SPART

Chr 13AR

spartin

Also known as: SPG20, TAHCCP1

The encoded protein functions as a lipophagy receptor that regulates lipid droplet turnover in motor neurons and serves as a lipid transfer protein, while also participating in endosomal trafficking and cytokinesis. Mutations cause Troyer syndrome, an autosomal recessive spastic paraplegia characterized by spasticity and neurological dysfunction. This gene shows low constraint against loss-of-function variants (LOEUF 0.838), consistent with its recessive inheritance pattern where biallelic mutations are required for disease manifestation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismARLOEUF 0.841 OMIM phenotype
Clinical SummarySPART
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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.
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ClinVar Variants
79 unique Pathogenic / Likely Pathogenic· 239 VUS of 472 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.22
OE 0.54 (0.360.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.07Z-score
OE missense 0.99 (0.911.08)
346 obs / 349.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.360.84)
00.351.4
Missense OE0.99 (0.911.08)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 15 / 27.5Missense obs/exp: 346 / 349.7Syn Z: 0.01
DN
0.5870th %ile
GOF
0.6444th %ile
LOF
0.3745th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

472 submitted variants in ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic13
VUS239
Likely Benign115
Benign14
Conflicting16
66
Pathogenic
13
Likely Pathogenic
239
VUS
115
Likely Benign
14
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
0
50
0
66
Likely Pathogenic
11
1
1
0
13
VUS
6
183
45
5
239
Likely Benign
1
6
37
71
115
Benign
0
0
13
1
14
Conflicting
16
Total3419014677463

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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