KLC2

Chr 11AR

kinesin light chain 2

NCBI Gene: 64837ENSG00000174996UniProt: Q9H0B6

The protein encoded by this gene is a light chain of kinesin, a molecular motor responsible for moving vesicles and organelles along microtubules. Defects in this gene are a cause of spastic paraplegia, optic atrophy, and neuropathy (SPOAN) syndrome. [provided by RefSeq, Mar 2016]

Primary Disease Associations & Inheritance

Spastic paraplegia, optic atrophy, and neuropathyMIM #609541
AR
206
ClinVar variants
13
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— KLC2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 130 VUS of 206 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.
0.32LOEUF
pLI 0.975
Z-score 4.55
OE 0.15 (0.08–0.32)
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.
2.02Z-score
OE missense 0.72 (0.65–0.79)
285 obs / 398.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.15 (0.08–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.65–0.79)
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.0.93
0≤1.21.6
LoF obs/exp: 5 / 33.4Missense obs/exp: 285 / 398.4Syn Z: 0.70

ClinVar Variant Classifications

206 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic2
VUS130
Likely Benign48
Benign14
Conflicting1
11
Pathogenic
2
Likely Pathogenic
130
VUS
48
Likely Benign
14
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
2
0
2
VUS
2
116
11
1
130
Likely Benign
0
4
16
28
48
Benign
0
2
7
5
14
Conflicting
—1
Total21224734206

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

View in ClinVar →

Protein Context — Lollipop Plot

KLC2 · 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 paraplegia, optic atrophy, and neuropathy

MIM #609541

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The kinesin light chain-2, a target of mRNA stabilizing protein HuR, inhibits p53 protein phosphorylation to promote radioresistance in NSCLC.
Qiao S et al.·Thorac Cancer
2023
Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development.
Seese SE et al.·Dev Dyn
2023
Overexpression of KLC2 due to a homozygous deletion in the non-coding region causes SPOAN syndrome.
Melo US et al.·Hum Mol Genet
2015
A Novel SLC5A5 Variant Reveals the Crucial Role of Kinesin Light Chain 2 in Thyroid Hormonogenesis.
Martín M et al.·J Clin Endocrinol Metab
2021Case report
A humanized Caenorhabditis elegans model of hereditary spastic paraplegia-associated variants in KLC4.
Gümüşderelioğlu S et al.·Dis Model Mech
2023Functional
High expression of kinesin light chain-2, a novel target of miR-125b, is associated with poor clinical outcome of elderly non-small-cell lung cancer patients.
Wang M et al.·Br J Cancer
2015Cohort
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