KIF5C

Chr 2

kinesin family member 5C

Also known as: CDCBM2, KINN, NKHC, NKHC-2, NKHC2

NCBI Gene: 3800ENSG00000168280UniProt: O60282

The protein encoded by this gene is a kinesin heavy chain subunit involved in the transport of cargo within the central nervous system. The encoded protein, which acts as a tetramer by associating with another heavy chain and two light chains, interacts with protein kinase CK2. Mutations in this gene have been associated with complex cortical dysplasia with other brain malformations-2. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Jul 2015]

Primary Disease Associations & Inheritance

UniProtCortical dysplasia, complex, with other brain malformations 2
192
ClinVar variants
7
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— KIF5C
🧬
Gene-Disease Validity (ClinGen)
complex cortical dysplasia with other brain malformations 2 · ADModerate

Moderate evidence — consider for supplementary testing

⚡
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
7 Pathogenic / Likely Pathogenic· 91 VUS of 192 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.12LOEUF
pLI 1.000
Z-score 6.54
OE 0.04 (0.01–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
4.05Z-score
OE missense 0.50 (0.45–0.55)
253 obs / 510.8 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.0.04 (0.01–0.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.50 (0.45–0.55)
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.0.96
0≤1.21.6
LoF obs/exp: 2 / 53.7Missense obs/exp: 253 / 510.8Syn Z: 0.43

ClinVar Variant Classifications

192 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic6
VUS91
Likely Benign50
Benign41
Conflicting3
1
Pathogenic
6
Likely Pathogenic
91
VUS
50
Likely Benign
41
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
0
0
1
Likely Pathogenic
1
4
1
0
6
VUS
4
77
10
0
91
Likely Benign
0
6
25
19
50
Benign
0
1
33
7
41
Conflicting
—3
Total5896926192

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

View in ClinVar →

Protein Context — Lollipop Plot

KIF5C · protein map & ClinVar variants

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

Gene2Phenotype Curations

KIF5C-related cortical dysplasia, complex, with other brain malformations

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
KIF5C deficiency causes abnormal cortical neuronal migration, dendritic branching, and spine morphology in mice.
Li W et al.·Pediatr Res
2022
Expanding the Molecular and Clinical Phenotype of Patients With De Novo Variants in KIF5C: A Six Patient Case Series.
Gracie S et al.·Am J Med Genet A
2025Case report
Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders.
Jurgens JA et al.·Genet Med
2025
Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly.
Poirier K et al.·Nat Genet
2013
Involvement of the kinesin family members KIF4A and KIF5C in intellectual disability and synaptic function.
Willemsen MH et al.·J Med Genet
2014
Abnormal course of the corticospinal tracts in KIF5C-related encephalopathy.
Naim A et al.·Eur J Med Genet
2022
Reduced miR-203 predicts metastasis and poor survival in esophageal carcinoma.
He R et al.·Aging (Albany NY)
2019
A kinesin-1 variant reveals motor-induced microtubule damage in cells.
Budaitis BG et al.·Curr Biol
2022
The importance of routine genetic testing in pediatric epilepsy surgery.
Becker LL et al.·Epilepsia Open
2024
Phenotype description in KIF5C gene hot-spot mutations responsible for malformations of cortical development (MCD).
Duquesne S et al.·Eur J Med Genet
2020Case report
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