KIF11

Chr 10AD

kinesin family member 11

Also known as: EG5, HKSP, KNSL1, MCLMR, TRIP5

NCBI Gene: 3832 ENSG00000138160 UniProt: P52732 OMIM: 148760

This protein is a motor protein essential for mitotic spindle dynamics, chromosome positioning, and centrosome separation during cell division. Mutations cause microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability through autosomal dominant inheritance. The gene is highly intolerant to loss-of-function variants, indicating mutations can cause disease through haploinsufficiency or other mechanisms that disrupt normal mitotic processes.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

LOFmechanismADLOEUF 0.121 OMIM phenotype

Clinical Summary— KIF11

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Gene-Disease Validity (ClinGen)

microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint

0.12LOEUF

pLI 1.000

Z-score 6.43

OE 0.04 (0.01–0.12)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint

3.27Z-score

OE missense 0.60 (0.54–0.66)

310 obs / 519.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios

LoF OE0.04 (0.01–0.12)

0≤0.351.4

Missense OE0.60 (0.54–0.66)

0≤0.61.4

Synonymous OE0.94

0≤1.21.6

LoF obs/exp: 2 / 52.1Missense obs/exp: 310 / 519.9Syn Z: 0.62

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveKIF11-related microcephaly with or without chorioretinopathy, lymphedema, and developmental delayLOFAD

0.6065th %ile

GOF

0.6639th %ile

LOF

0.55top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF1 literature citation · LOEUF 0.12

GOFprediction 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.

Literature Evidence

LOFIn addition to point mutations, KIF11 haploinsufficiency due to a deletion is causally associated with autosomal dominant microcephaly, chorioretinopathy and mild intellectual disability.PMID:31428438

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.