UBAP1

Summary

UBAP1 (ubiquitin associated protein 1, HGNC:12461) is a protein-coding gene on chromosome 9p13.3, encoding Ubiquitin-associated protein 1 (Q9NZ09). Component of the ESCRT-I complex, a regulator of vesicular trafficking process. It is a selective cancer dependency (DepMap: 88.2% of cell lines).

This gene is a member of the UBA domain family, whose members include proteins having connections to ubiquitin and the ubiquitination pathway. The ubiquitin associated domain is thought to be a non-covalent ubiquitin binding domain consisting of a compact three helix bundle. This particular protein originates from a gene locus in a refined region on chromosome 9 undergoing loss of heterozygosity in nasopharyngeal carcinoma (NPC). Taking into account its cytogenetic location, this UBA domain family member is being studies as a putative target for mutation in nasopharyngeal carcinomas. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 51271 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spastic paraplegia 80, autosomal dominant (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 130 total — 12 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 39
• Cancer dependency (DepMap): dependent in 88.2% of screened cell lines
• MANE Select transcript: NM_016525

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12461
Approved symbol	UBAP1
Name	ubiquitin associated protein 1
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165006
Ensembl biotype	protein_coding
OMIM	609787
Entrez	51271

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 41 protein_coding

ENST00000297661, ENST00000359544, ENST00000379186, ENST00000625521, ENST00000626262, ENST00000859530, ENST00000859531, ENST00000859532, ENST00000859533, ENST00000859534, ENST00000859535, ENST00000859536, ENST00000859537, ENST00000859538, ENST00000859539, ENST00000859540, ENST00000859541, ENST00000859542, ENST00000859543, ENST00000859544, ENST00000859545, ENST00000859546, ENST00000859547, ENST00000859548, ENST00000859549, ENST00000859550, ENST00000859551, ENST00000859552, ENST00000940196, ENST00000940197, ENST00000940198, ENST00000940199, ENST00000965871, ENST00000965872, ENST00000965873, ENST00000965874, ENST00000965875, ENST00000965876, ENST00000965877, ENST00000965878, ENST00000965879

RefSeq mRNA: 5 — MANE Select: NM_016525 NM_001171201, NM_001171202, NM_001171203, NM_001171204, NM_016525

CCDS: CCDS55303, CCDS6550

Canonical transcript exons

ENST00000297661 — 7 exons

Exon	Start	End
ENSE00001089268	34241185	34242108
ENSE00001089269	34250658	34250759
ENSE00001089270	34234216	34234340
ENSE00001089271	34249779	34249961
ENSE00001429404	34179043	34179240
ENSE00001564674	34251392	34252523
ENSE00003577215	34220908	34220948

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 97.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.1824 / max 1085.8611, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96496	54.1824	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.22	gold quality
gastrocnemius	UBERON:0001388	96.17	gold quality
muscle of leg	UBERON:0001383	95.61	gold quality
right adrenal gland cortex	UBERON:0035827	95.05	gold quality
left adrenal gland	UBERON:0001234	94.90	gold quality
esophagus mucosa	UBERON:0002469	94.84	gold quality
right adrenal gland	UBERON:0001233	94.83	gold quality
left adrenal gland cortex	UBERON:0035825	94.60	gold quality
esophagus	UBERON:0001043	94.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.42	gold quality
lower esophagus	UBERON:0013473	94.07	gold quality
islet of Langerhans	UBERON:0000006	94.06	gold quality
ventricular zone	UBERON:0003053	94.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.05	gold quality
ectocervix	UBERON:0012249	94.00	gold quality
adrenal cortex	UBERON:0001235	93.98	gold quality
adrenal gland	UBERON:0002369	93.86	gold quality
blood	UBERON:0000178	93.70	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.66	gold quality
popliteal artery	UBERON:0002250	93.63	gold quality
tibial artery	UBERON:0007610	93.63	gold quality
vagina	UBERON:0000996	93.51	gold quality
muscle organ	UBERON:0001630	93.45	gold quality
skeletal muscle organ	UBERON:0014892	93.45	gold quality
anterior cingulate cortex	UBERON:0009835	93.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.13	gold quality
stromal cell of endometrium	CL:0002255	93.12	gold quality
cingulate cortex	UBERON:0003027	93.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.96	gold quality
right frontal lobe	UBERON:0002810	92.91	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.15
E-MTAB-8060	no	179.04
E-MTAB-7303	no	107.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting UBAP1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 88.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 15)

• the identification of differential expression patterns of ubap1 in different tumors. (PMID:12451983)
• Decreased expression of UBAP1 protein is a possible point of dysfunction along the pathogenesis pathway for nasopharyngeal carcinoma that may contribute to malignant transformation. (PMID:16226037)
• Our data for the first time identifies UBAP1 as a genetic risk factor for FTLD and suggests a mechanistic relationship between this protein and TDP-43. (PMID:19217189)
• The upregulation of ubap1 gene expression mainly and the downregulation of p16 gene expression mainly may simultaneously participate in the pathogenesis of acute leukemia. (PMID:21129243)
• The biochemical specificity in ESCRT-I assembly is matched by functional specialisation as siRNA-mediated depletion of UBAP1 (PMID:24284069)
• Results present crystal structures of the coiled-coil domain of the HD-PTP phosphatase and its complex with UBAP1. The coiled-coil domain adopts an unexpected open and rigid conformation. The HD-PTP:UBAP1 structure identifies the molecular determinants of the interaction and provides a molecular basis for the specific functional cooperation between HD-PTP and UBAP1. (PMID:27839950)
• Combined targeting of UBAP1 and toll-like receptor adaptors TIRAP and MyD88 by Pseudomonas aeruginosa PumA impedes both cytokine and toll-like receptor signalling, highlighting a novel strategy for innate immune evasion. (PMID:28483816)
• UBAP1 links endosomal trafficking to the ubiquitination machinery pathways that have been previously implicated in Hereditary Spastic Paraplegia (PMID:30929741)
• mRNA in the fibroblasts of individuals with pathological truncating variants in UBAP1 escapes nonsense-mediated decay and thus leads to the expression of truncated proteins. In addition, concentrations of the full-length protein are reduced in comparison to those in controls. This suggests either a dominant-negative effect or haploinsufficiency. (PMID:30929741)
• Our study provides genetic and biochemical evidence that mutations in UBAP1 can cause pure autosomal dominant spastic paraplegia. (PMID:31203368)
• The full-length UBAP1 protein is involved in endosomal dynamics in neurons, while loss of UBAP1 function may perturb endosomal fusion and sorting of ubiquitinated cargos. These effects could be more prominent in neurons, thereby giving rise to the phenotype of a neurodegenerative disease such as hereditary spastic paraplegia. (PMID:31515522)
• Truncating variants in UBAP1 associated with childhood-onset nonsyndromic hereditary spastic paraplegia. (PMID:31696996)
• Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project. (PMID:32934340)
• Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia. (PMID:34191852)
• A novel UBAP1 truncated variant in a Chinese family with hereditary spastic paraplegia. (PMID:35347897)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubap1	ENSDARG00000058746
mus_musculus	Ubap1	ENSMUSG00000028437
rattus_norvegicus	Ubap1	ENSRNOG00000012004
drosophila_melanogaster	CG10435	FBGN0037539

Paralogs (1): UBAP1L (ENSG00000246922)

Protein

Protein identifiers

Ubiquitin-associated protein 1 — Q9NZ09 (reviewed: Q9NZ09)

Alternative names: Nasopharyngeal carcinoma-associated gene 20 protein

All UniProt accessions (3): A0A0D9SG79, A0A6G6AA68, Q9NZ09

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Plays a role in the proteasomal degradation of ubiquitinated cell-surface proteins, such as EGFR and BST2.

Subunit / interactions. Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoichiometry. Interacts with PTPN23. Interacts (via UBA domains) with ubiquitinated proteins.

Subcellular location. Cytoplasm. Cytosol. Endosome.

Tissue specificity. Ubiquitous. Highly expressed in heart, brain, placenta, lung, liver, skeletal muscle and pancreas.

Disease relevance. Spastic paraplegia 80, autosomal dominant (SPG80) [MIM:618418] 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The UMA domain mediates association with the ESCRT-I complex.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NZ09-1	1	yes
Q9NZ09-2	2
Q9NZ09-3	3
Q9NZ09-4	4

RefSeq proteins (5): NP_001164672, NP_001164673, NP_001164674, NP_001164675, NP_057609* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009060	UBA-like_sf	Homologous_superfamily
IPR015940	UBA	Domain
IPR023340	UMA	Domain
IPR038870	UBAP1	Family
IPR042575	UBAP1_C	Homologous_superfamily
IPR049467	UBAP-1-like_UBA2	Domain

Pfam: PF21267, PF22567

UniProt features (42 total): mutagenesis site 9, helix 9, sequence conflict 5, domain 3, modified residue 3, splice variant 3, sequence variant 3, region of interest 3, compositionally biased region 2, chain 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4AE4	X-RAY DIFFRACTION	1.65
5LM1	X-RAY DIFFRACTION	2.55
1WGN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZ09-F1	63.60	0.20

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): 205, 289, 146

Mutagenesis-validated functional residues (9):

Position	Phenotype
17–19	abolishes association with the escrt-i complex.
20–22	abolishes association with the escrt-i complex.
37	abolishes association with the escrt-i complex.
59	abolishes association with the escrt-i complex.
268	abolished interaction with ptpn23.
269	does not affect interaction with ptpn23.
271	does not affect interaction with ptpn23.
404	strongly reduced interaction with ubiquitinated proteins.
472	strongly reduced interaction with ubiquitinated proteins.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-162588	Budding and maturation of HIV virion
R-HSA-174490	Membrane binding and targetting of GAG proteins
R-HSA-917729	Endosomal Sorting Complex Required For Transport (ESCRT)
R-HSA-9610379	HCMV Late Events
R-HSA-9615710	Late endosomal microautophagy

MSigDB gene sets: 263 (showing top): REACTOME_ENDOSOMAL_SORTING_COMPLEX_REQUIRED_FOR_TRANSPORT_ESCRT, WANG_CLIM2_TARGETS_UP, GOBP_ENDOSOME_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_VESICLE_ORGANIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_VACUOLAR_TRANSPORT, CREBP1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, REACTOME_HIV_INFECTION

GO Biological Process (5): multivesicular body assembly (GO:0036258), ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043162), protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043328), membrane fission (GO:0090148), protein transport (GO:0015031)

GO Molecular Function (2): ubiquitin binding (GO:0043130), protein binding (GO:0005515)

GO Cellular Component (6): ESCRT I complex (GO:0000813), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Late Phase of HIV Life Cycle	1
Synthesis And Processing Of GAG, GAGPOL Polyproteins	1
Membrane Trafficking	1
HCMV Infection	1
Autophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
multivesicular body organization	1
organelle assembly	1
ubiquitin-dependent protein catabolic process	1
protein catabolic process in the vacuole	1
multivesicular body sorting pathway	1
intracellular protein transport	1
late endosome to vacuole transport via multivesicular body sorting pathway	1
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	1
protein localization to vacuole	1
establishment of protein localization to vacuole	1
membrane organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
ubiquitin-like protein binding	1
binding	1
endosome membrane	1
ESCRT complex	1
membrane protein complex	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBAP1	VPS28	Q9UK41	993
UBAP1	TSG101	Q99816	986
UBAP1	VPS37A	Q8NEZ2	949
UBAP1	PTPN23	Q9H3S7	843
UBAP1	MVB12A	Q96EY5	776
UBAP1	CHMP4A	Q9BY43	722
UBAP1	MVB12B	Q9H7P6	680
UBAP1	CHMP5	Q9NZZ3	666
UBAP1	VPS37C	A5D8V6	664
UBAP1	VPS36	Q86VN1	654
UBAP1	VPS37D	Q86XT2	583
UBAP1	CHMP6	Q96FZ7	576
UBAP1	CHMP1A	Q9HD42	557
UBAP1	VPS25	Q9BRG1	548
UBAP1	VPS37B	Q9H9H4	537

IntAct

16 interactions, top by confidence:

A	B	Type	Score
TSG101	VPS37C	psi-mi:“MI:0914”(association)	0.780
VPS28	VPS37A	psi-mi:“MI:0914”(association)	0.640
UBAP1	PPIC	psi-mi:“MI:0915”(physical association)	0.560
BQRF1	UBAP1	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
CUL4B	GGTLC3	psi-mi:“MI:0914”(association)	0.350
VPS28	MVB12A	psi-mi:“MI:0914”(association)	0.350
NEU4	AIP	psi-mi:“MI:0914”(association)	0.350
VPS28	PRPF6	psi-mi:“MI:0914”(association)	0.350
UBAP1	VPS37A	psi-mi:“MI:0914”(association)	0.350
VPS28	DCAF6	psi-mi:“MI:0914”(association)	0.350
Map3k1	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (88): UBAP1 (Two-hybrid), UBAP1 (Affinity Capture-RNA), UBAP1 (Affinity Capture-RNA), UBAP1 (Affinity Capture-RNA), UBAP1 (Affinity Capture-RNA), UBAP1 (Reconstituted Complex), UBAP1 (Biochemical Activity), UBAP1 (Affinity Capture-MS), UBAP1 (Co-fractionation), UBAP1 (Two-hybrid), UBAP1 (Affinity Capture-Western), UBAP1 (Affinity Capture-MS), UBAP1 (Affinity Capture-MS), UBAP1 (Affinity Capture-MS), UBAP1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8GUX5, A2AIW0, D3ZQL6, E9Q0S6, F6P6X0, O35261, O54943, P53564, P56931, P59729, Q08E13, Q16254, Q1LVK9, Q3UH68, Q3ULZ2, Q5HZN1, Q5SSZ5, Q5XIS7, Q61194, Q68CZ2, Q6A037, Q6PCQ0, Q6PD31, Q6ZUJ8, Q76LL6, Q7TN02, Q7YR76, Q80XI3, Q80Z38, Q8BGT6, Q8BH48, Q8C5R2, Q8IZQ8, Q8K298, Q8K382, Q8K4J6, Q8R2H7, Q8R5I7, Q8VIM5, Q90YL3

Diamond homologs: F5GYI3, Q5XIS7, Q8BH48, Q9NZ09, F6P6X0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UBAP1	“form complex”	“ESCRT-I complex, VPS37A-UBAP1 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Budding and maturation of HIV virion	5	169.9×	1e-09
Endosomal Sorting Complex Required For Transport (ESCRT)	5	153.5×	2e-09
Late endosomal microautophagy	5	135.9×	2e-09
HCMV Late Events	5	41.0×	8e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	5	376.2×	6e-11
viral budding via host ESCRT complex	5	286.6×	1e-10
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	5	194.2×	6e-10
multivesicular body assembly	5	188.1×	6e-10
membrane fission	5	146.8×	2e-09
macroautophagy	5	86.0×	3e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	8
Uncertain significance	71
Likely benign	7
Benign	7

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
1686288	NM_016525.5(UBAP1):c.293del (p.Gly98fs)	Pathogenic
2500178	NM_016525.5(UBAP1):c.476_477del (p.Asp158_Phe159insTer)	Pathogenic
4541426	NM_016525.5(UBAP1):c.324_325del (p.His108fs)	Pathogenic
627551	NM_016525.5(UBAP1):c.436_437insTGAG (p.Ser146fs)	Pathogenic
627552	NM_016525.5(UBAP1):c.426_427del (p.Lys143fs)	Pathogenic
627553	NM_016525.5(UBAP1):c.373C>T (p.Gln125Ter)	Pathogenic
627554	NM_016525.5(UBAP1):c.286_290dup (p.Glu97fs)	Pathogenic
627555	NM_016525.5(UBAP1):c.295dup (p.Asp99fs)	Pathogenic
627556	NM_016525.5(UBAP1):c.361dup (p.Leu121fs)	Pathogenic
689455	NM_016525.5(UBAP1):c.247_248insGTGAATTC (p.Ile83fs)	Pathogenic
689456	NM_016525.5(UBAP1):c.526G>T (p.Glu176Ter)	Pathogenic
827821	NM_016525.5(UBAP1):c.316A>T (p.Lys106Ter)	Pathogenic
1679276	NM_016525.5(UBAP1):c.1265A>G (p.Gln422Arg)	Likely pathogenic
3338070	NM_016525.5(UBAP1):c.478_482dup (p.Cys161fs)	Likely pathogenic
3362862	NM_016525.5(UBAP1):c.487G>T (p.Glu163Ter)	Likely pathogenic
3900660	NM_016525.5(UBAP1):c.429dup (p.Val144fs)	Likely pathogenic
4076285	NM_016525.5(UBAP1):c.768del (p.Ile257fs)	Likely pathogenic
4077726	NM_016525.5(UBAP1):c.-20C>T	Likely pathogenic
4077727	NM_001171201.1(UBAP1):c.19G>T (p.Gly7Ter)	Likely pathogenic
4813691	NM_016525.5(UBAP1):c.478G>T (p.Glu160Ter)	Likely pathogenic

SpliceAI

1552 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34179238:CAGGT:C	donor_loss	1.0000
9:34179239:AGGT:A	donor_loss	1.0000
9:34179241:GTGAG:G	donor_loss	1.0000
9:34203947:G:GT	donor_gain	1.0000
9:34234211:TATA:T	acceptor_loss	1.0000
9:34234212:ATAG:A	acceptor_gain	1.0000
9:34234212:ATAGG:A	acceptor_gain	1.0000
9:34234213:TAG:T	acceptor_loss	1.0000
9:34234214:A:AG	acceptor_gain	1.0000
9:34234214:AG:A	acceptor_gain	1.0000
9:34234214:AGG:A	acceptor_gain	1.0000
9:34234215:G:GG	acceptor_gain	1.0000
9:34234215:G:GT	acceptor_loss	1.0000
9:34234215:GG:G	acceptor_gain	1.0000
9:34234215:GGG:G	acceptor_gain	1.0000
9:34234338:CAGG:C	donor_loss	1.0000
9:34234339:AGGT:A	donor_loss	1.0000
9:34234340:GGTA:G	donor_loss	1.0000
9:34234342:T:G	donor_loss	1.0000
9:34241183:A:AG	acceptor_gain	1.0000
9:34241184:G:GG	acceptor_gain	1.0000
9:34246992:G:GT	donor_gain	1.0000
9:34249946:A:T	donor_gain	1.0000
9:34249958:GCAG:G	donor_gain	1.0000
9:34249959:CAG:C	donor_loss	1.0000
9:34249961:GGTG:G	donor_loss	1.0000
9:34249962:GTGA:G	donor_loss	1.0000
9:34250655:TA:T	acceptor_loss	1.0000
9:34250656:A:AG	acceptor_gain	1.0000
9:34250657:G:GA	acceptor_gain	1.0000

AlphaMissense

3346 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34251437:T:C	F472L	0.997
9:34251439:T:A	F472L	0.997
9:34251439:T:G	F472L	0.997
9:34251507:T:C	L495P	0.997
9:34251438:T:C	F472S	0.995
9:34241521:T:C	F166L	0.993
9:34241523:T:A	F166L	0.993
9:34241523:T:G	F166L	0.993
9:34250671:T:C	L427P	0.993
9:34241564:T:C	L180P	0.992
9:34241202:A:C	E59D	0.990
9:34241202:A:T	E59D	0.990
9:34251423:T:C	F467S	0.989
9:34251495:C:A	A491D	0.989
9:34251507:T:A	L495H	0.989
9:34251405:T:C	L461P	0.988
9:34251465:T:C	L481S	0.987
9:34251494:G:C	A491P	0.986
9:34241537:T:C	L171S	0.985
9:34249929:G:C	A412P	0.980
9:34241827:T:C	F268L	0.979
9:34241829:C:A	F268L	0.979
9:34241829:C:G	F268L	0.979
9:34251434:G:C	G471R	0.979
9:34251465:T:G	L481W	0.979
9:34251516:G:C	R498P	0.979
9:34241414:T:C	L130P	0.978
9:34241522:T:G	F166C	0.978
9:34234263:T:C	F28L	0.977
9:34234265:C:A	F28L	0.977

dbSNP variants (sampled 300 via entrez): RS1000027985 (9:34194191 G>A), RS1000039685 (9:34193361 G>A,T), RS1000069003 (9:34187153 C>T), RS1000077245 (9:34187718 T>A), RS1000084297 (9:34234570 C>T), RS1000140901 (9:34240854 T>C), RS1000214722 (9:34240476 A>G,T), RS1000336686 (9:34187570 A>T), RS1000365216 (9:34205094 G>T), RS1000394102 (9:34181967 A>T), RS1000408158 (9:34205817 C>A,T), RS1000502545 (9:34230624 A>G), RS1000527321 (9:34198571 G>A), RS1000532097 (9:34242529 C>A), RS1000539776 (9:34234768 G>A)

Disease associations

OMIM: gene MIM:609787 | disease phenotypes: MIM:618418, MIM:303350

GenCC curated gene-disease

Disease	Classification	Inheritance
spastic paraplegia 80, autosomal dominant	Strong	Autosomal dominant
hereditary spastic paraplegia 12	Supportive	Autosomal dominant
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (4): spastic paraplegia 80, autosomal dominant (MONDO:0032737), hereditary spastic paraplegia (MONDO:0019064), Tourette syndrome (MONDO:0007661), hereditary spastic paraplegia 12 (MONDO:0011489)

Orphanet (2): Autosomal dominant spastic paraplegia type 80 (Orphanet:631068), Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000605	Supranuclear gaze palsy
HP:0000640	Gaze-evoked nystagmus
HP:0000641	Dysmetric saccades
HP:0001250	Seizure
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001288	Gait disturbance
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001761	Pes cavus
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait
HP:0002067	Bradykinesia
HP:0002070	Limb ataxia
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002169	Clonus
HP:0002314	Degeneration of the lateral corticospinal tracts
HP:0002395	Lower limb hyperreflexia
HP:0002607	Bowel incontinence
HP:0002921	Abnormal cerebrospinal fluid morphology
HP:0003394	Muscle spasm
HP:0003457	EMG abnormality
HP:0003487	Babinski sign
HP:0003621	Juvenile onset
HP:0006986	Upper limb spasticity
HP:0007020	Progressive spastic paraplegia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006014_14	Creatine kinase levels	3.000000e-08
GCST006626_7	Pulse pressure	8.000000e-13
GCST010136_34	Fruit consumption	4.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004534	creatine kinase measurement
EFO:0005763	pulse pressure measurement
EFO:0008111	diet measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
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
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850
C537484	Spastic paraplegia 12, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	affects expression, increases reaction, affects cotreatment, increases abundance, increases expression	3
Vehicle Emissions	increases abundance, increases expression, affects expression, increases reaction	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Valproic Acid	affects expression, decreases expression	2
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
testosterone undecanoate	affects cotreatment, decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
PCI 5002	increases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Caffeine	decreases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Indomethacin	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Thiram	increases expression	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome