KIF6

Chr 6

kinesin family member 6

Also known as: C6orf102, dJ1043E3.1, dJ137F1.4, dJ188D3.1

NCBI Gene: 221458 ENSG00000164627 UniProt: Q6ZMV9

This protein functions as a molecular motor that transports protein complexes, organelles, and mRNA along microtubules within cells. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq

This gene encodes a member of a family of molecular motors which are involved in intracellular transport of protein complexes, membrane organelles, and messenger ribonucleic acid along microtubules. Kinesins function as homodimeric molecules with two N-terminal head domains that move along microtubules and two C-terminal tail domains that interact with the transported cargo, either directly or indirectly, through adapter molecules. This gene is ubiquitously expressed in coronary arteries and other vascular tissue. A naturally occurring mutation in this gene is associated with coronary heart disease. [provided by RefSeq, May 2017]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.10

Clinical Summary— KIF6

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

113 VUS of 136 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

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.000

Z-score 0.93

OE 0.86 (0.68–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.43Z-score

OE missense 0.94 (0.87–1.02)

408 obs / 433.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.86 (0.68–1.10)

0≤0.351.4

Missense OE?0.94 (0.87–1.02)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 45 / 52.2Missense obs/exp: 408 / 433.4Syn Z: 1.21

This gene — mechanism propensity

0.77top 25%

GOF

0.6444th %ile

LOF

0.3551th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

136 submitted variants in ClinVar

ClinVar

Classification Summary

VUS113

Likely Benign4

113

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	112	0	113
Likely Benign	0	3	1	4
Benign	0	0	0	0
Total	1	115	1	117

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap KIF6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →