MKI67

Chr 10

marker of proliferation Ki-67

Also known as: KIA, MIB-, MIB-1, PPP1R105

The MKI67 protein acts as a chromosome scaffold during cell division, maintaining proper chromosome separation and clustering through electrostatic charge barriers and RNA-dependent phase separation. This gene is extremely tolerant to loss-of-function variants (LOEUF 0.764), and while MKI67 is widely used as a proliferation marker in cancer research, specific constitutional mutations causing pediatric neurogenetic disorders have not been well-established in the clinical literature. MKI67-related phenotypes would likely involve fundamental cell division abnormalities affecting multiple organ systems including the developing nervous system.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.76
Clinical SummaryMKI67
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.000
Z-score 3.52
OE 0.62 (0.500.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.68Z-score
OE missense 1.12 (1.071.16)
1839 obs / 1647.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.62 (0.500.76)
00.351.4
Missense OE1.12 (1.071.16)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 61 / 98.8Missense obs/exp: 1839 / 1647.1Syn Z: -2.90
DN
0.6453th %ile
GOF
0.2895th %ile
LOF
0.4726th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MKI67 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage IIA Breast Cancer AJCC v8Anatomic Stage IIB Breast Cancer AJCC v8

Ribociclib, Tucatinib, and Trastuzumab for the Treatment of HER2 Positive Breast Cancer

RECRUITING
NCT05319873Phase PHASE1, PHASE2Jonsson Comprehensive Cancer CenterStarted 2022-04-07
CarboplatinDocetaxelFulvestrant
Hormone Receptor Positive HER-2 Negative Breast Cancer

Impact of Endocrine Therapy, Menstrual Cycle, PAM50, Ki67 on Treatment Decisions in HR+ and HER2- Breast Cancer

RECRUITING
NCT05878314University Hospital TuebingenStarted 2023-04-25
Breast Cancer

Trial of Perioperative Endocrine Therapy - Individualising Care

ACTIVE NOT RECRUITING
NCT02338310Phase PHASE3Institute of Cancer Research, United KingdomStarted 2008-09
Aromatase Inhibitors
Anatomic Stage I Breast Cancer AJCC v8Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage III Breast Cancer AJCC v8

Effect of HSD3B1 (1245C) Gene Mutation on Treatment of Stage I-III Breast Cancer

RECRUITING
NCT05183828Phase PHASE4University of WashingtonStarted 2022-01-23
Biospecimen CollectionLetrozoleQuestionnaire Administration
Breast Cancer

Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer

ACTIVE NOT RECRUITING
NCT00616967Phase PHASE2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsStarted 2008-05
carboplatinpaclitaxel albumin-stabilized nanoparticle formulationvorinostat
Psoriasis VulgarisPsoriasisSkin Diseases

Residual Disease MEMory in PSOriasis Skin During EnstiLAR® and Narrow-band Ultraviolet B Therapy: The MEMPSOLAR Study

ACTIVE NOT RECRUITING
NCT05185258Phase PHASE4Aarhus University HospitalStarted 2022-02-16
EnstilarPlacebo-vehicle
Cervix Uteri SILHPVCIN2

Regression of Cervical Precancerous Lesions and Associated Risk Factors

RECRUITING
NCT06147388General University Hospital, PragueStarted 2022-09-01
Colposcopy
High Grade GliomaGlioblastoma

A Phase 0/1 Study of BDTX-1535 in Recurrent High-Grade Glioma (rHGG) and Newly Diagnosed Glioblastoma (nGBM) Participants With EGFR Alterations or Fusions

RECRUITING
NCT06072586Phase EARLY_PHASE1St. Joseph's Hospital and Medical Center, PhoenixStarted 2023-10-18
BDTX-1535BDTX-1535 combined with radiation therapyBDTX-1535 combined with temozolomide and radiation therapy
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
Cancer

A Nutrition & Exercise Prehabilitation Intervention on Inflammatory Biomarkers in AI Cancer Patients

RECRUITING
NCT06644560Phase NAUniversity of ArizonaStarted 2025-11-13
Prehabilitation Intervention
Bladder Cancer

Clinical Trail of Neoadjuvant of Tislelizumab Combined With Palbociclib in Patients With Platinum-refractory Bladder Urothelial Carcinoma

RECRUITING
NCT06364956Phase PHASE1, PHASE2Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityStarted 2024-05-15
Tislelizumab combined with two predefined dose groups of palbociclibRP2D dose Of Tislelizumab combined with palbociclib was selected for phase II clinical trial.
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
Clinical Literature
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