GeneBe

MUL1

protein-coding

mitochondrial E3 ubiquitin protein ligase 1, the group of Ring finger proteins

Gene summary

Enables several functions, including p53 binding activity; ubiquitin protein ligase binding activity; and ubiquitin-like protein transferase activity. Involved in several processes, including cellular response to exogenous dsRNA; negative regulation of defense response; and regulation of mitochondrion organization. Located in several cellular components, including mitochondrial outer membrane; neuronal cell body; and peroxisome. Part of TOM complex. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:
  • C1orf166

MANE transcript

NM_024544.3

Inheritance

—

ClinVar variants

U:61B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr1:20,499,448-20,508,151

External References & Databases

Ensembl (ENSG00000090432)NCBI Gene (79594)OMIM (612037)HGNC:25762GenCCUniProt (Q969V5)AlphaFoldClinVar (MUL1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~8.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MUL1 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 59
not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024544.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
 3
missense
58
clinvar
1
clinvar
1
clinvar
 60
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total00612366
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_024544.3RefSeqNP_078820.24MANE Select
ENST00000264198.5EnsemblENSP00000264198.34MANE Select
ENST00000908517.1EnsemblENSP00000578576.14Standard
ENST00000908517.2EnsemblENSP00000578576.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Post-translational protein modification
  • Metabolism of proteins
  • Ub-specific processing proteases
  • Deubiquitination

Biological Process

  • mitochondrial fission
  • apoptotic process
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • activation of JUN kinase activity
  • negative regulation of mitochondrial fusion

Molecular Function

  • ubiquitin-protein transferase activity
  • protein binding
  • SUMO transferase activity
  • ubiquitin protein ligase binding
  • identical protein binding

Cellular Component

  • mitochondrion
  • peroxisome
  • membrane
  • axon
  • integral component of mitochondrial outer membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000264198
Coding exons
4
Length
8712
Individuals with no LoFs
125692
Homozygous LoFs
0
Heterozygous LoFs
56
Defined
125748
p
0.000223
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.8571762110.8340.00001282269
Missense (PolyPhen)5872.8750.79588816
Synonymous-1.0310491.51.140.00000552725
Loss of Function1.121115.80.6969.11e-7165

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000690.00061rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.000160.00016rare
South Asian0.000330.00033rare
Other0.000510.00049rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Exhibits weak E3 ubiquitin-protein ligase activity (PubMed:18591963, PubMed:19407830, PubMed:22410793). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (PubMed:18591963, PubMed:19407830, PubMed:22410793). Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to be involved in regulation of Akt signaling by targeting phosphorylated Akt to proteosomal degradation (PubMed:22410793). Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations (PubMed:19407830). Plays a role in the control of mitochondrial morphology by promoting mitochondrial fragmentation, and influences mitochondrial localization (PubMed:19407830, PubMed:18207745, PubMed:18213395). Likely to promote mitochondrial fission through negatively regulating the mitochondrial fusion proteins MFN1 and MFN2, acting in a pathway that is parallel to the PRKN/PINK1 regulatory pathway (PubMed:24898855). May also be involved in the sumoylation of the membrane fission protein DNM1L (PubMed:18207745, PubMed:19407830). Inhibits cell growth (PubMed:18591963, PubMed:22410793). When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis (PubMed:23399697). Involved in the modulation of innate immune defense against viruses by inhibiting DDX58-dependent antiviral response (PubMed:23399697). Can mediate DDX58 sumoylation and disrupt its polyubiquitination (PubMed:23399697). {ECO:0000269|PubMed:18207745, ECO:0000269|PubMed:18213395, ECO:0000269|PubMed:18591963, ECO:0000269|PubMed:19407830, ECO:0000269|PubMed:22410793, ECO:0000269|PubMed:23399697, ECO:0000269|PubMed:24898855}.;

Recessive Scores

pRec
0.122

Intolerance Scores

LoFtool
0.734
RVIS EVS
0.02
RVIS percentile EVS
55.61

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.872

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.