KLC4

Chr 6AR

kinesin light chain 4

Also known as: CONDRHN, KNSL8, bA387M24.3

NCBI Gene: 89953ENSG00000137171UniProt: Q9NSK0OMIM: 620909

The KLC4 protein is a kinesin light chain that enables kinesin binding and is involved in microtubule-based organelle transport within cells. Mutations cause early-childhood-onset neurodegeneration with retinitis pigmentosa, sensorineural hearing loss, and demyelinating peripheral neuropathy, following autosomal recessive inheritance. This multisystem disorder affects the retina, auditory system, and peripheral nerves in addition to causing central neurodegeneration.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.531 OMIM phenotype
Clinical Summary— KLC4
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 101 VUS of 132 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.001
Z-score 3.75
OE 0.33 (0.21–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.89Z-score
OE missense 0.87 (0.80–0.95)
340 obs / 389.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.21–0.53)
0≤0.351.4
Missense OE0.87 (0.80–0.95)
0≤0.61.4
Synonymous OE0.84
0≤1.21.6
LoF obs/exp: 12 / 36.5Missense obs/exp: 340 / 389.6Syn Z: 1.54
DN
0.7327th %ile
GOF
0.5759th %ile
LOF
0.4037th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

132 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS101
Benign1
10
Pathogenic
1
Likely Pathogenic
101
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
9
0
10
Likely Pathogenic
1
0
0
0
1
VUS
0
98
3
0
101
Likely Benign
0
0
0
0
0
Benign
0
0
1
0
1
Total298130113

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

View in ClinVar →

Protein Context — Lollipop Plot

KLC4 · 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
A humanized Caenorhabditis elegans model of Hereditary Spastic Paraplegia-associated variants in kinesin light chain KLC4
Gümüşderelioğlu S et al.·bioRxiv
2023Functional
Study of the Lipolysis Effect of Nanoliposome-Encapsulated Ganoderma lucidum Protein Hydrolysates on Adipocyte Cells Using Proteomics Approach
Krobthong S et al.·Foods
2021
Identification of tumor antigens and immune subtypes in head and neck squamous cell carcinoma for mRNA vaccine development
Chen Y et al.·Front Cell Dev Biol
2022
Proteomic profiling of the prefrontal cortex reveals Dysregulated Mitochondria-Metabolism-Synapse axis in a chronic Stress-Induced mouse model of depression.
Zhang Y et al.·Neurosci Lett
2026Functional
Exome sequence analysis of rare frequency variants in Late-Onset Alzheimer Disease
Sundarrajan S et al.·Metab Brain Dis
2023
Top 5 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