KIF1C

Chr 17AR

kinesin family member 1C

Also known as: LTXS1, SATX2, SAX2, SPAX2, SPG58

NCBI Gene: 10749ENSG00000129250UniProt: O43896

The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. Mutations in this gene are a cause of spastic ataxia 2, autosomal recessive. [provided by RefSeq, May 2014]

Primary Disease Associations & Inheritance

Spastic ataxia 2, autosomal recessiveMIM #611302
AR
573
ClinVar variants
36
Pathogenic / LP
0.72
pLI score
0
Active trials
Clinical Summary— KIF1C
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.72) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 279 VUS of 573 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.
0.34LOEUF
pLI 0.718
Z-score 5.52
OE 0.21 (0.13–0.34)
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.
1.40Z-score
OE missense 0.85 (0.79–0.91)
585 obs / 688.5 exp
Tolerant

Mild missense constraint

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.0.21 (0.13–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.79–0.91)
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.1.10
0≤1.21.6
LoF obs/exp: 12 / 57.0Missense obs/exp: 585 / 688.5Syn Z: -1.29

ClinVar Variant Classifications

573 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic19
VUS279
Likely Benign208
Benign32
Conflicting18
17
Pathogenic
19
Likely Pathogenic
279
VUS
208
Likely Benign
32
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
1
10
0
17
Likely Pathogenic
11
5
3
0
19
VUS
2
249
24
4
279
Likely Benign
0
9
82
117
208
Benign
0
1
25
6
32
Conflicting
—18
Total19265144127573

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

View in ClinVar →

Protein Context — Lollipop Plot

KIF1C · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spastic ataxia 2, autosomal recessive

MIM #611302

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hereditary ataxias and paraparesias: clinical and genetic update.
Parodi L et al.·Curr Opin Neurol
2018Review
Force generation of KIF1C is impaired by pathogenic mutations.
Siddiqui N et al.·Curr Biol
2022
KIF1C and new Huntingtin-interacting protein 1 binding proteins regulate rheumatoid arthritis fibroblast-like synoviocytes' phenotypes.
Laragione T et al.·Front Immunol
2024
Molecular Characterization of Portuguese Patients with Hereditary Cerebellar Ataxia.
Santos M et al.·Cells
2022Cohort
KIF1C-related disorders: spastic ataxia or hypomyelinating leukodystrophy? A paradigm of classification ambiguity.
Benzoni C et al.·Neurogenetics
2025Case report
Clinical phenotype of hereditary spastic paraplegia due to KIF1C gene mutations across life span.
Yücel-Yılmaz D et al.·Brain Dev
2018Case report
Profiling the male germline genome to unravel its reproductive potential.
Cheung S et al.·Fertil Steril
2023
Kif1c regulates osteoclastic bone resorption as a downstream molecule of p130Cas.
Kobayakawa M et al.·Cell Biochem Funct
2020
Overcoming the divide between ataxias and spastic paraplegias: Shared phenotypes, genes, and pathways.
Synofzik M et al.·Mov Disord
2017Review
KIF1C Variants Are Associated with Hypomyelination, Ataxia, Tremor, and Dystonia in Fraternal Twins.
Marchionni E et al.·Tremor Other Hyperkinet Mov (N Y)
2019Case 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