MIB2

protein-coding

MIB E3 ubiquitin protein ligase 2, the group of Ankyrin repeat domain containing|Ring finger proteins|Zinc fingers ZZ-type

Gene summary

The protein encoded by this gene is an E3 ubiquitin protein ligase that mediates ubiquitination of proteins in the Notch signaling pathway. The encoded protein may be a suppressor of melanoma invasion. [provided by RefSeq, Mar 2017]

Previous symbols:

ZZANK1

MANE transcript

NM_001170687.4

Inheritance

—

ClinVar variants

U:217B:37

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr1:1,615,454-1,630,605

External References & Databases

Ensembl (ENSG00000197530)

Transcript & Mutation Effects

hg38 • Region Span ~15.2 kb

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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 MIB2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 219

not providedTotal: 24

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001170687.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	17 clinvar	6 clinvar	25
missense			207 clinvar	13 clinvar	1 clinvar	221
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	217	30	7	254

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 359 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001170687.4	RefSeq	NP_001164158.3	18	MANE Select
ENST00000355826.10	Ensembl	ENSP00000348081.6	18	MANE Select
NM_001170686.4	RefSeq	NP_001164157.3	18	Standard
NM_001170688.2	RefSeq	NP_001164159.2	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NOTCH-Ncore
Disease
Signal Transduction
Immune System
Adaptive Immune System

Biological Process

protein polyubiquitination
Notch signaling pathway
protein ubiquitination
positive regulation of I-kappaB kinase/NF-kappaB signaling

Molecular Function

actin binding
ubiquitin-protein transferase activity
protein binding
zinc ion binding
ubiquitin protein ligase activity

Cellular Component

ubiquitin ligase complex
cytoplasm
early endosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000505820
Coding exons: 20
Length: 15196
Individuals with no LoFs: 124036
Homozygous LoFs: 7
Heterozygous LoFs: 574
Defined: 124617
p: 0.00233

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.623	644	690	0.933	0.0000494	6664
Missense (PolyPhen)		196	269.45	0.72741		2660
Synonymous	-3.36	395	319	1.24	0.0000251	2280
Loss of Function	3.59	19	45.0	0.422	0.00000237	476

Population LoF Frequency

Population	CAF	p-value	Status
African	0.030	0.028	notable
Latino/Admixed American	0.0018	0.0017	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00042	0.00039	rare
Finnish	0.0017	0.0015	notable
European (Non-Finnish)	0.00033	0.00028	rare
South Asian	0.00041	0.00039	rare
Other	0.00087	0.00083	rare

dbNSFP Gene Annotations

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. {ECO:0000250|UniProtKB:Q8R516}.;

Recessive Scores

pRec: 0.129

Intolerance Scores

LoFtool: 0.153
RVIS EVS: -0.03
RVIS percentile EVS: 50.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.991

Gene Damage Prediction

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