MIB1

MIB E3 ubiquitin protein ligase 1, the group of Zinc fingers ZZ-type|Ankyrin repeat domain containing|MicroRNA protein coding host genes|Ring finger proteins

Basic information

Region (hg38): 18:21704957-21870953

Links

ENSG00000101752 ∙ NCBI:57534 ∙ OMIM:608677 ∙ HGNC:21086 ∙ Uniprot:Q86YT6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated cleft palate (No Known Disease Relationship), mode of inheritance: Unknown
• left ventricular noncompaction (Supportive), mode of inheritance: AD
• left ventricular noncompaction 7 (Limited), mode of inheritance: Unknown
• dilated cardiomyopathy (No Known Disease Relationship), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Left ventricular noncompaction 7	AD	Cardiovascular	Left ventricular noncompaction may manifest as depressed systolic function, with potential complications including arrhythmias, systemic embolism, heart failure and sudden death, and surveillance (eg, with echocardiogram and electrocardiogram) may allow early diagnosis and treatment	Cardiovascular	23314057

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MIB1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MIB1 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				132		132
missense		1	138	2		141
nonsense		4	17	1		22
start loss						0
frameshift		10	13			23
inframe indel						0
splice donor/acceptor (+/-2bp)		2	6			8
splice region			5	8		13
non coding			4	44	28	76
Total	0	17	178	179	28

Variants in MIB1

This is a list of pathogenic ClinVar variants found in the MIB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-21740996-G-A			Likely benign (Jul 07, 2018)
18-21741159-G-A			Benign (Jun 19, 2018)
18-21741286-G-A			Benign (Jun 18, 2018)
18-21741303-C-T			Likely benign (Oct 14, 2019)
18-21741527-C-CCGGCGGCAG		not specified	Likely benign (Jun 12, 2017)
18-21741535-AGCGGCGGCGGCGGCG-A		not specified	Likely benign (Feb 22, 2018)
18-21741538-G-A		not specified	Benign (Sep 08, 2017)
18-21741567-C-T		not specified	Benign/Likely benign (-)
18-21741579-C-T			Uncertain significance (Jul 19, 2023)
18-21741587-A-G			Uncertain significance (Jan 22, 2020)
18-21741592-C-T			Likely benign (Dec 31, 2019)
18-21741595-C-T		Inborn genetic diseases	Likely benign (Jan 11, 2022)
18-21741596-C-A		Inborn genetic diseases	Likely benign (Oct 22, 2024)
18-21741597-G-A		Inborn genetic diseases	Uncertain significance (Jun 02, 2022)
18-21741619-AG-A			Uncertain significance (May 27, 2022)
18-21741620-G-C		not specified	Uncertain significance (Apr 21, 2015)
18-21741622-G-A		Inborn genetic diseases	Likely benign (Jun 04, 2019)
18-21741623-G-A		Inborn genetic diseases	Uncertain significance (Aug 24, 2022)
18-21741625-T-C		Inborn genetic diseases	Likely benign (Oct 22, 2024)
18-21741628-C-G		Inborn genetic diseases	Likely benign (Oct 22, 2024)
18-21741629-G-T		Inborn genetic diseases	Uncertain significance (May 02, 2024)
18-21741631-T-C		Inborn genetic diseases	Likely benign (Oct 21, 2024)
18-21741634-G-C		Inborn genetic diseases	Likely benign (Oct 21, 2024)
18-21741643-C-T		Inborn genetic diseases • MIB1-related disorder	Likely benign (Mar 03, 2020)
18-21741648-C-T		Inborn genetic diseases	Uncertain significance (May 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MIB1	protein_coding	protein_coding	ENST00000261537	21	166001

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.36e-88	4.41e-22	125339	0	409	125748	0.00163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.21	343	556	0.617	0.0000285	6612
Missense in Polyphen		87	167.28	0.5201		1899
Synonymous	-0.413	199	192	1.04	0.00000949	1921
Loss of Function	-5.81	105	57.5	1.83	0.00000350	615

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00347	0.00344
Ashkenazi Jewish	0.00193	0.00189
East Asian	0.00143	0.00141
Finnish	0.00139	0.00139
European (Non-Finnish)	0.00158	0.00156
Middle Eastern	0.00143	0.00141
South Asian	0.00188	0.00186
Other	0.00198	0.00196

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF- induced apoptosis (By similarity). Involved in ubiquitination of centriolar satellite CEP131, CEP290 and PCM1 proteins and hence inhibits primary cilium formation in proliferating cells. Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation. {ECO:0000250, ECO:0000269|PubMed:24121310}.
• Disease: DISEASE: Left ventricular non-compaction 7 (LVNC7) [MIM:615092]: A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC7 is an autosomal dominant condition. {ECO:0000269|PubMed:23314057}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: NOTCH-Ncore;Disease;Signal Transduction;Signaling by NOTCH1;Signaling by NOTCH2;NOTCH3 Activation and Transmission of Signal to the Nucleus;Signaling by NOTCH3;Signaling by NOTCH;NOTCH2 Activation and Transmission of Signal to the Nucleus;Notch signaling pathway;Constitutive Signaling by NOTCH1 HD Domain Mutants;Signaling by NOTCH1 HD Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Diseases of signal transduction;Activated NOTCH1 Transmits Signal to the Nucleus (Consensus)

Recessive Scores

• pRec: 0.290

Intolerance Scores

• loftool: 0.882
• rvis_EVS: -1.42
• rvis_percentile_EVS: 4.1

Haploinsufficiency Scores

• pHI: 0.497
• hipred: Y
• hipred_score: 0.675
• ghis: 0.700

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.960

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mib1
• Phenotype: 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); normal 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); hematopoietic system phenotype; embryo phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: mib1
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: dead

Gene ontology

• Biological process: blood vessel development;in utero embryonic development;somitogenesis;neural tube formation;heart looping;endocytosis;Notch signaling pathway;protein ubiquitination;negative regulation of neuron differentiation;positive regulation of endocytosis
• Cellular component: cytoplasm;centrosome;cytosol;plasma membrane;postsynaptic density;cytoplasmic vesicle
• Molecular function: ubiquitin-protein transferase activity;protein binding;zinc ion binding