KIFC2

Chr 8

kinesin family member C2

NCBI Gene: 90990ENSG00000167702UniProt: Q96AC6

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
57
P/LP submissions
0%
P/LP missense
0.83
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— KIFC2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 204 VUS of 303 total submissions
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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 OE0.59 (0.43–0.83)
0≤0.351.4
Missense OE1.19 (1.10–1.27)
0≤0.61.4
Synonymous OE1.65
0≤1.21.6
LoF obs/exp: 24 / 40.6Missense obs/exp: 540 / 455.5Syn Z: -7.23
DN
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.

ClinVar Variant Classifications

303 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic5
VUS204
Likely Benign21
Benign6
51
Pathogenic
5
Likely Pathogenic
204
VUS
21
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
51
0
51
Likely Pathogenic
0
0
5
0
5
VUS
2
173
29
0
204
Likely Benign
0
12
2
7
21
Benign
0
0
5
1
6
Total2185928287

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

View in ClinVar →

Protein Context — Lollipop Plot

KIFC2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Establishment of a Novel Combined Nomogram for Predicting the Risk of Progression Related to Castration Resistance in Patients With Prostate Cancer
Li S et al.·Front Genet
2022Cohort
The kinesin-14 family motor protein KIFC2 promotes prostate cancer progression by regulating p65.
Liu X et al.·J Biol Chem
2025
The eQTL colocalization and transcriptome-wide association study identify potentially causal genes responsible for economic traits in Simmental beef cattle
Cai W et al.·J Anim Sci Biotechnol
2023
KNTC1 and MCM2 are the molecular targets of gallbladder cancer
Jia W et al.·Aging (Albany NY)
2023
Identification of KIFC3 as a Colorectal Cancer Biomarker and Its Regulatory Mechanism in the Immune Microenvironment Based on Integrated Analysis of Multi-Omics Databases.
Wang F et al.·Biomedicines
2025Functional
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 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