KIF5C

Chr 2AD

kinesin family member 5C

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

NCBI Gene: 3800ENSG00000168280UniProt: O60282OMIM: 604593

KIF5C encodes a kinesin heavy chain that transports cargo along microtubules in the central nervous system and is involved in synaptic transmission, dendritic mRNA trafficking, and axonal transport. Mutations cause complex cortical dysplasia with other brain malformations through autosomal dominant inheritance. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0), reflecting its critical role in neuronal function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.121 OMIM phenotype
Clinical Summary— KIF5C
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Gene-Disease Validity (ClinGen)
complex cortical dysplasia with other brain malformations 2 · ADModerate

Moderate evidence — consider for supplementary testing

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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.
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ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 107 VUS of 314 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
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
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
LoF OE0.04 (0.01–0.12)
0≤0.351.4
Missense OE0.50 (0.45–0.55)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 2 / 53.7Missense obs/exp: 253 / 510.8Syn Z: 0.43
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongKIF5C-related cortical dysplasia, complex, with other brain malformationsOTHERAD
DN
0.5870th %ile
GOF
0.4481th %ile
LOF
0.70top 10%

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

LOFprediction above median · LOEUF 0.12

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

314 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic9
VUS107
Likely Benign110
Benign66
Conflicting4
10
Pathogenic
9
Likely Pathogenic
107
VUS
110
Likely Benign
66
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
9
0
10
Likely Pathogenic
2
7
0
0
9
VUS
7
89
9
2
107
Likely Benign
0
13
67
30
110
Benign
0
1
55
10
66
Conflicting
—4
Total911114042306

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients