KIF4A

Chr XXLR

kinesin family member 4A

Also known as: KIF4, KIF4G1, MRX100, TMDI, XLID100

NCBI Gene: 24137ENSG00000090889UniProt: O95239

This gene encodes a member of the kinesin 4 subfamily of kinesin related proteins. The encoded protein is an ATP dependent microtubule-based motor protein that is involved in the intracellular transport of membranous organelles. This protein also associates with condensed chromosome arms and may be involved in maintaining chromosome integrity during mitosis. This protein may also be involved in the organization of the central spindle prior to cytokinesis. A pseudogene of this gene is found on chromosome X.[provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 100MIM #300923
XLR
Taurodontism, microdontia, and dens invaginatusMIM #313490
XLR
467
ClinVar variants
65
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— KIF4A
⚡
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
65 Pathogenic / Likely Pathogenic· 194 VUS of 467 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.20LOEUF
pLI 1.000
Z-score 6.08
OE 0.10 (0.05–0.20)
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.
2.56Z-score
OE missense 0.66 (0.60–0.73)
300 obs / 453.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.10 (0.05–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.60–0.73)
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.0.93
0≤1.21.6
LoF obs/exp: 5 / 52.5Missense obs/exp: 300 / 453.3Syn Z: 0.74

ClinVar Variant Classifications

467 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic4
VUS194
Likely Benign24
Benign14
Conflicting3
61
Pathogenic
4
Likely Pathogenic
194
VUS
24
Likely Benign
14
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
4
56
0
61
Likely Pathogenic
0
1
3
0
4
VUS
1
177
16
0
194
Likely Benign
0
6
8
10
24
Benign
0
3
4
7
14
Conflicting
—3
Total21918717300

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

View in ClinVar →

Protein Context — Lollipop Plot

KIF4A · protein map & ClinVar variants

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

Gene2Phenotype Curations

KIF4A-related intellectual disability

limited
Monoallelic X HemizygousLoss 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

Intellectual developmental disorder, X-linked 100

MIM #300923

Molecular basis of disorder known

X-linked recessive

Taurodontism, microdontia, and dens invaginatus

MIM #313490

Molecular basis of disorder known

X-linked recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
KIF4A in disease pathogenesis and therapeutics: from molecular mechanisms to clinical translation.
Liu Y et al.·Biol Direct
2025Review
Expanding the KIF4A-associated phenotype.
Kalantari S et al.·Am J Med Genet A
2021
Molecular mechanism of condensin I activation by KIF4A.
Cutts EE et al.·EMBO J
2025Functional
KIF4A functions as a diagnostic and prognostic biomarker and regulates tumor immune microenvironment in skin cutaneous melanoma.
Zeng S et al.·Pathol Res Pract
2024
X-Linked Bilateral Polymicrogyria With Epilepsy and Intellectual Disability Associated With a Novel KIF4A Variant.
Laflamme N et al.·Am J Med Genet A
2025
Prognostic Value and Immune-Infiltration Pattern of KIF4A in Patients with Endometrial Carcinoma.
Yang Z et al.·Dis Markers
2022Cohort
Bioinformatic and Experimental Analyses Reveal That KIF4A Is a Biomarker of Therapeutic Sensitivity and Predicts Prognosis in Cervical Cancer Patients.
Wu J et al.·Curr Med Sci
2022Cohort
KIF4A Promotes Glioblastoma Malignant Progression and Transmission of Temozolomide Resistance in the Tumor Microenvironment via the HIF1A/VEGFA Axis.
Shen X et al.·CNS Neurosci Ther
2025
[Analysis of a child with X-linked intellectual disability type 100 due to variant of KIF4A gene and a literature review].
Fan X et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025Review
KIF4A: A potential biomarker for prediction and prognostic of prostate cancer.
Chen J et al.·Clin Invest Med
2020
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