KIF2A

Chr 5AD

kinesin family member 2A

Also known as: CDCBM3, HK2, KIF2

NCBI Gene: 3796ENSG00000068796UniProt: O00139

The protein encoded by this gene is a plus end-directed motor required for normal mitotic progression. The encoded protein is required for normal spindle activity during mitosis and is necessary for normal brain development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

Primary Disease Associations & Inheritance

Cortical dysplasia, complex, with other brain malformations 3MIM #615411
AD
570
ClinVar variants
13
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— KIF2A
⚡
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.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 211 VUS of 570 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.16LOEUF
pLI 1.000
Z-score 5.48
OE 0.05 (0.02–0.16)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.04Z-score
OE missense 0.40 (0.35–0.46)
144 obs / 359.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.40 (0.35–0.46)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.82
0≤1.21.6
LoF obs/exp: 2 / 38.8Missense obs/exp: 144 / 359.3Syn Z: 1.54

ClinVar Variant Classifications

570 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic4
VUS211
Likely Benign276
Benign59
Conflicting11
9
Pathogenic
4
Likely Pathogenic
211
VUS
276
Likely Benign
59
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
7
0
9
Likely Pathogenic
0
3
1
0
4
VUS
6
160
39
6
211
Likely Benign
2
23
157
94
276
Benign
0
9
46
4
59
Conflicting
—11
Total8197250104570

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

View 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.

Gene2Phenotype Curations

KIF2A-related malformations of cortical development and microcephaly

strong
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cortical dysplasia, complex, with other brain malformations 3

MIM #615411

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Prognostic significance of KIF2A and KIF20A expression in human cancer: A systematic review and meta-analysis.
Li X et al.·Medicine (Baltimore)
2019Meta-analysis
A class I PI3K signalling network regulates primary cilia disassembly in normal physiology and disease.
Conduit SE et al.·Nat Commun
2024
KIF2A overexpression and its association with clinicopathologic characteristics and unfavorable prognosis in colorectal cancer.
Fan X et al.·Tumour Biol
2015
KIF2A Overexpression and Its Association with Clinicopathologic Characteristics and Poor Prognoses in Patients with Gastric Cancer.
Zhang S et al.·Dis Markers
2016Cohort
Expression of KIF2A, NDC80, CDK1, and CCNB1 in breast cancer patients: Their interaction and linkage with tumor features and prognosis.
Wang C et al.·J Clin Lab Anal
2022Cohort
High KIF2A expression predicts unfavorable prognosis in diffuse large B cell lymphoma.
Zhang Y et al.·Ann Hematol
2017
Aberrant Kif2a and Ki67 expression predicts poor survival in laryngeal squamous cell carcinoma.
Zhang Q et al.·Auris Nasus Larynx
2016
Identification of Kinesin Family Member 2A (KIF2A) as a Promising Therapeutic Target for Osteosarcoma.
Wang ZX et al.·Biomed Res Int
2020
The clinical value of kinesin superfamily protein 2A in hepatocellular carcinoma.
Liu W et al.·Clin Res Hepatol Gastroenterol
2021
Ras transformation uncouples the kinesin-coordinated cellular nutrient response.
Zaganjor E et al.·Proc Natl Acad Sci U S A
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools