ZFYVE27

Summary

ZFYVE27 (zinc finger FYVE-type containing 27, HGNC:26559) is a protein-coding gene on chromosome 10q24.2, encoding Protrudin (Q5T4F4). Key regulator of RAB11-dependent vesicular trafficking during neurite extension through polarized membrane transport.

This gene encodes a protein with several transmembrane domains, a Rab11-binding domain and a lipid-binding FYVE finger domain. The encoded protein appears to promote neurite formation. A mutation in this gene has been reported to be associated with hereditary spastic paraplegia, however the pathogenicity of the mutation, which may simply represent a polymorphism, is unclear.

Source: NCBI Gene 118813 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary spastic paraplegia 33 (Limited, GenCC)
• Clinical variants (ClinVar): 268 total
• MANE Select transcript: NM_001385875

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26559
Approved symbol	ZFYVE27
Name	zinc finger FYVE-type containing 27
Location	10q24.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32919, SPG33
Ensembl gene	ENSG00000155256
Ensembl biotype	protein_coding
OMIM	610243
Entrez	118813

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 27 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000337540, ENST00000357540, ENST00000359980, ENST00000370610, ENST00000370613, ENST00000393677, ENST00000423811, ENST00000462887, ENST00000473237, ENST00000477521, ENST00000481956, ENST00000684270, ENST00000891775, ENST00000891776, ENST00000891777, ENST00000891778, ENST00000891779, ENST00000930130, ENST00000930131, ENST00000930132, ENST00000930133, ENST00000930134, ENST00000930135, ENST00000930136, ENST00000930137, ENST00000930138, ENST00000951156, ENST00000951157, ENST00000951158, ENST00000951159, ENST00000951160

RefSeq mRNA: 46 — MANE Select: NM_001385875 NM_001002261, NM_001002262, NM_001174119, NM_001174120, NM_001174121, NM_001174122, NM_001385871, NM_001385875, NM_001385876, NM_001385877, NM_001385878, NM_001385879, NM_001385880, NM_001385881, NM_001385882, NM_001385883, NM_001385884, NM_001385885, NM_001385886, NM_001385887, NM_001385888, NM_001385889, NM_001385890, NM_001385891, NM_001385892, NM_001385893, NM_001385894, NM_001385895, NM_001385896, NM_001385897, NM_001385898, NM_001385899, NM_001385900, NM_001385901, NM_001385902, NM_001385903, NM_001385904, NM_001385905, NM_001385906, NM_001385908, NM_001385911, NM_001385915, NM_001385916, NM_001385918, NM_001385919, NM_144588

CCDS: CCDS31262, CCDS31263, CCDS31264, CCDS53562, CCDS53563, CCDS53564, CCDS53565

Canonical transcript exons

ENST00000684270 — 13 exons

Exon	Start	End
ENSE00001019961	97750331	97750470
ENSE00001019964	97748269	97748364
ENSE00001019965	97749474	97749586
ENSE00001019974	97751391	97751462
ENSE00001097766	97753038	97753182
ENSE00001236963	97752857	97752877
ENSE00001236979	97757265	97757311
ENSE00001389121	97759236	97760895
ENSE00002274439	97738477	97738674
ENSE00003322645	97743094	97743164
ENSE00003493982	97757642	97757723
ENSE00003672279	97744729	97744915
ENSE00003921951	97737128	97737321

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2927 / max 267.7466, expressed in 1810 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106461	15.9193	1808
106462	1.0761	586
106460	0.2974	171

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	97.45	silver quality
right hemisphere of cerebellum	UBERON:0014890	95.04	gold quality
ileal mucosa	UBERON:0000331	94.89	gold quality
right uterine tube	UBERON:0001302	94.78	gold quality
cerebellar hemisphere	UBERON:0002245	94.73	gold quality
cerebellar cortex	UBERON:0002129	94.56	gold quality
adenohypophysis	UBERON:0002196	93.77	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.71	gold quality
left ovary	UBERON:0002119	93.67	gold quality
mucosa of transverse colon	UBERON:0004991	93.63	gold quality
right frontal lobe	UBERON:0002810	93.27	gold quality
right ovary	UBERON:0002118	93.21	gold quality
transverse colon	UBERON:0001157	93.19	gold quality
cerebellum	UBERON:0002037	93.14	gold quality
tibial nerve	UBERON:0001323	92.95	gold quality
pituitary gland	UBERON:0000007	92.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.46	gold quality
granulocyte	CL:0000094	92.35	gold quality
metanephros cortex	UBERON:0010533	91.91	gold quality
endocervix	UBERON:0000458	91.81	gold quality
body of pancreas	UBERON:0001150	91.74	gold quality
skin of leg	UBERON:0001511	91.45	gold quality
left adrenal gland cortex	UBERON:0035825	91.45	gold quality
minor salivary gland	UBERON:0001830	91.40	gold quality
right lobe of thyroid gland	UBERON:0001119	91.33	gold quality
small intestine	UBERON:0002108	91.31	gold quality
cortical plate	UBERON:0005343	91.30	gold quality
body of stomach	UBERON:0001161	91.27	gold quality
left adrenal gland	UBERON:0001234	91.25	gold quality
body of uterus	UBERON:0009853	91.25	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	83.35
E-ANND-3	no	3.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting ZFYVE27, 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-4283	100.00	66.42	2097
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-6837-5P	99.25	65.47	1632

Literature-anchored findings (GeneRIF, showing 11)

• Mutation affects neuronal intracellular trafficking in the corticospinal tract, which is consistent with the pathology of hereditary spastic paraplegia. (PMID:16826525)
• protrudin regulates Rab11-dependent membrane recycling to promote the directional membrane trafficking required for neurite formation [protrudin] (PMID:17082457)
• The role of ZFYVE27/protrudin in hereditary spastic paraplegia is reported. (PMID:18606302)
• VAP-A is an important regulator both of the subcellular localization of protrudin and of its ability to stimulate neurite outgrowth. (PMID:19289470)
• Protrudin-KIF5 complex contributes to the vesicular transport in neurons. (PMID:21976701)
• findings indicate that protrudin interacts with spastin and induces axon formation through its N-terminal domain. Moreover, protrudin and spastin may work together to play an indispensable role in motor axon outg (PMID:22573551)
• SPG33 protein protrudin contains hydrophobic, intramembrane hairpin domains, interacts with tubular ER proteins, and functions in ER morphogenesis by regulating the sheet-to-tubule balance and possibly the density of tubule interconnections. (PMID:23969831)
• Protrudin modulates seizure activity through GABAA receptor regulation. (PMID:31772151)
• Protrudin-mediated ER-endosome contact sites promote MT1-MMP exocytosis and cell invasion. (PMID:32479595)
• Protrudin and PDZD8 contribute to neuronal integrity by promoting lipid extraction required for endosome maturation. (PMID:32917905)
• Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS. (PMID:33154382)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfyve27	ENSDARG00000059835
mus_musculus	Zfyve27	ENSMUSG00000018820
rattus_norvegicus	Zfyve27	ENSRNOG00000014903

Protein

Protein identifiers

Protrudin — Q5T4F4 (reviewed: Q5T4F4)

Alternative names: Spastic paraplegia 33 protein, Zinc finger FYVE domain-containing protein 27

All UniProt accessions (1): Q5T4F4

UniProt curated annotations — full annotation on UniProt →

Function. Key regulator of RAB11-dependent vesicular trafficking during neurite extension through polarized membrane transport. Promotes axonal elongation and contributes to the establishment of neuronal cell polarity. Involved in nerve growth factor-induced neurite formation in VAPA-dependent manner. Contributes to both the formation and stabilization of the tubular ER network. Involved in ER morphogenesis by regulating the sheet-to-tubule balance and possibly the density of tubule interconnections. Acts as an adapter protein and facilitates the interaction of KIF5A with VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 and the ZFYVE27-KIF5A complex contributes to the transport of these proteins in neurons. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a KIF5A/B-dependent manner.

Subunit / interactions. Can form homooligomers (monomers, dimers and tetramers). Interacts with RAB11A (GDP-bound form); regulates RAB11A. Interacts with FKBP8; may negatively regulate ZFYVE27 phosphorylation. Interacts with VAPA (via MSP domain); may regulate ZFYVE27 retention in the endoplasmic reticulum and its function in cell projections formation. Interacts with VAPB (via MSP domain). Interacts with REEP1, REEP5 and ATL1. Interacts with ATL2, ATL3 and SPAST. Interacts with KIF5A and RTN3. Interacts with RAB11B (GDP-bound form), SURF4, KIF5B and KIF5C.

Subcellular location. Recycling endosome membrane. Endoplasmic reticulum membrane. Cell projection. Growth cone membrane.

Post-translational modifications. Phosphorylated. Phosphorylation is induced by NGF through the MAPK/ERK pathway and modulates interaction with RAB11A.

Isoforms (8)

UniProt ID	Names	Canonical?
Q5T4F4-1	1	yes
Q5T4F4-2	2
Q5T4F4-3	3
Q5T4F4-4	4
Q5T4F4-5	5
Q5T4F4-6	6
Q5T4F4-7	7
Q5T4F4-8	8

RefSeq proteins (46): NP_001002261, NP_001002262, NP_001167590, NP_001167591, NP_001167592, NP_001167593, NP_001372800, NP_001372804, NP_001372805, NP_001372806, NP_001372807, NP_001372808, NP_001372809, NP_001372810, NP_001372811, NP_001372812, NP_001372813, NP_001372814, NP_001372815, NP_001372816, NP_001372817, NP_001372818, NP_001372819, NP_001372820, NP_001372821, NP_001372822, NP_001372823, NP_001372824, NP_001372825, NP_001372826, NP_001372827, NP_001372828, NP_001372829, NP_001372830, NP_001372831, NP_001372832, NP_001372833, NP_001372834, NP_001372835, NP_001372837, NP_001372840, NP_001372844, NP_001372845, NP_001372847, NP_001372848, NP_653189 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000306	Znf_FYVE	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017455	Znf_FYVE-rel	Domain
IPR042405	Protrudin	Family

Pfam: PF01363

UniProt features (53 total): splice variant 9, binding site 8, region of interest 7, sequence conflict 5, strand 5, topological domain 4, sequence variant 3, mutagenesis site 3, transmembrane region 2, turn 2, chain 1, compositionally biased region 1, helix 1, intramembrane region 1, zinc finger region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1X4U	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T4F4-F1	70.16	0.17

Functional residue map

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

Ligand- & substrate-binding residues (8): 350; 353; 366; 369; 374; 377; 402; 405

Mutagenesis-validated functional residues (3):

Position	Phenotype
13	alters interaction with rab11a; when associated with a-49.
49	alters interaction with rab11a; when associated with a-13.
289	loss of interaction with vapa and loss of function in cell projections formation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 168 (showing top): PAX4_01, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_CELL_GROWTH, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_AXON_EXTENSION

GO Biological Process (6): vesicle-mediated transport (GO:0016192), neuron projection development (GO:0031175), positive regulation of axon extension (GO:0045773), neurotrophin TRK receptor signaling pathway (GO:0048011), endoplasmic reticulum tubular network formation (GO:0071787), protein localization to plasma membrane (GO:0072659)

GO Molecular Function (4): zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (15): nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), axon (GO:0030424), dendrite (GO:0030425), growth cone membrane (GO:0032584), recycling endosome membrane (GO:0055038), endoplasmic reticulum tubular network (GO:0071782), cytoplasm (GO:0005737), endosome (GO:0005768), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
cytoplasm	2
endomembrane system	2
endoplasmic reticulum subcompartment	2
neuron projection	2
plasma membrane	2
transport	1
cellular process	1
neuron development	1
plasma membrane bounded cell projection organization	1
positive regulation of cell growth	1
regulation of axon extension	1
positive regulation of developmental growth	1
axon extension	1
positive regulation of axonogenesis	1
cell surface receptor protein tyrosine kinase signaling pathway	1
neurotrophin signaling pathway	1
cellular component assembly	1
endoplasmic reticulum tubular network organization	1
protein localization to membrane	1
protein localization to cell periphery	1
transition metal ion binding	1
protein binding	1
binding	1
cation binding	1
nuclear lumen	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
dendritic tree	1
growth cone	1
endosome membrane	1
recycling endosome	1
intracellular anatomical structure	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
vacuole	1

Protein interactions and networks

STRING

1098 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFYVE27	RAB11A	P24410	992
ZFYVE27	SPAST	Q9UBP0	950
ZFYVE27	REEP1	Q9H902	915
ZFYVE27	FYCO1	Q9BQS8	880
ZFYVE27	WASHC5	Q12768	876
ZFYVE27	PDZD8	Q8NEN9	861
ZFYVE27	VAPA	Q9P0L0	818
ZFYVE27	ALDH18A1	P54886	810
ZFYVE27	KIF5A	Q12840	775
ZFYVE27	NIPA1	Q7RTP0	769
ZFYVE27	VAPB	O95292	764
ZFYVE27	ATL1	Q8WXF7	744
ZFYVE27	STARD3	Q14849	723
ZFYVE27	EXOC6	Q8TAG9	667
ZFYVE27	RAB32	Q13637	644

IntAct

94 interactions, top by confidence:

A	B	Type	Score
VAPA	ZFYVE27	psi-mi:“MI:0915”(physical association)	0.750
ZFYVE27	VAPA	psi-mi:“MI:0915”(physical association)	0.750
ZFYVE27	VAPA	psi-mi:“MI:0407”(direct interaction)	0.750
VAPA	ZFYVE27	psi-mi:“MI:0403”(colocalization)	0.750
FKBP8	ZFYVE27	psi-mi:“MI:0915”(physical association)	0.630
ZFYVE27	FKBP8	psi-mi:“MI:0915”(physical association)	0.630
TSPAN2	ZFYVE27	psi-mi:“MI:0915”(physical association)	0.560
TMEM128	ZFYVE27	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	IER3IP1	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	SLC66A2	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	GIMAP1	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	ZFYVE27	psi-mi:“MI:0915”(physical association)	0.560
STX7	ZFYVE27	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	GIMAP5	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	SACM1L	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	PIP4P2	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	TMEM14C	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	ORMDL1	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	OTOP3	psi-mi:“MI:0915”(physical association)	0.560
SLC30A8	ZFYVE27	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	TMEM243	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	TMEM65	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	RAB11A	psi-mi:“MI:0403”(colocalization)	0.560
RAB11A	ZFYVE27	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (90): SDCCAG3 (Affinity Capture-MS), ZFAND2B (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP8 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), VAPA (Affinity Capture-MS), MOSPD2 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), APOB (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), GOLGA5 (Affinity Capture-MS), ACP2 (Affinity Capture-MS), SLC7A2 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS)

ESM2 similar proteins: A6NCQ9, D2H6Z0, D2H788, D3ZBM4, D4A723, E1C2W7, P97432, P97799, Q13145, Q14596, Q3SWY0, Q3T0Y9, Q3TXX3, Q501R9, Q5F479, Q5R7K2, Q5RC94, Q5RF77, Q5T4F4, Q60943, Q60953, Q68D51, Q68EV7, Q6GND7, Q6INB3, Q6P7B7, Q6P9P8, Q80ZD7, Q80ZD8, Q810L3, Q86WK6, Q8BG47, Q8BGE4, Q8C432, Q8CEF8, Q8HYZ0, Q8IZ57, Q8JZL1, Q8N6D2, Q8N8N0

Diamond homologs: A0A0D1E015, A0JMD2, A3LX75, A4QTV1, A8QCE4, A8XJZ8, B0G126, B0WAQ0, B4JHI7, D2H5P6, D3ZVP7, D4A8G9, E1BLZ4, O13821, O14964, O95405, O96838, P0CS26, P0CS27, P34657, P40343, Q05B78, Q06651, Q0P4S0, Q0V8S0, Q0WUR5, Q13615, Q17AN2, Q2GS33, Q3TB82, Q3TXX3, Q4P7Q1, Q54CH1, Q54IL5, Q54TC3, Q5ABD9, Q5BIM5, Q5DU37, Q5PQT2, Q5R5R4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
endoplasmic reticulum organization	6	74.3×	4e-08
endoplasmic reticulum to Golgi vesicle-mediated transport	6	24.0×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	135
Likely benign	50
Benign	53

Top pathogenic / likely-pathogenic (0)

SpliceAI

2763 predictions. Top by Δscore:

Variant	Effect	Δscore
10:97744912:GCTT:G	donor_gain	1.0000
10:97744914:TT:T	donor_gain	1.0000
10:97744916:G:GG	donor_gain	1.0000
10:97748265:GTA:G	acceptor_loss	1.0000
10:97748266:TA:T	acceptor_loss	1.0000
10:97748267:A:AG	acceptor_gain	1.0000
10:97748267:AGCTT:A	acceptor_gain	1.0000
10:97748268:G:GA	acceptor_gain	1.0000
10:97748268:G:GC	acceptor_loss	1.0000
10:97748268:GCT:G	acceptor_gain	1.0000
10:97748268:GCTT:G	acceptor_gain	1.0000
10:97748268:GCTTG:G	acceptor_gain	1.0000
10:97748365:G:GG	donor_gain	1.0000
10:97750306:ACCTT:A	acceptor_gain	1.0000
10:97750307:C:G	acceptor_gain	1.0000
10:97750325:G:A	acceptor_gain	1.0000
10:97750329:A:AC	acceptor_loss	1.0000
10:97750329:A:AG	acceptor_gain	1.0000
10:97750330:G:GG	acceptor_gain	1.0000
10:97750330:GTT:G	acceptor_gain	1.0000
10:97750330:GTTGT:G	acceptor_gain	1.0000
10:97750467:GGAG:G	donor_gain	1.0000
10:97750468:GAG:G	donor_gain	1.0000
10:97750468:GAGG:G	donor_gain	1.0000
10:97750469:AGG:A	donor_loss	1.0000
10:97750470:GGT:G	donor_loss	1.0000
10:97750471:G:GG	donor_gain	1.0000
10:97750471:GTAA:G	donor_loss	1.0000
10:97750472:T:G	donor_loss	1.0000
10:97751463:G:GA	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000113211 (10:97744188 G>A,T), RS1000143813 (10:97737510 G>T), RS1000221309 (10:97743603 G>C), RS1000272279 (10:97743861 G>A), RS1000383703 (10:97735544 A>G,T), RS1000455893 (10:97749978 C>G,T), RS1000471226 (10:97746145 T>C), RS1000544350 (10:97738073 G>A), RS1000750527 (10:97736586 G>A,C,T), RS1001019050 (10:97757302 G>A), RS1001165646 (10:97739231 A>G), RS1001379650 (10:97757628 G>T), RS1001512201 (10:97738980 G>A), RS1001617163 (10:97755363 T>G), RS1001646801 (10:97755220 G>A)

Disease associations

OMIM: gene MIM:610243 | disease phenotypes: MIM:610244

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 33	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
hereditary spastic paraplegia 33	Disputed	AD

Mondo (1): hereditary spastic paraplegia 33 (MONDO:0012448)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565214	Spastic Paraplegia 33, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases expression	2
Arsenic	decreases expression, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	affects cotreatment, decreases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Acrolein	increases abundance, affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Doxorubicin	decreases expression	1
Gallic Acid	increases expression	1
Lead	affects expression, affects splicing	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Dronabinol	decreases expression	1
Urethane	increases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1
Volatile Organic Compounds	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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