KIF2C

Chr 1

kinesin family member 2C

Also known as: CT139, KNSL6, MCAK

The protein is a kinesin-like microtubule motor that depolymerizes microtubules at their plus ends and regulates chromosome segregation during mitosis. Mutations cause autosomal dominant microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR), presenting with primary microcephaly and developmental delays from infancy. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.55
Clinical SummaryKIF2C
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.000
Z-score 3.90
OE 0.36 (0.250.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.39Z-score
OE missense 0.81 (0.740.88)
335 obs / 414.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.250.55)
00.351.4
Missense OE0.81 (0.740.88)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 16 / 43.8Missense obs/exp: 335 / 414.9Syn Z: -0.57
DN
0.77top 25%
GOF
0.5465th %ile
LOF
0.3355th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KIF2C · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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