KIF2A

Chr 5AD

kinesin family member 2A

Also known as: CDCBM3, HK2, KIF2

The protein is a plus end-directed motor required for normal mitotic spindle activity and brain development. Autosomal dominant loss-of-function mutations cause cortical dysplasia with complex brain malformations. The high constraint against loss-of-function variants (pLI 0.99, LOEUF 0.16) reflects the protein's essential role in mitotic progression and neurodevelopment.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismADLOEUF 0.161 OMIM phenotype
Clinical SummaryKIF2A
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 5.48
OE 0.05 (0.020.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
4.04Z-score
OE missense 0.40 (0.350.46)
144 obs / 359.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.05 (0.020.16)
00.351.4
Missense OE0.40 (0.350.46)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 2 / 38.8Missense obs/exp: 144 / 359.3Syn Z: 1.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongKIF2A-related malformations of cortical development and microcephalyDNAD
DN
0.4784th %ile
GOF
0.4579th %ile
LOF
0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.16

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KIF2A · 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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