MKI67

Chr 10

marker of proliferation Ki-67

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

NCBI Gene: 4288 ENSG00000148773 UniProt: P46013

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.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

Active trials

204

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.000

Z-score 3.52

OE 0.62 (0.50–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.68Z-score

OE missense 1.12 (1.07–1.16)

1839 obs / 1647.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.62 (0.50–0.76)

0≤0.351.4

Missense OE?1.12 (1.07–1.16)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 61 / 98.8Missense obs/exp: 1839 / 1647.1Syn Z: -2.90

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

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

ObesityDiabetes Mellitus, Type 2Endocrine System Diseases

Intestinal Metabolic Reprogramming as a Key Mechanism of Gastric Bypass in Humans

ACTIVE NOT RECRUITING

NCT02710370University of PittsburghStarted 2016-02

Breast Cancer

Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

ACTIVE NOT RECRUITING

NCT02955394Phase PHASE2University of Colorado, DenverStarted 2017-09-21

EnzalutamideFulvestrant

Breast Cancer (Early Breast Cancer)Breast Cancer SurvivorsBreast Cancer Prognostic

Real-life Evaluation of Endopredict® in Early HR+/HER2- Breast Cancer

RECRUITING

NCT07379918Assistance Publique - Hôpitaux de ParisStarted 2026-06-28

Endopredict test

Breast CancerEarly-stage Breast Cancer

Multigene Risk Score Combined With Ki-67 Dynamic Assessment in Stratified Neoadjuvant Endocrine Therapy Treatment With or Without CDK4/6 Inhibitors in HR+/HER2- Breast Cancer

ENROLLING BY INVITATION

NCT06650748Phase PHASE2Peking UniversityStarted 2025-05-01

DalpiciclibLetrozole

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

Primary Invasive Breast CancerEstrogen Receptor Positive TumorHuman Epidermal Growth Factor Receptor 2 Negative Tumor

Reaching for Evidence-baSed Chemotherapy Use in Endocrine Sensitive Breast Cancer

ACTIVE NOT RECRUITING

NCT03503799North Eastern German Society of Gynaecological OncologyStarted 2018-07-17