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

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.

Summary from RefSeq, OMIM, UniProt

Research Assistant →

Primary Disease Associations & Inheritance

Left ventricular noncompaction 7MIM #615092

Active trials

Pubs (1 yr)

P/LP submissions

P/LP missense

1.97

LOEUF

LOF

Mechanism· G2P

Clinical Summary— MIB1

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Gene-Disease Validity (ClinGen)

dilated cardiomyopathy · ADLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

13 unique Pathogenic / Likely Pathogenic· 254 VUS of 400 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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 OE1.83 (1.54–1.97)

0≤0.351.4

Missense OE0.62 (0.56–0.67)

0≤0.61.4

Synonymous OE1.04

0≤1.21.6

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

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic11

VUS254

Likely Benign112

Pathogenic

Likely Pathogenic

254

VUS

112

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	2	0	2
Likely Pathogenic	8	0	3	0	11
VUS	22	212	19	1	254
Likely Benign	0	1	2	109	112
Benign	0	0	0	0	0
Total	30	213	26	110	379

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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

Breast CancerBreast Cancer With Low to Intermediate HER2 Expression

Application of Multimodal MRI-based Radiomics in Histological Grading and Prognostic Assessment of Breast Cancer

NOT YET RECRUITING

NCT07389200Hao XuStarted 2028-01-01

DCE-MRI

Hereditary Pulmonary Alveolar Proteinosis

Safety and Efficacy of PMT Therapy of hPAP

RECRUITING

NCT05761899Phase PHASE1, PHASE2Children's Hospital Medical Center, CincinnatiStarted 2023-06-26

Gene-Corrected Macrophages administered by bronchoscopic instillation

Merkel Cell Carcinoma

Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma

RECRUITING

NCT06151236Phase PHASE2Melanoma Institute AustraliaStarted 2024-03-11

Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination

Hormone-Resistant Prostate CancerMetastatic Prostate CarcinomaRecurrent Prostate Carcinoma

Trametinib in Treating Patients With Progressive Metastatic Hormone-Resistant Prostate Cancer

ACTIVE NOT RECRUITING

NCT02881242Phase PHASE2Jonsson Comprehensive Cancer CenterStarted 2018-01-30

Laboratory Biomarker AnalysisQuality-of-Life AssessmentTrametinib

Menopausal Symptoms

Micronized Progesterone Versus Norethisterone Acetate in Combination With Estrogen as Menopausal Hormone Therapy

RECRUITING

NCT05586724Phase PHASE3Angelica Lindén HirschbergStarted 2022-03-15

Micronized progesterone in continuous combination with oral estrogenNorethisterone acetate in continuous combination with oral estrogen

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

BRCA-Mutated Breast CarcinomaHER2-negative Breast Cancer

Neoadjuvant Treatment of gBRCA-Mutated HER2-Negative Breast Cancer With HRS-1167 and Famitinib ± Camrelizumab

RECRUITING

NCT06516289Phase PHASE2Fudan UniversityStarted 2024-09-30

HRS-1167FamitinibCamrelizumab

Prostate Cancer

GU-01: Glycyrrhizin in Prostate Cancer

RECRUITING

NCT06378346Phase PHASE2University of Illinois at ChicagoStarted 2024-07-25