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.

Summary from RefSeq, UniProt

P/LP submissions

P/LP missense

0.76

LOEUF

Mechanism· predicted

Clinical Summary— MKI67

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

17 unique Pathogenic / Likely Pathogenic· 412 VUS of 500 total submissions

💊

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

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 OE0.62 (0.50–0.76)

0≤0.351.4

Missense OE1.12 (1.07–1.16)

0≤0.61.4

Synonymous OE1.15

0≤1.21.6

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

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

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17

VUS412

Likely Benign55

Conflicting1

Pathogenic

412

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	17	0	17
Likely Pathogenic	0	0	0	0	0
VUS	0	411	1	0	412
Likely Benign	0	48	0	7	55
Benign	0	0	0	0	0
Conflicting	—				1
Total	0	459	18	7	485

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

View 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.

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