KIF14

Chr 1AR

kinesin family member 14

Also known as: MCPH20, MKS12

NCBI Gene: 9928ENSG00000118193UniProt: Q15058

This gene encodes a member of the kinesin-3 superfamily of microtubule motor proteins. These proteins are involved in numerous processes including vesicle transport, chromosome segregation, mitotic spindle formation, and cytokinesis. In human HeLa-S3 and 293T cells, this protein is localized to the cytoplasm during interphase, to the spindle poles and spindle microtubules during mitosis, and to the midbody during cytokinesis. An internal motor domain displays microtubule-dependent ATPase activity, consistent with its function as a microtubule motor protein. Knockdown of this gene results in failed cytokinesis with endoreplication, which results in multinucleated cells. This gene has been identified as a likely oncogene in breast, lung and ovarian cancers, as well as retinoblastomas and gliomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

Primary Disease Associations & Inheritance

?Meckel syndrome 12MIM #616258
AR
Microcephaly 20, primary, autosomal recessiveMIM #617914
AR
539
ClinVar variants
39
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— KIF14
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 228 VUS of 539 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.43LOEUF
pLI 0.000
Z-score 5.63
OE 0.30 (0.22–0.43)
Moderately constrained

More LoF-intolerant than ~75% 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.
0.77Z-score
OE missense 0.92 (0.87–0.98)
762 obs / 824.1 exp
Tolerant

Mild missense constraint

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.0.30 (0.22–0.43)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.87–0.98)
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.0.92
0≤1.21.6
LoF obs/exp: 23 / 76.0Missense obs/exp: 762 / 824.1Syn Z: 1.01

ClinVar Variant Classifications

539 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic24
VUS228
Likely Benign97
Benign16
Conflicting2
15
Pathogenic
24
Likely Pathogenic
228
VUS
97
Likely Benign
16
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
10
0
15
Likely Pathogenic
17
0
7
0
24
VUS
6
211
8
3
228
Likely Benign
1
14
35
47
97
Benign
1
2
12
1
16
Conflicting
—2
Total302277251382

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

View in ClinVar →

Protein Context — Lollipop Plot

KIF14 · protein map & ClinVar variants

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

Gene2Phenotype Curations

KIF14-related severe microcephaly and short stature

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Meckel syndrome 12

MIM #616258

Molecular basis of disorder known

Autosomal recessive

Microcephaly 20, primary, autosomal recessive

MIM #617914

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Validation of the important role and prognostic value of KIF14 in triple-negative breast cancer.
Yuan J et al.·Cancer Biol Ther
2025
KIF14 promotes tumor progression and metastasis and is an independent predictor of poor prognosis in human gastric cancer.
Yang Z et al.·Biochim Biophys Acta Mol Basis Dis
2019
KIF14 in cancer biology: implications for diagnosis and therapy.
Bishoyi AK et al.·Clin Exp Metastasis
2026Review
Prognostic Impact and Functional Annotations of KIF11 and KIF14 Expression in Patients with Colorectal Cancer.
Neska-Długosz I et al.·Int J Mol Sci
2021Cohort
Single Nucleotide Variants in KIF14 Gene May Have Prognostic Value in Breast Cancer.
Krus I et al.·Mol Diagn Ther
2022
Loss-of-function mutations in KIF14 cause severe microcephaly and kidney development defects in humans and zebrafish.
Reilly ML et al.·Hum Mol Genet
2019Functional
KIF14 and E2F3 mRNA expression in human retinoblastoma and its phenotype association.
Madhavan J et al.·Mol Vis
2009
Suppression of KIF14 expression inhibits hepatocellular carcinoma progression and predicts favorable outcome.
Yang T et al.·Cancer Sci
2013
KIF14 messenger RNA expression is independently prognostic for outcome in lung cancer.
Corson TW et al.·Clin Cancer Res
2007
Mutations of KIF14 cause primary microcephaly by impairing cytokinesis.
Moawia A et al.·Ann Neurol
2017
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