KIF1C

Chr 17AR

kinesin family member 1C

Also known as: LTXS1, SATX2, SAX2, SPAX2, SPG58

NCBI Gene: 10749 ENSG00000129250 UniProt: O43896 OMIM: 603060

KIF1C encodes a kinesin motor protein required for retrograde transport of Golgi vesicles to the endoplasmic reticulum and has microtubule plus end-directed motility. Mutations cause spastic ataxia 2, an autosomal recessive disorder affecting the central nervous system with both spasticity and ataxia features. The gene shows significant constraint against loss-of-function variants (LOEUF 0.341), suggesting intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. Mutations in this gene are a cause of spastic ataxia 2, autosomal recessive. [provided by RefSeq, May 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spastic ataxia 2, autosomal recessiveMIM #611302

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Spastic ataxia 2, autosomal recessive; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.34

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.718

Z-score 5.52

OE 0.21 (0.13–0.34)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.40Z-score

OE missense 0.85 (0.79–0.91)

585 obs / 688.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.13–0.34)

0≤0.351.4

Missense OE?0.85 (0.79–0.91)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 12 / 57.0Missense obs/exp: 585 / 688.5Syn Z: -1.29

Background carrier burden — how many people carry a rare variant somewhere in KIF1C?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 45

1,398 rare PASS variants

Rare truncating (LoF)

1 in 1,500

168 rare PASS variants

Rare synonymous (reference)

1 in 63

676 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KIF1C. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 57	1 in 1,500
South Asian	~43k	1 in 30	1 in 2,000
Remaining (unassigned)	~30k	1 in 35	1 in 1,800
European (Finnish)	~27k	1 in 99	1 in 3,600
Admixed American	~22k	1 in 29	1 in 1,600
African / African American	~21k	1 in 36	1 in 1,100
East Asian	~20k	1 in 46	1 in 2,200
Ashkenazi Jewish	~13k	1 in 100	≈ 1 in 4,200
Middle Eastern	~2,884	1 in 31	≈ 1 in 680

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 21 coding exons well covered in gnomAD exomes and genomes.? see exons ↓