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

ENSG00000101752NCBI:57534OMIM:608677HGNC:21086Uniprot:Q86YT6AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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
  • neurodevelopmental disorder (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Left ventricular noncompaction 7ADCardiovascularLeft 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 treatmentCardiovascular23314057

ClinVar

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

  • Inborn_genetic_diseases (368 variants)
  • not_provided (208 variants)
  • not_specified (45 variants)
  • Left_ventricular_noncompaction_7 (40 variants)
  • MIB1-related_disorder (23 variants)
  • Primary_familial_hypertrophic_cardiomyopathy (2 variants)
  • Primary_dilated_cardiomyopathy (1 variants)
  • Autism_spectrum_disorder (1 variants)
  • Paroxysmal_atrial_fibrillation (1 variants)
  • See_cases (1 variants)

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. These statistics are base on transcript: NM_000020774.4. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
176
clinvar
179
missense
2
clinvar
254
clinvar
3
clinvar
259
nonsense
8
clinvar
21
clinvar
1
clinvar
30
start loss
0
frameshift
12
clinvar
27
clinvar
39
splice donor/acceptor (+/-2bp)
4
clinvar
9
clinvar
13
Total 0 26 314 180 0

Highest pathogenic variant AF is 0.000100376

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
MIB1protein_codingprotein_codingENST00000261537 21166001
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
3.36e-884.41e-2212533904091257480.00163
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.213435560.6170.00002856612
Missense in Polyphen87167.280.52011899
Synonymous-0.4131991921.040.000009491921
Loss of Function-5.8110557.51.830.00000350615

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.003470.00344
Ashkenazi Jewish0.001930.00189
East Asian0.001430.00141
Finnish0.001390.00139
European (Non-Finnish)0.001580.00156
Middle Eastern0.001430.00141
South Asian0.001880.00186
Other0.001980.00196

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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