MUL1

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

Basic information

Region (hg38): 1:20499448-20508151

Previous symbols: [ "C1orf166" ]

Links

ENSG00000090432 ∙ NCBI:79594 ∙ OMIM:612037 ∙ HGNC:25762 ∙ Uniprot:Q969V5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MUL1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MUL1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	2	3
missense			24		1	25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	24	1	3

Variants in MUL1

This is a list of pathogenic ClinVar variants found in the MUL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-20500713-C-G		not specified	Uncertain significance (Oct 12, 2021)
1-20500724-G-A		not specified	Uncertain significance (Feb 07, 2023)
1-20500737-T-C		not specified	Uncertain significance (Feb 14, 2023)
1-20500764-C-T		not specified	Uncertain significance (Apr 07, 2022)
1-20500767-G-A		not specified	Uncertain significance (Dec 09, 2023)
1-20500779-T-C		not specified	Uncertain significance (Feb 14, 2024)
1-20500792-G-A			Likely benign (Jun 05, 2018)
1-20500814-C-T		not specified	Uncertain significance (May 02, 2024)
1-20500922-T-C		not specified	Uncertain significance (Mar 01, 2024)
1-20500944-G-A		not specified	Uncertain significance (Dec 15, 2022)
1-20501045-G-A		not specified	Uncertain significance (Feb 23, 2023)
1-20501048-T-C		not specified	Uncertain significance (Feb 01, 2023)
1-20501048-T-G		not specified	Uncertain significance (May 03, 2023)
1-20501054-C-T		not specified	Uncertain significance (Jun 13, 2022)
1-20501097-G-T		not specified	Uncertain significance (Aug 14, 2023)
1-20501113-C-T			Benign (Dec 31, 2019)
1-20501172-C-T		not specified	Uncertain significance (Jan 18, 2023)
1-20501194-G-A			Benign (Jun 18, 2018)
1-20501264-G-A		not specified	Uncertain significance (Aug 04, 2023)
1-20501340-C-T		not specified	Uncertain significance (May 25, 2022)
1-20501384-T-C		not specified	Uncertain significance (Feb 15, 2023)
1-20502167-T-A		not specified	Uncertain significance (Jan 23, 2024)
1-20503239-G-A		not specified	Uncertain significance (Dec 09, 2023)
1-20503244-G-C		not specified	Uncertain significance (Mar 01, 2023)
1-20503281-T-C		not specified	Uncertain significance (Jan 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MUL1	protein_coding	protein_coding	ENST00000264198	4	8712

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000191	0.698	125692	0	56	125748	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.857	176	211	0.834	0.0000128	2269
Missense in Polyphen		58	72.875	0.79588		816
Synonymous	-1.03	104	91.5	1.14	0.00000552	725
Loss of Function	1.12	11	15.8	0.696	9.11e-7	165

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000936	0.000936
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000162	0.000158
Middle Eastern	0.00	0.00
South Asian	0.000327	0.000327
Other	0.000513	0.000489

dbNSFP

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}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.734
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.61

Haploinsufficiency Scores

• pHI: 0.155
• hipred: Y
• hipred_score: 0.675
• ghis: 0.484

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.872

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mul1

Gene ontology

• 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;regulation of mitochondrion organization;protein ubiquitination;protein sumoylation;negative regulation of cell growth;protein destabilization;positive regulation of protein sumoylation;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of innate immune response;negative regulation of defense response to virus by host;protein stabilization;mitochondrion localization;regulation of mitochondrial membrane potential;negative regulation of protein kinase B signaling;negative regulation of type I interferon-mediated signaling pathway;cellular response to exogenous dsRNA;negative regulation of chemokine (C-C motif) ligand 5 production;positive regulation of mitochondrial fission;regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway;positive regulation of dendrite extension;positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization
• Cellular component: mitochondrion;peroxisome;membrane;axon;integral component of mitochondrial outer membrane;neuronal cell body
• Molecular function: ubiquitin-protein transferase activity;protein binding;SUMO transferase activity;ubiquitin protein ligase binding;identical protein binding;metal ion binding