Mitochondrial Electron Transport in the Activation of Evofosfamide.
Hunter FW et al.·Mol Pharmacol
2019Functional
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