KIFC2

Chr 8

kinesin family member C2

NCBI Gene: 90990 ENSG00000167702 OMIM: 615216

KIFC2 encodes a kinesin motor protein that hydrolyzes ATP to drive microtubule-based transport of synaptic vesicles and neurotransmitter receptor complexes in neurons. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene shows minimal constraint against loss-of-function variants based on population data.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable ATP hydrolysis activity; microtubule binding activity; and plus-end-directed microtubule motor activity. Predicted to be involved in anterograde dendritic transport of neurotransmitter receptor complex; axon guidance; and synaptic vesicle transport. Predicted to be located in cytoskeleton and dendrite cytoplasm. Predicted to be part of kinesin complex. Predicted to be active in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.83

Clinical Summary— KIFC2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.000

Z-score 2.41

OE 0.59 (0.43–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.41Z-score

OE missense 1.19 (1.10–1.27)

540 obs / 455.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.59 (0.43–0.83)

0≤0.351.4

Missense OE?1.19 (1.10–1.27)

0≤0.61.4

Synonymous OE?1.65

0≤1.21.6

LoF obs/exp: 24 / 40.6Missense obs/exp: 540 / 455.5Syn Z: -7.23

This gene — mechanism propensity

0.79top 25%

GOF

0.78top 25%

LOF

0.3163th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.