MKI67

Chr 10

marker of proliferation Ki-67

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

Enables RNA binding activity and molecular condensate scaffold activity. Involved in chromosome segregation and regulation of mitotic nuclear division. Located in chromosome; nucleolus; and nucleoplasm. Is active in condensed chromosome. Implicated in several diseases, including Crohn's disease; colorectal cancer; endocrine gland cancer (multiple); graft-versus-host disease; and human immunodeficiency virus infectious disease. Biomarker of several diseases, including Barrett's esophagus; autoimmune disease of musculoskeletal system (multiple); endocrine gland cancer (multiple); gastrointestinal system cancer (multiple); and lung cancer (multiple). [provided by Alliance of Genome Resources, Jul 2025]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 0.76
Clinical SummaryMKI67
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
389 VUS of 493 total submissions
💊
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 OE?0.62 (0.500.76)
00.351.4
Missense OE?1.12 (1.071.16)
00.61.4
Synonymous OE?1.15
01.21.6
LoF obs/exp: 61 / 98.8Missense obs/exp: 1839 / 1647.1Syn Z: -2.90

This gene — mechanism propensity

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

493 submitted variants in ClinVar

Classification Summary

VUS389
Likely Benign59
Benign25
Conflicting5
389
VUS
59
Likely Benign
25
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
1
388
0
0
389
Likely Benign
0
49
0
10
59
Benign
0
13
0
12
25
Conflicting
5
Total1450022478

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

View in ClinVar →

86 pathogenic / likely-pathogenic (of 92) ClinVar copy-number / structural variants overlap MKI67 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

MKI67 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Glioblastoma WHO Grade IV

Phase 0 With Expansion Phase Clinical Trial of Quisinostat Plus Radiotherapy in Newly-diagnosed and Recurrent Grade 4 IDH-Wildtype Glioblastomas

ACTIVE NOT RECRUITING
NCT06824662Phase EARLY_PHASE1Nader SanaiStarted 2025-09-04
Quisinostat
Breast CancerHER2-negative Breast CancerHormone Receptor Positive Tumor

Elacestrant With/Without Triptorelin in Premenopausal Women With Luminal Breast Cancer

RECRUITING
NCT05982093Phase PHASE2SOLTI Breast Cancer Research GroupStarted 2023-02-03
ElacestrantTriptorelinTamoxifen 20 mg
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
Neoadjuvant radiotherapy
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.
Breast Cancer

Trial of Perioperative Endocrine Therapy - Individualising Care

ACTIVE NOT RECRUITING
NCT02338310Phase PHASE3Institute of Cancer Research, United KingdomStarted 2008-09
Aromatase Inhibitors
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
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
Type1diabetes

Crosstalk Between Mucosal-Associated Invariant T (MAIT) Cells and the Gut Microbiota and Mucosa in the Development of Type 1 Diabetes in Children

RECRUITING
NCT05054361Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2022-01-01
MAIT cells analysisMAIT cytokines production analysisLactulose/Mannitol Test
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
Breast Cancer

Fulvestrant or Capecitabine Combined With Pyrotinib in HR+/HER2+ Metastatic Breast Cancer

RECRUITING
NCT04646759Phase PHASE3Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityStarted 2020-10-14
Fulvestrant combined with PyrotinibCapecitabine combined with Pyrotinib
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
HER2-positive Gastric Cancer

Cinrebafusp Alfa in Combination With Ramucirumab and Paclitaxel in HER2-High Gastric or GEJ Adenocarcinoma and in Combination With Tucatinib in HER2-Low Gastric or GEJ Andenocarinoma

ACTIVE NOT RECRUITING
NCT05190445Phase PHASE2Pieris Pharmaceuticals, Inc.Started 2021-11-01
Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxelCinrebafusp alfa (PRS-343) in combination with tucatinib