MKI67

Chr 10

marker of proliferation Ki-67

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

NCBI Gene: 4288 ENSG00000148773 UniProt: P46013 OMIM: 176741

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.

OMIM 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; endocrine gland cancer (multiple); gastrointestinal system cancer (multiple); interstitial cystitis; and lung cancer (multiple). [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

220

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in MKI67?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 11

4,253 rare PASS variants

Rare truncating (LoF)

1 in 370

412 rare PASS variants

Rare synonymous (reference)

1 in 32

1,559 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MKI67. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 17	1 in 450
South Asian	~43k	1 in 11	1 in 290
Remaining (unassigned)	~30k	1 in 12	1 in 330
European (Finnish)	~27k	1 in 40	1 in 310
Admixed American	~22k	1 in 13	1 in 370
African / African American	~21k	1 in 10	1 in 400
East Asian	~20k	1 in 13	1 in 290
Ashkenazi Jewish	~13k	1 in 42	1 in 1,600
Middle Eastern	~2,884	1 in 11	1 in 480

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 14 coding exons well covered in gnomAD exomes; exons 4, 5 marginal. Genomes: all 14.? see exons ↓