KLC4

Chr 6

kinesin light chain 4

Also known as: CONDRHN, KNSL8, bA387M24.3

NCBI Gene: 89953 ENSG00000137171 UniProt: Q9NSK0

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.

ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable kinesin binding activity. Predicted to be involved in microtubule-based movement. Predicted to be located in microtubule. Predicted to be part of kinesin complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.53

Clinical Summary— KLC4

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

📋

ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 98 VUS of 121 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.33 (0.21–0.53)

0≤0.351.4

Missense OE?0.87 (0.80–0.95)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 12 / 36.5Missense obs/exp: 340 / 389.6Syn Z: 1.54

This gene — mechanism propensity

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

121 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic2

VUS98

Benign1

Pathogenic

Likely Pathogenic

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	1	0	0	1
Likely Pathogenic	2	0	0	2
VUS	0	98	0	98
Likely Benign	0	0	0	0
Benign	0	0	1	1
Total	3	98	1	102

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap KLC4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →