SPART

Chr 13AR

spartin

Also known as: SPG20, TAHCCP1

NCBI Gene: 23111 ENSG00000133104 UniProt: Q8N0X7 OMIM: 607111

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

GOFmechanismARLOEUF 0.841 OMIM phenotype

Clinical Summary— SPART

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Gene-Disease Validity (ClinGen)

Troyer syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.22

OE 0.54 (0.36–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.07Z-score

OE missense 0.99 (0.91–1.08)

346 obs / 349.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.36–0.84)

0≤0.351.4

Missense OE?0.99 (0.91–1.08)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 15 / 27.5Missense obs/exp: 346 / 349.7Syn Z: 0.01

This gene — mechanism propensity

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.