YME1L1

Chr 10AR

YME1 like 1 ATPase

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

NCBI Gene: 10730 ENSG00000136758 UniProt: Q96TA2 OMIM: 607472

YME1L1 encodes an ATP-dependent metalloprotease that degrades mitochondrial proteins and regulates mitochondrial morphology by cleaving OPA1, which is essential for maintaining normal mitochondrial structure and respiratory function. Mutations cause optic atrophy 11, inherited in an autosomal recessive pattern. The gene shows significant constraint against loss-of-function variants (LOEUF 0.448), indicating that complete loss of function is likely pathogenic.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.451 OMIM phenotype

Clinical Summary— YME1L1

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

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ClinVar Variants

50 VUS of 99 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.27 (0.17–0.45)

0≤0.351.4

Missense OE?0.65 (0.59–0.72)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 11 / 40.7Missense obs/exp: 275 / 419.9Syn Z: 0.39

This gene — mechanism propensity

0.78top 25%

GOF

0.6053th %ile

LOF

0.3746th %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

99 submitted variants in ClinVar

ClinVar

Classification Summary

VUS50

Likely Benign26

Conflicting1

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	44	4	2	50
Likely Benign	0	2	7	17	26
Benign	0	0	0	0	0
Conflicting	—				1
Total	0	46	11	19	77

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

View in ClinVar →

0 pathogenic / likely-pathogenic (of 1) ClinVar copy-number / structural variants overlap YME1L1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →