MIB1

Chr 18AD

MIB E3 ubiquitin protein ligase 1

Also known as: DIP-1, DIP1, LVNC7, MIB, ZZANK2, ZZZ6

NCBI Gene: 57534 ENSG00000101752 UniProt: Q86YT6 OMIM: 608677

The MIB1 protein functions as an E3 ubiquitin ligase that positively regulates Notch signaling by ubiquitinating Notch receptors to facilitate their endocytosis, and is also involved in regulating apoptosis and primary cilium formation. Mutations cause left ventricular noncompaction, a cardiomyopathy characterized by prominent trabeculations and deep intertrabecular recesses in the left ventricle. This condition follows autosomal dominant inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein containing multiple ankyrin repeats and RING finger domains that functions as an E3 ubiquitin ligase. The encoded protein positively regulates Notch signaling by ubiquitinating the Notch receptors, thereby facilitating their endocytosis. This protein may also promote the ubiquitination and degradation of death-associated protein kinase 1 (DAPK1). [provided by RefSeq, Jun 2013]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Left ventricular noncompaction 7MIM #615092

Clinical highlights

Gene-disease validity (ClinGen)

dilated cardiomyopathy · ADLimitednot for standalone diagnostic reporting

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.97

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

1.97LOEUF

pLI 0.000

Z-score -5.81

OE 1.83 (1.54–1.97)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

3.21Z-score

OE missense 0.62 (0.56–0.67)

343 obs / 556.1 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?1.83 (1.54–1.97)

0≤0.351.4

Missense OE?0.62 (0.56–0.67)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 105 / 57.5Missense obs/exp: 343 / 556.1Syn Z: -0.41

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MIB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Diffuse Large B Cell Lymphoma

Mixed Molecular Clinical Index (MMCI) in Diffuse Large B-cell Lymphoma (DLBCL)

RECRUITING

NCT04300101Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSStarted 2020-05-14

Prospective cohortRetrospective cohort

Multiple Myeloma

A Clinical Study of TQB2029 for Injection in Subjects With Multiple Myeloma

RECRUITING

NCT06700395Phase PHASE1Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.Started 2024-11-28

TQB2029 injection

Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell TypeRefractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type

Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

ACTIVE NOT RECRUITING

NCT02443077Phase PHASE3National Cancer Institute (NCI)Started 2016-10-12

Autologous Bone Marrow TransplantationAutologous Hematopoietic Stem Cell TransplantationCarmustine

Breast Cancer

CONcurrent vs SEqueNTial Adjuvant Treatments in Early Breast Cancer

ACTIVE NOT RECRUITING

NCT02918084Phase PHASE3IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, ItalyStarted 2013-06

Anastrozole or Letrozole or ExemestaneAnastrozole or Letrozole or Exemestane

Breast NeoplasmBreast CancerBreast Tumors

Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy

RECRUITING

NCT05582499Phase PHASE2Fudan UniversityStarted 2022-11-01

DalpiciclibPyrotinibSHR-A1811

Inflammatory Bowel Diseases

Regulation of Mucosal Healing in Inflammatory Bowel Disease

RECRUITING

NCT04504136Phase NATerrence A BarrettStarted 2021-04-30

Serial Biopsy

Breast Cancer

QL1706 Plus Neoadjuvant Endocrine Therapy in HR-Positive/HER2-Negative Breast Cancer With a Poor Response to Neoadjuvant Chemotherapy

NOT YET RECRUITING

NCT07782840Phase PHASE2Hebei Medical University Fourth HospitalStarted 2026-10-01

Iparomlimab and Tuvonralimab (QL1706)Aromatase Inhibitor (AI)CDK4/6 inhibitor

Cervix Uteri SILHPVCIN2

Regression of Cervical Precancerous Lesions and Associated Risk Factors

RECRUITING

NCT06147388General University Hospital, PragueStarted 2022-09-01

Colposcopy

Breast Cancer

NeoadjuVAnt muLti-agENT Chemotherapy or Patritumab Deruxtecan With or Without endocrINE Therapy for High-risk HR+/HER2- Breast Cancer - VALENTINE Trial

ACTIVE NOT RECRUITING

NCT05569811Phase PHASE2SOLTI Breast Cancer Research GroupStarted 2022-11-25

Patritumab deruxtecanChemotherapyLetrozole

Breast Cancer Lung Metastasis

Evaluation of a Genetic Risk Score for Lung Metastasis and Prognosis in Breast Cancer

NOT YET RECRUITING

NCT07752966Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityStarted 2026-10-01

Standard management

High-Risk CancerLocally Advanced Breast Cancer

Three Fraction Radiation to Induce Immuno-Oncologic Response

ACTIVE NOT RECRUITING

NCT03978663Phase NALondon Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sStarted 2020-09-02