KIF1A

Chr 2ADAR

kinesin family member 1A

Also known as: ATSV, C2orf20, HSN2C, MRD9, NESCAVS, SPG30, SPG30A, SPG30B

NCBI Gene: 547ENSG00000130294UniProt: Q12756OMIM: 601255

The protein functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations cause a spectrum of disorders including NESCAV syndrome, hereditary sensory neuropathy type IIC, and spastic paraplegia 30 through both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves loss of function of this essential neuronal transport protein.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD/ARLOEUF 0.144 OMIM phenotypes
Clinical Summary— KIF1A
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 201 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 8.44
OE 0.07 (0.04–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
5.16Z-score
OE missense 0.57 (0.53–0.61)
640 obs / 1127.3 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.07 (0.04–0.14)
0≤0.351.4
Missense OE0.57 (0.53–0.61)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 7 / 96.4Missense obs/exp: 640 / 1127.3Syn Z: 0.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveKIF1A-related NESCAV syndromeOTHERAD
definitiveKIF1A-related neuropathy, hereditary sensoryLOFAR
DN
0.5477th %ile
GOF
0.5758th %ile
LOF
0.66top 25%

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

LOFprediction above median · 1 literature citation · 54% of P/LP variants are LoF · LOEUF 0.14
DN1 literature citation

Literature Evidence

DNAutosomal dominant transmission of complicated hereditary spastic paraplegia due to a dominant negative mutation of KIF1A, SPG30 gene.PMID:28970574
LOFThe identification of KIF1A loss-of-function variants suggests haploinsufficiency as a possible mechanism in autosomal dominant spastic paraplegia.PMID:31488895

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic10
VUS201
Likely Benign126
Benign5
Conflicting42
16
Pathogenic
10
Likely Pathogenic
201
VUS
126
Likely Benign
5
Benign
42
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
2
4
0
16
Likely Pathogenic
4
6
0
0
10
VUS
2
167
25
7
201
Likely Benign
0
20
57
49
126
Benign
0
3
1
1
5
Conflicting
—42
Total161988757400

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

View in ClinVar →

Protein Context — Lollipop Plot

KIF1A · 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
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