SPART

Summary

SPART (spartin, HGNC:18514) is a protein-coding gene on chromosome 13q13.3, encoding Spartin (Q8N0X7). Lipophagy receptor that plays an important role in lipid droplet (LD) turnover in motor neurons.

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).

Source: NCBI Gene 23111 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Troyer syndrome (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 419 total — 17 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 77
• MANE Select transcript: NM_015087

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18514
Approved symbol	SPART
Name	spartin
Location	13q13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0610, TAHCCP1
Ensembl gene	ENSG00000133104
Ensembl biotype	protein_coding
OMIM	607111
Entrez	23111

Gene structure

Transcript identifiers

Ensembl transcripts: 64 — 57 protein_coding, 7 protein_coding_CDS_not_defined

ENST00000355182, ENST00000438666, ENST00000451493, ENST00000460126, ENST00000475603, ENST00000476377, ENST00000482146, ENST00000491805, ENST00000494062, ENST00000494703, ENST00000495510, ENST00000650221, ENST00000888906, ENST00000888907, ENST00000888908, ENST00000888909, ENST00000888910, ENST00000888911, ENST00000888912, ENST00000888913, ENST00000888914, ENST00000888915, ENST00000888916, ENST00000888917, ENST00000888918, ENST00000888919, ENST00000888920, ENST00000888921, ENST00000888922, ENST00000888923, ENST00000888924, ENST00000888925, ENST00000888926, ENST00000888927, ENST00000888928, ENST00000888929, ENST00000888930, ENST00000888931, ENST00000888932, ENST00000888933, ENST00000888934, ENST00000888935, ENST00000888936, ENST00000888937, ENST00000888938, ENST00000929600, ENST00000929601, ENST00000929602, ENST00000929603, ENST00000929604, ENST00000929605, ENST00000929606, ENST00000929607, ENST00000929608, ENST00000929609, ENST00000929610, ENST00000929611, ENST00000961052, ENST00000961053, ENST00000961054, ENST00000961055, ENST00000961056, ENST00000961057, ENST00000961058

RefSeq mRNA: 4 — MANE Select: NM_015087 NM_001142294, NM_001142295, NM_001142296, NM_015087

CCDS: CCDS9356

Canonical transcript exons

ENST00000438666 — 9 exons

Exon	Start	End
ENSE00001919239	36301638	36304632
ENSE00003310651	36314227	36314421
ENSE00003403829	36326575	36326698
ENSE00003525764	36312145	36312235
ENSE00003549644	36312319	36312477
ENSE00003553999	36329362	36329517
ENSE00003615283	36331399	36331596
ENSE00003687805	36335021	36335832
ENSE00003844623	36346225	36346394

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.9750 / max 651.2898, expressed in 1779 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136782	31.6377	1707
136785	7.3163	1495
136786	5.2314	1525
136784	3.7111	1446
136781	1.5481	602
136783	0.8263	516
136778	0.6274	249
136788	0.3716	68
136789	0.2609	68
136787	0.2595	63

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.82	gold quality
adrenal tissue	UBERON:0018303	97.80	gold quality
left ovary	UBERON:0002119	97.31	gold quality
right ovary	UBERON:0002118	97.13	gold quality
endocervix	UBERON:0000458	96.69	gold quality
left uterine tube	UBERON:0001303	96.60	gold quality
popliteal artery	UBERON:0002250	96.49	gold quality
tibial artery	UBERON:0007610	96.49	gold quality
right adrenal gland cortex	UBERON:0035827	96.46	gold quality
stromal cell of endometrium	CL:0002255	96.45	gold quality
right adrenal gland	UBERON:0001233	96.31	gold quality
left adrenal gland	UBERON:0001234	96.31	gold quality
body of uterus	UBERON:0009853	96.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.19	gold quality
left adrenal gland cortex	UBERON:0035825	96.07	gold quality
mucosa of stomach	UBERON:0001199	95.99	gold quality
ovary	UBERON:0000992	95.95	gold quality
gall bladder	UBERON:0002110	95.91	gold quality
adrenal gland	UBERON:0002369	95.85	gold quality
aorta	UBERON:0000947	95.73	gold quality
adrenal cortex	UBERON:0001235	95.72	gold quality
ventricular zone	UBERON:0003053	95.70	gold quality
corpus callosum	UBERON:0002336	95.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.53	gold quality
lower esophagus	UBERON:0013473	95.49	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.48	gold quality
tibial nerve	UBERON:0001323	95.43	gold quality
descending thoracic aorta	UBERON:0002345	95.35	gold quality
spinal cord	UBERON:0002240	95.25	gold quality
omental fat pad	UBERON:0010414	95.25	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, GLI2, WWP1

miRNA regulators (miRDB)

123 targeting SPART, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-551B-5P	99.96	71.28	3493

Literature-anchored findings (GeneRIF, showing 24)

• SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia.We report mapping of the TRS locus to chromosome 13q12.3 and identify a frameshift mutation in SPG20, encoding spartin (PMID:12134148)
• Our results suggest that spartin might be involved in endocytosis, vesicle trafficking, or mitogenic activity, and that impairment in one of these processes may underlie the long axonopathy in patients with Troyer syndrome. (PMID:16036216)
• This study provides the first evidence of spartin subcellular localization and identifies it as the third mitochondrial protein implicated in hereditary spastic paraplegia. (PMID:16945107)
• overexpression of spartin results in a prominent decrease in EGFR degradation (PMID:17332501)
• We describe a new family with Troyer syndrome due to the 1110delA mutation. (PMID:18413476)
• experiments suggest functions for ubiquitin ligases and SPG20 in the regulation of lipid droplet turnover and potential pathological mechanisms in Troyer syndrome. (PMID:19307600)
• SPG20 interacts with endosomes and AIP4 and AIP5. (PMID:19580544)
• The hereditary spastic paraplegia proteins NIPA1, spastin and spartin inhibit BMP signalling by promoting BMP receptors degradation. (PMID:19620182)
• Spartin acts as an adaptor protein that activates and recruits AIP4 E3 ubiquitin ligase to lipid droplets and by this means regulates the level of ubiquitination of adipophilin. (PMID:20504295)
• These data suggest that Ist1 interaction is important for spartin recruitment to the midbody and that spartin participates in cytokinesis. (PMID:20719964)
• The present study identifies SPG20 promoter hypermethylation as a biomarker suitable for non-invasive detection of colorectal cancer, and a possible mechanism for cytokinesis arrest in colorectal tumorigenesis. (PMID:21499309)
• SPG20 protein spartin associates with cardiolipin via its plant-related senescence domain and regulates mitochondrial Ca2+ homeostasis (PMID:21559443)
• The study reveals that hypermethylation in Spastic paraplegia-20 promoter is a highly specific and sensitive biomarker for screening colorectal cancer in stool samples as a noninvasive method. (PMID:23372428)
• Spartin regulates both synaptic development and neuronal survival by controlling microtubule stability via the BMP-Drosophila fragile X mental retardation protein-Futsch pathway. (PMID:23439121)
• hypermethylation of the spastic paraplegia-20 promoter occurred frequently in gastric cancer. (PMID:24381142)
• Up-regulation of SPG20 expression, brought about by trisomy 13 in colon cancer cells trisomy 13 amniocytes, is sufficient for the cytokinesis failure phenotype. (PMID:25942454)
• Study identified mutation in SPG20 as the disease causing mutation for Troyer Syndrome in Turkish siblings. (PMID:26003402)
• we report the clinical findings in three brothers of a consanguineous Moroccan family, aged 24, 17, and 7 yr old, with spastic paraplegia, short stature, motor and cognitive delay, and severe intellectual disability. Targeted exon capture and sequencing showed a homozygous nonsense mutation in the SPG20 gene, c.1369C>T (p.Arg457*), in the three affected boys. (PMID:28679690)
• Methylation-induced Spastic paraplegia 20 silencing facilitates gastric cancer cell proliferation by activating the EGFR/MAPK signaling pathway. (PMID:29673586)
• hypermethylation status of SPG20 gene promoter is significantly associated with intra-hepatic metastasis and contribute to HCC metastasis (PMID:31109594)
• The novel mutation in SPART leads to a profound bioenergetic imbalance. (PMID:31314595)
• KLF4, DAPK1 and SPG20 promoter methylation is not affected by DNMT1 silencing and hypomethylating drugs in lymphoma cells. (PMID:34751409)
• Spastic Paraplegia 20 and Serine/Threonine Protein Kinase 31 Expression for the Detection of Colorectal Cancer. (PMID:35389570)
• Lysosomal damage sensing and lysophagy initiation by SPG20-ITCH. (PMID:38503285)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sparta	ENSDARG00000068782
danio_rerio	spartb	ENSDARG00000103457
mus_musculus	Spart	ENSMUSG00000036580
rattus_norvegicus	Spart	ENSRNOG00000014155
drosophila_melanogaster	spartin	FBGN0037265
caenorhabditis_elegans	spg-20	WBGENE00019006

Protein

Protein identifiers

Spartin — Q8N0X7 (reviewed: Q8N0X7)

Alternative names: Spastic paraplegia 20 protein, Trans-activated by hepatitis C virus core protein 1

All UniProt accessions (2): A0A024RDV9, Q8N0X7

UniProt curated annotations — full annotation on UniProt →

Function. Lipophagy receptor that plays an important role in lipid droplet (LD) turnover in motor neurons. Localizes to LDs and interacts with components of the autophagy machinery, such as MAP1LC3A/C proteins to deliver LDs to autophagosomes for degradation via lipophagy. Lipid transfer protein required for lipid droplet degradation, including by lipophagy. Can bind and transfer all lipid species found in lipid droplets, from phospholipids to triglycerides and sterol esters but the direction of lipid transfer by spartin and its cargos are unknown. May be implicated in endosomal trafficking, or microtubule dynamics, or both. Participates in cytokinesis.

Subunit / interactions. Interacts with ITCH and WWP1. Interacts (via MIT domain) with IST1; leading to the recruitment of SPART to midbodies. Interacts with MAP1LC3A and MAP1LC3C.

Subcellular location. Cytoplasm. Midbody. Lipid droplet.

Tissue specificity. Ubiquitously expressed, with highest levels of expression detected in adipose tissue.

Post-translational modifications. Ubiquitinated; ubiquitination does not require ITCH and WWP1.

Disease relevance. Spastic paraplegia 20, autosomal recessive (SPG20) [MIM:275900] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG20 is characterized by dysarthria, distal amyotrophy, mild developmental delay and short stature. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The senescence domain is required and sufficient for lipid transfer.

RefSeq proteins (4): NP_001135766, NP_001135767, NP_001135768, NP_055902* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007330	MIT_dom	Domain
IPR009686	Senescence/spartin_C	Domain
IPR036181	MIT_dom_sf	Homologous_superfamily
IPR045036	Spartin-like	Family

Pfam: PF06911

UniProt features (30 total): mutagenesis site 8, region of interest 5, compositionally biased region 3, helix 3, domain 2, modified residue 2, sequence variant 2, sequence conflict 2, chain 1, cross-link 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4U7I	X-RAY DIFFRACTION	1.79
2DL1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N0X7-F1	63.03	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 1, 470, 362

Mutagenesis-validated functional residues (8):

Position	Phenotype
24	abolishes interaction with ist1. does not localize to the midbody.
171–174	abolishes interaction with itch and wwp1.
438	abolishes localization to lipid droplets; when associated with a-449; a-460; a-479; a-490 and a-501.
449	abolishes localization to lipid droplets; when associated with a-438; a-460; a-479; a-490 and a-501.
460	abolishes localization to lipid droplets; when associated with a-438; a-449; a-479; a-490 and a-501.
479	abolishes localization to lipid droplets; when associated with a-438; a-449; a-460; a-490 and a-501.
490	abolishes localization to lipid droplets; when associated with a-438; a-449; a-460; a-479 and a-501.
501	abolishes localization to lipid droplets; when associated with a-438; a-449; a-460; a-479 and a-490.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 383 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, TOMLINS_PROSTATE_CANCER_DN, GOBP_CYTOKINETIC_PROCESS, chr13q13

GO Biological Process (15): lipid transport (GO:0006869), lipid catabolic process (GO:0016042), BMP signaling pathway (GO:0030509), negative regulation of BMP signaling pathway (GO:0030514), lipid droplet organization (GO:0034389), collateral sprouting in absence of injury (GO:0048669), negative regulation of collateral sprouting in absence of injury (GO:0048698), neuromuscular process (GO:0050905), cell division (GO:0051301), regulation of mitochondrial membrane potential (GO:0051881), adipose tissue development (GO:0060612), lipophagy (GO:0061724), midbody abscission (GO:0061952), lipid metabolic process (GO:0006629), regulation of biological quality (GO:0065008)

GO Molecular Function (3): lipid binding (GO:0008289), ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), lipid droplet (GO:0005811), cytosol (GO:0005829), plasma membrane (GO:0005886), midbody (GO:0030496), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
transport	1
lipid localization	1
lipid metabolic process	1
catabolic process	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
organelle organization	1
collateral sprouting	1
collateral sprouting in absence of injury	1
negative regulation of collateral sprouting	1
regulation of collateral sprouting in absence of injury	1
nervous system process	1
cellular process	1
regulation of membrane potential	1
animal organ development	1
connective tissue development	1
macroautophagy	1
lipid droplet disassembly	1
membrane organization	1
mitotic cytokinetic process	1
primary metabolic process	1
biological regulation	1
ubiquitin-like protein ligase binding	1
intracellular anatomical structure	1
mitochondrial membrane	1
organelle outer membrane	1
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPART	HLA-C	P04222	970
SPART	SORBS1	Q9BX66	956
SPART	EPS15	P42566	933
SPART	NIPA1	Q7RTP0	893
SPART	STAC	Q99469	889
SPART	PNPLA6	Q8IY17	882
SPART	TRIM45	Q9H8W5	880
SPART	SPG21	Q9NZD8	876
SPART	ATL2	Q8NHH9	861
SPART	ATL3	Q6DD88	854
SPART	SPG11	Q96JI7	851
SPART	ATL1	Q8WXF7	841
SPART	FCHSD2	O94868	840
SPART	SPG7	Q9UQ90	823
SPART	KIR3DL3	Q8N743	806

IntAct

107 interactions, top by confidence:

A	B	Type	Score
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
rep	GTF2F2	psi-mi:“MI:0914”(association)	0.730
RAD17	RFC4	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SPART	ITCH	psi-mi:“MI:0914”(association)	0.640
OTULIN	SPART	psi-mi:“MI:0915”(physical association)	0.560
SPART	DESI2	psi-mi:“MI:0915”(physical association)	0.560
RABGEF1	SPART	psi-mi:“MI:0915”(physical association)	0.560
UBAC1	SPART	psi-mi:“MI:0915”(physical association)	0.560
USP5	SPART	psi-mi:“MI:0915”(physical association)	0.560
SPART	OTUB2	psi-mi:“MI:0915”(physical association)	0.560
OTUD7B	SPART	psi-mi:“MI:0915”(physical association)	0.560
EPN2	SPART	psi-mi:“MI:0915”(physical association)	0.560
SPART	OTULIN	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1A	SPART	psi-mi:“MI:0915”(physical association)	0.560
SPART	RABGEF1	psi-mi:“MI:0915”(physical association)	0.560
SPART	UBAC1	psi-mi:“MI:0915”(physical association)	0.560
YOD1	SPART	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (162): SPG20 (Biochemical Activity), SPG20 (Co-fractionation), SPG20 (Co-fractionation), SPG20 (Co-fractionation), SPG20 (Affinity Capture-MS), SPG20 (Proximity Label-MS), SPG20 (Affinity Capture-MS), SPG20 (Affinity Capture-MS), SPG20 (Affinity Capture-MS), SPG20 (Affinity Capture-MS), SPG20 (Biochemical Activity), SPG20 (Affinity Capture-MS), POLK (Affinity Capture-MS), SMURF1 (Affinity Capture-MS), ITCH (Affinity Capture-MS)

ESM2 similar proteins: A0JNJ3, A0M8T5, A4IG66, F1Q930, F7AEX0, O00750, O15327, O48832, O94876, P35612, P97578, Q00PJ1, Q05764, Q07E15, Q07E28, Q09YG9, Q0P4J3, Q155Q3, Q1JPG0, Q2QLA2, Q2T9N1, Q2TBG9, Q2VUH7, Q3ZC62, Q4R4D7, Q4V8E4, Q5BJ78, Q5BLE2, Q5JTW2, Q5R5V7, Q5RA60, Q5T1M5, Q69ZZ6, Q6GR21, Q6INU2, Q6IP02, Q6NTW1, Q8BG50, Q8C5W4, Q8C6E0

Diamond homologs: A0JNJ3, A2VDN5, A7T395, B2RYN7, B7PXE3, Q05AS3, Q5ZK92, Q6AZT2, Q6NW58, Q719N1, Q8N0X7, Q8R1X6, Q9QYY8, Q9UBP0, Q9VN45

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SPART	“up-regulates activity”	ITCH	binding
SPART	“up-regulates activity”	WWP1	binding
ITCH	“up-regulates activity”	SPART	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

419 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	11
Uncertain significance	235
Likely benign	113
Benign	14

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1070060	NM_015087.5(SPART):c.1294del (p.Ser432fs)	Pathogenic
1687408	NM_015087.5(SPART):c.894_898del (p.Met299fs)	Pathogenic
183277	NM_015087.5(SPART):c.1450dup (p.Thr484fs)	Pathogenic
1949967	NM_015087.5(SPART):c.844_847del (p.Arg282fs)	Pathogenic
2184607	NM_015087.5(SPART):c.553_554del (p.Val185fs)	Pathogenic
3244218	NC_000013.10:g.(?36878502)(36909967_?)del	Pathogenic
3457	NM_015087.5(SPART):c.1110del (p.Lys370fs)	Pathogenic
3458	NM_015087.5(SPART):c.364_365del (p.Met122fs)	Pathogenic
3706426	NM_015087.5(SPART):c.253_254del (p.Leu85fs)	Pathogenic
3725614	NM_015087.5(SPART):c.1257G>A (p.Trp419Ter)	Pathogenic
379832	NM_015087.5(SPART):c.1369C>T (p.Arg457Ter)	Pathogenic
419124	NM_015087.5(SPART):c.696del (p.Phe232fs)	Pathogenic
4753217	NM_015087.5(SPART):c.853_856del (p.Pro284_Val285insTer)	Pathogenic
572922	NM_015087.5(SPART):c.685C>T (p.Gln229Ter)	Pathogenic
631700	NM_015087.5(SPART):c.475_476del (p.Leu159fs)	Pathogenic
863112	NM_015087.5(SPART):c.388C>T (p.Gln130Ter)	Pathogenic
989199	NM_015087.5(SPART):c.1474_1477del (p.Gln492fs)	Pathogenic
1333334	NM_015087.5(SPART):c.592G>T (p.Gly198Ter)	Likely pathogenic
1700149	NM_015087.5(SPART):c.621del (p.Gln207fs)	Likely pathogenic
191283	Single allele	Likely pathogenic
2503433	NM_015087.5(SPART):c.1643-2A>G	Likely pathogenic
2643770	NM_015087.5(SPART):c.885dup (p.Pro296fs)	Likely pathogenic
3383993	NM_015087.5(SPART):c.1324G>C (p.Ala442Pro)	Likely pathogenic
3775802	NM_015087.5(SPART):c.1738G>T (p.Gly580Ter)	Likely pathogenic
4705815	NM_015087.5(SPART):c.1008+1G>C	Likely pathogenic
4738543	NM_015087.5(SPART):c.1483+1G>A	Likely pathogenic
546727	NM_015087.5(SPART):c.1794dup (p.Val599fs)	Likely pathogenic
546728	NM_015087.5(SPART):c.712G>T (p.Glu238Ter)	Likely pathogenic

SpliceAI

2226 predictions. Top by Δscore:

Variant	Effect	Δscore
13:36304628:CGTAT:C	acceptor_gain	1.0000
13:36304630:TAT:T	acceptor_gain	1.0000
13:36304630:TATCT:T	acceptor_loss	1.0000
13:36304633:C:CC	acceptor_gain	1.0000
13:36304634:T:C	acceptor_gain	1.0000
13:36304634:T:TC	acceptor_gain	1.0000
13:36304635:T:C	acceptor_gain	1.0000
13:36304635:T:TC	acceptor_gain	1.0000
13:36304647:T:TC	acceptor_gain	1.0000
13:36312140:CTT:C	donor_loss	1.0000
13:36312141:TTA:T	donor_loss	1.0000
13:36312142:TA:T	donor_loss	1.0000
13:36312143:A:AC	donor_gain	1.0000
13:36312143:AC:A	donor_loss	1.0000
13:36312144:C:CG	donor_gain	1.0000
13:36312144:CT:C	donor_gain	1.0000
13:36312144:CTT:C	donor_gain	1.0000
13:36312144:CTTG:C	donor_gain	1.0000
13:36312144:CTTGT:C	donor_gain	1.0000
13:36312231:AAATC:A	acceptor_gain	1.0000
13:36312232:AATC:A	acceptor_gain	1.0000
13:36312233:ATC:A	acceptor_gain	1.0000
13:36312234:TC:T	acceptor_gain	1.0000
13:36312234:TCCT:T	acceptor_loss	1.0000
13:36312235:CC:C	acceptor_gain	1.0000
13:36312235:CCTG:C	acceptor_loss	1.0000
13:36312236:C:CC	acceptor_gain	1.0000
13:36312237:T:A	acceptor_loss	1.0000
13:36312475:CAA:C	acceptor_gain	1.0000
13:36312478:C:CC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000022833 (13:36365755 A>C), RS1000095221 (13:36305477 C>T), RS1000109447 (13:36351923 G>C), RS1000120288 (13:36348872 T>C), RS1000208178 (13:36332942 T>C), RS1000212262 (13:36339049 A>G), RS1000237531 (13:36367997 A>G), RS1000239353 (13:36332667 C>G), RS1000327434 (13:36328709 A>G), RS1000407098 (13:36349226 G>T), RS1000483757 (13:36325109 G>A), RS1000489855 (13:36370335 G>A), RS1000502136 (13:36357267 T>C), RS1000538405 (13:36313020 A>G), RS1000541157 (13:36338926 C>T)

Disease associations

OMIM: gene MIM:607111 | disease phenotypes: MIM:303350, MIM:275900

GenCC curated gene-disease

Disease	Classification	Inheritance
Troyer syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Troyer syndrome	Definitive	AR

Mondo (5): hereditary spastic paraplegia (MONDO:0019064), Troyer syndrome (MONDO:0010156), cerebellar ataxia (MONDO:0000437), microcephaly (MONDO:0001149), strabismus (MONDO:0003432)

Orphanet (3): Hereditary spastic paraplegia (Orphanet:685), Autosomal recessive spastic paraplegia type 20 (Orphanet:101000), Rare ataxia (Orphanet:102002)

HPO phenotypes

77 total (30 of 77 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000126	Hydronephrosis
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000369	Low-set ears
HP:0000448	Prominent nose
HP:0000494	Downslanted palpebral fissures
HP:0000639	Nystagmus
HP:0000709	Psychosis
HP:0000712	Emotional lability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000924	Abnormality of the skeletal system
HP:0001155	Abnormality of the hand
HP:0001156	Brachydactyly
HP:0001172	Abnormal thumb morphology
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001310	Dysmetria
HP:0001317	Abnormal cerebellum morphology

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008399_20	Cocaine dependence	2.000000e-06

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
D013285	Strabismus	C10.292.562.887; C11.590.810
C536858	Spastic paraplegia 20, autosomal recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	increases expression	1
corosolic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Zoledronic Acid	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Coumestrol	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Methotrexate	affects response to substance	1
Methyl Methanesulfonate	decreases expression	1
Ribonucleotides	affects binding	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F1TK	HyCyte SH-SY5Y KO-hSPART	Cancer cell line	Female

Clinical trials (associated diseases)

297 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740	PHASE4	COMPLETED	C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
NCT00461656	PHASE4	COMPLETED	Povidone-iodine Antisepsis for Strabismus Surgery
NCT01901588	PHASE4	COMPLETED	Efficacy of Single-Shot Dexmedetomidine Versus Placebo in Preventing Pediatric Emergence Delirium in Strabismus Surgery
NCT02379546	PHASE4	COMPLETED	The Effect of Anaesthesia Depth on Oculo-cardiac Reflex
NCT03349515	PHASE4	COMPLETED	The Effect of Povidone-iodine Ophthalmic Surgical Prep Solution on Respiration in Children Undergoing Strabismus Surgery With General Anesthesia.
NCT04549844	PHASE4	UNKNOWN	Peribulbar Block for Prevention of Oculocardiac Reflex
NCT06035757	PHASE4	RECRUITING	The Occurrence of Emergence Agitation in Pediatric Strabismus Surgery
NCT06560268	PHASE4	NOT_YET_RECRUITING	Low Flow Anesthesia in Children Undergoing Strabismus Surgery
NCT01970098	PHASE3	COMPLETED	A Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111	PHASE3	COMPLETED	An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124	PHASE3	COMPLETED	A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137	PHASE3	COMPLETED	A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302	PHASE3	COMPLETED	An Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137	PHASE3	RECRUITING	Confirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT00000128	PHASE3	UNKNOWN	A Trial of Bifocals in Myopic Children With Esophoria
NCT00001864	PHASE3	COMPLETED	Amblyopia (Lazy Eye) Treatment Study
NCT00038753	PHASE3	UNKNOWN	Vision In Preschoolers Study (VIP Study)
NCT01584843	PHASE3	COMPLETED	Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Strabismus
NCT04060771	PHASE3	UNKNOWN	Post-Operative Nausea and Vomiting in Children Submitted to Strabismus Surgery
NCT06863675	PHASE3	NOT_YET_RECRUITING	Highly Aspherical Lenslet (HAL) and Binocular Vision (BV) Disorders [HALT X(T) Study]
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT00034242	PHASE2	COMPLETED	High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00863538	PHASE2	COMPLETED	Phase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01004016	PHASE2	COMPLETED	A Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01350440	PHASE2	COMPLETED	Safety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia
NCT02540655	PHASE2	COMPLETED	Efficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT03932669	PHASE2	COMPLETED	Effect of Nilotinib in Cerebellar Ataxia Patients
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT05125666	PHASE2	UNKNOWN	Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
NCT06397274	PHASE2	NOT_YET_RECRUITING	Stemchymal® for Polyglutamine Spinocerebellar Ataxia
NCT00478907	PHASE2	COMPLETED	Prevention of Complications of Eye Surgery
NCT06689943	PHASE2	NOT_YET_RECRUITING	Pain After Strabismus Surgery
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals