YME1L1

YME1 like 1 ATPase, the group of AAA ATPases

Basic information

Region (hg38): 10:27110088-27155266

Links

ENSG00000136758

∙ NCBI:10730 ∙ OMIM:607472 ∙ HGNC:12843 ∙ Uniprot:Q96TA2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal recessive optic atrophy (Supportive), mode of inheritance: AR
optic atrophy 11 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Optic atrophy 11	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Biochemical; Neurologic; Ophthalmologic	27495975

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the YME1L1 gene.

not_provided (150 variants)
not_specified (64 variants)
Optic_atrophy_11 (4 variants)
YME1L1-related_disorder (3 variants)
Retinal_dystrophy (2 variants)
3-Methylglutaconic_aciduria (1 variants)
Long_QT_syndrome (1 variants)
Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YME1L1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014263.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	34 clinvar	2 clinvar	37
missense	1 clinvar	1 clinvar	93 clinvar	5 clinvar	1 clinvar	101
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	1	94	39	3

Highest pathogenic variant AF is 0.0000027393733

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YME1L1	protein_coding	protein_coding	ENST00000326799	20	44813

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0290	0.971	125735	0	11	125746	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.51	275	420	0.655	0.0000220	5060
Missense in Polyphen		67	162.04	0.41347		1911
Synonymous	0.390	134	140	0.958	0.00000718	1476
Loss of Function	4.31	11	40.7	0.271	0.00000211	508

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000441	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.0000665	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: ATP-dependent metalloprotease that catalyzes the degradation of folded and unfolded proteins with a suitable degron sequence in the mitochondrial intermembrane region (PubMed:26923599, PubMed:27786171). Plays an important role in regulating mitochondrial morphology and function by cleaving OPA1 at position S2, giving rise to a form of OPA1 that promotes maintenance of normal mitochondrial structure and mitochondrial protein metabolism (PubMed:18076378, PubMed:26923599, PubMed:27495975). Ensures cell proliferation, maintains normal cristae morphology and complex I respiration activity, promotes antiapoptotic activity and protects mitochondria from the accumulation of oxidatively damaged membrane proteins (PubMed:22262461). Required for normal, constitutive degradation of PRELID1 (PubMed:27495975). Catalyzes the degradation of OMA1 in response to membrane depolarization (PubMed:26923599). Required to control the accumulation of nonassembled respiratory chain subunits (NDUFB6, OX4 and ND1) (PubMed:22262461). {ECO:0000269|PubMed:18076378, ECO:0000269|PubMed:22262461, ECO:0000269|PubMed:26923599, ECO:0000269|PubMed:27495975, ECO:0000269|PubMed:27786171}.;
Disease: DISEASE: Optic atrophy 11 (OPA11) [MIM:617302]: An autosomal recessive disease characterized by progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA11 patients also manifest delayed psychomotor development, intellectual disability, ataxia, and leukoencephalopathy on brain imaging. {ECO:0000269|PubMed:27495975}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.319

Intolerance Scores

loftool: 0.0738
rvis_EVS: -0.82
rvis_percentile_EVS: 11.88

Haploinsufficiency Scores

pHI: 0.202
hipred: Y
hipred_score: 0.532
ghis: 0.670

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.984

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Yme1l1
Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Gene ontology

Biological process: proteolysis;protein quality control for misfolded or incompletely synthesized proteins;mitochondrion organization;cell population proliferation;protein hexamerization;mitochondrial protein processing;mitochondrial protein catabolic process;negative regulation of apoptotic process
Cellular component: mitochondrion;mitochondrial inner membrane;membrane;integral component of membrane;nuclear body
Molecular function: ATP-dependent peptidase activity;metalloendopeptidase activity;protein binding;ATP binding;metal ion binding