KLC2

Chr 11AR

kinesin light chain 2

NCBI Gene: 64837 ENSG00000174996 UniProt: Q9H0B6 OMIM: 611729

The encoded protein is a kinesin light chain that transports vesicles and organelles along microtubules and recruits kinesin-1 to lysosomes for lysosomal transport. Mutations cause spastic paraplegia, optic atrophy, and neuropathy (SPOAN) syndrome, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.32), indicating intolerance to protein loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.321 OMIM phenotype

Clinical Summary— KLC2

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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.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 125 VUS of 211 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.15 (0.08–0.32)

0≤0.351.4

Missense OE?0.72 (0.65–0.79)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 5 / 33.4Missense obs/exp: 285 / 398.4Syn Z: 0.70

ClinVar Variant Classifications

211 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS125

Likely Benign49

Benign14

Conflicting1

Pathogenic

125

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	2	0	2
Likely Pathogenic	0	0	0	0	0
VUS	2	117	5	1	125
Likely Benign	0	4	16	29	49
Benign	0	2	7	5	14
Conflicting	—				1
Total	2	123	30	35	191

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

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12 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap KLC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →