SPART

Chr 13AR

spartin

Also known as: SPG20, TAHCCP1

NCBI Gene: 23111ENSG00000133104UniProt: Q8N0X7

This gene encodes a protein containing a MIT (Microtubule Interacting and Trafficking molecule) domain, and is implicated in regulating endosomal trafficking and mitochondria function. The protein localizes to mitochondria and partially co-localizes with microtubules. Stimulation with epidermal growth factor (EGF) results in protein translocation to the plasma membrane, and the protein functions in the degradation and intracellular trafficking of EGF receptor. Multiple alternatively spliced variants, encoding the same protein, have been identified. Mutations associated with this gene cause autosomal recessive spastic paraplegia 20 (Troyer syndrome). [provided by RefSeq, Nov 2008]

Primary Disease Associations & Inheritance

Troyer syndromeMIM #275900
AR
UniProtSpastic paraplegia 20, autosomal recessive
462
ClinVar variants
78
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SPART
🧬
Gene-Disease Validity (ClinGen)
Troyer syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
78 Pathogenic / Likely Pathogenic· 240 VUS of 462 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.84LOEUF
pLI 0.000
Z-score 2.22
OE 0.54 (0.36–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.07Z-score
OE missense 0.99 (0.91–1.08)
346 obs / 349.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.54 (0.36–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.91–1.08)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 15 / 27.5Missense obs/exp: 346 / 349.7Syn Z: 0.01

ClinVar Variant Classifications

462 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic65
Likely Pathogenic13
VUS240
Likely Benign114
Benign14
Conflicting16
65
Pathogenic
13
Likely Pathogenic
240
VUS
114
Likely Benign
14
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
54
0
65
Likely Pathogenic
8
1
4
0
13
VUS
4
180
51
5
240
Likely Benign
1
6
37
70
114
Benign
0
0
13
1
14
Conflicting
—16
Total2418715976462

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

View in ClinVar →

Protein Context — Lollipop Plot

SPART · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SPARTIN; SPART
MIM #607111 · *

Troyer syndrome

MIM #275900

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SPART
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by Coenzyme Q.
Diquigiovanni C et al.·Open Biol
2023Case report
Genotype variability in early-onset Hereditary Spastic Paraplegia: a single-center study.
Colona VL et al.·Eur J Paediatr Neurol
2025
Memory-guided navigation in amyotrophic lateral sclerosis.
Maier PM et al.·J Neurol
2023
Qualitative development and content validation of the "SPART" model; a focused ethnography study of observable diagnostic and therapeutic activities in the emergency medical services care process.
Dercksen B et al.·BMC Emerg Med
2021Functional
The nature, sequence and duration of professional activities of Emergency Medical Service providers: An observational study to evaluate quality of care using the steps in the EMS care process as described by the SPART model.
Dercksen B et al.·PLoS One
2024Functional
A novel neutrophil extracellular traps-related lncRNA signature predicts prognosis in patients with early-stage lung adenocarcinoma.
Wang H et al.·Ann Med
2023Cohort
Maternal uniparental isodisomy in a patient with autosomal recessive spastic paraplegia type 20.
Borgione E et al.·Gene
2025Case report
Charting the genetic landscape of autosomal recessive hereditary spastic paraplegia: A deep dive into 10 exceptionally rare cases.
Yigit ZM et al.·Neurogenetics
2025Cohort
Visuospatial memory profile of patients with Parkinson's disease.
França M et al.·Appl Neuropsychol Adult
2025Cohort
[Developmental and epileptic encephalopathy produced by the ATP1A2 mutation].
Rudenskaya GE et al.·Zh Nevrol Psikhiatr Im S S Korsakova
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools