NUP85

Summary

NUP85 (nucleoporin 85, HGNC:8734) is a protein-coding gene on chromosome 17q25.1, encoding Nuclear pore complex protein Nup85 (Q9BW27). Essential component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

This gene encodes a protein component of the Nup107-160 subunit of the nuclear pore complex. Nuclear pore complexes are embedded in the nuclear envelope and promote bidirectional transport of macromolecules between the cytoplasm and nucleus. The encoded protein can also bind to the C-terminus of chemokine (C-C motif) receptor 2 (CCR2) and promote chemotaxis of monocytes, thereby participating in the inflammatory response. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 79902 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome, type 17 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 223 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 49
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_024844

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8734
Approved symbol	NUP85
Name	nucleoporin 85
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	NUP75, FLJ12549
Ensembl gene	ENSG00000125450
Ensembl biotype	protein_coding
OMIM	170285
Entrez	79902

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 14 protein_coding, 6 protein_coding_CDS_not_defined, 5 nonsense_mediated_decay, 4 retained_intron

ENST00000245544, ENST00000449421, ENST00000540768, ENST00000577208, ENST00000577561, ENST00000577645, ENST00000578294, ENST00000578830, ENST00000578987, ENST00000579298, ENST00000579324, ENST00000579557, ENST00000579838, ENST00000579900, ENST00000580879, ENST00000581104, ENST00000581335, ENST00000582681, ENST00000582833, ENST00000583070, ENST00000583548, ENST00000583569, ENST00000583877, ENST00000583948, ENST00000584155, ENST00000898366, ENST00000898367, ENST00000916514, ENST00000968072

RefSeq mRNA: 3 — MANE Select: NM_024844 NM_001303276, NM_001330472, NM_024844

CCDS: CCDS32730, CCDS82202

Canonical transcript exons

ENST00000245544 — 19 exons

Exon	Start	End
ENSE00000855683	75234637	75234788
ENSE00000855684	75235100	75235201
ENSE00002726134	75205679	75205794
ENSE00003471929	75218185	75218306
ENSE00003487894	75215754	75215823
ENSE00003488671	75233058	75233158
ENSE00003498867	75231828	75231979
ENSE00003518427	75209823	75209985
ENSE00003522023	75225103	75225237
ENSE00003528082	75225342	75225464
ENSE00003553597	75231340	75231423
ENSE00003555337	75225698	75225829
ENSE00003577711	75211992	75212062
ENSE00003589899	75235578	75235758
ENSE00003601859	75213076	75213119
ENSE00003605732	75232851	75232968
ENSE00003631245	75231573	75231638
ENSE00003653331	75208527	75208620
ENSE00003787115	75226051	75226157

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.8388 / max 286.5345, expressed in 1821 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162707	32.7039	1821
162709	0.1349	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	97.51	gold quality
cerebellar cortex	UBERON:0002129	97.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.28	gold quality
cerebellum	UBERON:0002037	96.34	gold quality
right testis	UBERON:0004534	95.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.21	gold quality
tibial nerve	UBERON:0001323	95.19	gold quality
left testis	UBERON:0004533	95.15	gold quality
mucosa of transverse colon	UBERON:0004991	95.07	gold quality
right ovary	UBERON:0002118	95.04	gold quality
right uterine tube	UBERON:0001302	95.02	gold quality
oocyte	CL:0000023	94.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.84	gold quality
endocervix	UBERON:0000458	94.80	gold quality
right lobe of thyroid gland	UBERON:0001119	94.79	gold quality
lower esophagus mucosa	UBERON:0035834	94.78	gold quality
left ovary	UBERON:0002119	94.69	gold quality
body of uterus	UBERON:0009853	94.67	gold quality
ectocervix	UBERON:0012249	94.62	gold quality
granulocyte	CL:0000094	94.55	gold quality
skin of leg	UBERON:0001511	94.47	gold quality
ventricular zone	UBERON:0003053	94.41	gold quality
skin of abdomen	UBERON:0001416	94.37	gold quality
left lobe of thyroid gland	UBERON:0001120	94.33	gold quality
upper lobe of left lung	UBERON:0008952	94.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.98	gold quality
left uterine tube	UBERON:0001303	93.97	gold quality
ganglionic eminence	UBERON:0004023	93.83	gold quality
testis	UBERON:0000473	93.79	gold quality
spleen	UBERON:0002106	93.66	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.61
E-MTAB-6386	no	471.58

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• The CCL2/CCR2 pathway via FROUNT may influence the clinical severity of CHF. (PMID:17395051)
• Data show that the C Terminus of Nup120 Directly Binds Nup145C and Nup85. (PMID:19576787)
• FROUNT binds to the C-terminal domain of CCR5 in addition to that of CCR2. (PMID:19841162)
• Residues on the hydrophobic side are completely conserved among FROUNT-binding receptors. (PMID:24128342)
• results support a model of CCR2 equilibrium: chemokine binding changes the conformational equilibrium of CCR2 toward the active state, and Pro-C switches its binding partner from the membrane to FROUNT (PMID:25283965)
• the chemokine signal regulator FROUNT is identified as a target to control tumor-associated macrophages. (PMID:32001710)
• Expanding the phenotype of NUP85 mutations beyond nephrotic syndrome to primary autosomal recessive microcephaly and Seckel syndrome spectrum disorders. (PMID:34170319)
• NUP85 as a Neurodevelopmental Gene: From Podocyte to Neuron. (PMID:38136965)
• [Analysis of correlation between high expression of nucleoporin 85 (NUP85) and immune cell infiltration in hepatocellular carcinoma]. (PMID:38952090)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nup85	ENSDARG00000098679
danio_rerio	NUP85	ENSDARG00000112002
mus_musculus	Nup85	ENSMUSG00000020739
rattus_norvegicus	Nup85	ENSRNOG00000003673
drosophila_melanogaster	Nup75	FBGN0034310
caenorhabditis_elegans	npp-2	WBGENE00003788

Protein

Protein identifiers

Nuclear pore complex protein Nup85 — Q9BW27 (reviewed: Q9BW27)

Alternative names: 85 kDa nucleoporin, FROUNT, Nucleoporin Nup75, Nucleoporin Nup85, Pericentrin-1

All UniProt accessions (15): Q9BW27, F5H0W7, J3KRC0, J3KS87, J3KSH3, J3KT10, J3KTC7, J3QL49, J3QL54, J3QL91, J3QLD4, J3QLH0, J3QLV0, J3QRY3, J3QS63

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance. As part of the NPC Nup107-160 subcomplex plays a role in RNA export and in tethering NUP96/Nup98 and NUP153 to the nucleus. The Nup107-160 complex seems to be required for spindle assembly during mitosis. NUP85 is required for membrane clustering of CCL2-activated CCR2. Seems to be involved in CCR2-mediated chemotaxis of monocytes and may link activated CCR2 to the phosphatidyl-inositol 3-kinase-Rac-lammellipodium protrusion cascade. Involved in nephrogenesis.

Subunit / interactions. Component of the nuclear pore complex (NPC). Component of the NPC Nup107-160 subcomplex, consisting of at least NUP107, NUP98/Nup96, NUP160, NUP133, NUP85, NUP37, NUP43 and SEC13. Interacts with NUP160, NUP133 and SEC13. Interacts with NUP37, NUP107 and NUP43. Interacts with CCR2.

Subcellular location. Nucleus. Nuclear pore complex. Chromosome. Centromere. Kinetochore. Cytoplasm. Cytoskeleton. Spindle. Nucleus membrane.

Disease relevance. Nephrotic syndrome 17 (NPHS17) [MIM:618176] A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS17 is an autosomal recessive, steroid-resistant progressive form with onset in the first decade of life. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the nucleoporin Nup85 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BW27-1	1	yes
Q9BW27-2	2
Q9BW27-3	3

RefSeq proteins (3): NP_001290205, NP_001317401, NP_079120* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011502	Nucleoporin_Nup85	Family

Pfam: PF07575

UniProt features (12 total): splice variant 4, modified residue 3, sequence variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7R5K	ELECTRON MICROSCOPY	12
5A9Q	ELECTRON MICROSCOPY	23
7PEQ	ELECTRON MICROSCOPY	35
7R5J	ELECTRON MICROSCOPY	50

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BW27-F1	84.45	0.55

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, 92, 223

Function

Pathways and Gene Ontology

Reactome pathways

38 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-159227	Transport of the SLBP independent Mature mRNA
R-HSA-159230	Transport of the SLBP Dependant Mature mRNA
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-165054	Rev-mediated nuclear export of HIV RNA
R-HSA-168271	Transport of Ribonucleoproteins into the Host Nucleus
R-HSA-168276	NS1 Mediated Effects on Host Pathways
R-HSA-168325	Viral Messenger RNA Synthesis
R-HSA-168333	NEP/NS2 Interacts with the Cellular Export Machinery
R-HSA-170822	Regulation of Glucokinase by Glucokinase Regulatory Protein
R-HSA-180746	Nuclear import of Rev protein
R-HSA-180910	Vpr-mediated nuclear import of PICs
R-HSA-1855170	IPs transport between nucleus and cytosol
R-HSA-1855196	IP3 and IP4 transport between cytosol and nucleus
R-HSA-1855229	IP6 and IP7 transport between cytosol and nucleus
R-HSA-191859	snRNP Assembly
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-3301854	Nuclear Pore Complex (NPC) Disassembly
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-4085377	SUMOylation of SUMOylation proteins
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4615885	SUMOylation of DNA replication proteins
R-HSA-5619107	Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)
R-HSA-5663220	RHO GTPases Activate Formins

MSigDB gene sets: 366 (showing top): REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, PAL_PRMT5_TARGETS_UP, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_NUCLEAR_TRANSPORT, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION, REACTOME_HIV_INFECTION, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT

GO Biological Process (10): mRNA export from nucleus (GO:0006406), protein import into nucleus (GO:0006606), nucleocytoplasmic transport (GO:0006913), lamellipodium assembly (GO:0030032), positive regulation of DNA-templated transcription (GO:0045893), macrophage chemotaxis (GO:0048246), nephron development (GO:0072006), chemotaxis (GO:0006935), protein transport (GO:0015031), mRNA transport (GO:0051028)

GO Molecular Function (2): structural constituent of nuclear pore (GO:0017056), protein binding (GO:0005515)

GO Cellular Component (16): kinetochore (GO:0000776), nuclear envelope (GO:0005635), nuclear pore (GO:0005643), nucleoplasm (GO:0005654), spindle (GO:0005819), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), membrane (GO:0016020), nuclear pore outer ring (GO:0031080), nuclear membrane (GO:0031965), ciliary basal body (GO:0036064), chromosome, centromeric region (GO:0000775), nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
Inositol phosphate metabolism	3
Interactions of Rev with host cellular proteins	2
Influenza Infection	2
Antimicrobial mechanism of IFN-stimulated genes	1
Amplification of signal from the kinetochores	1
Transport of Mature Transcript to Cytoplasm	1
Late Phase of HIV Life Cycle	1
Influenza Viral RNA Transcription and Replication	1
Export of Viral Ribonucleoproteins from Nucleus	1
Glycolysis	1
Interactions of Vpr with host cellular proteins	1
Metabolism of non-coding RNA	1
Mitotic Anaphase	1
Mitotic Prometaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	4
cellular anatomical structure	4
nuclear pore	2
nucleus	2
nuclear envelope	2
nuclear protein-containing complex	2
RNA export from nucleus	1
gene expression	1
mRNA transport	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
nuclear transport	1
lamellipodium organization	1
plasma membrane bounded cell projection assembly	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
leukocyte chemotaxis	1
macrophage migration	1
kidney development	1
anatomical structure development	1
response to chemical	1
taxis	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
RNA transport	1
structural molecule activity	1
nucleocytoplasmic transport	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
endomembrane system	1
organelle envelope	1
nuclear lumen	1
microtubule cytoskeleton	1
cytoplasm	1
cytoskeleton	1

Protein interactions and networks

STRING

2396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUP85	NUP107	P57740	999
NUP85	SEH1L	Q96EE3	999
NUP85	NUP160	Q12769	998
NUP85	NUP133	Q8WUM0	998
NUP85	SEC13	P55735	997
NUP85	NUP43	Q8NFH3	997
NUP85	NUP37	Q8NFH4	997
NUP85	NUP98	P52948	996
NUP85	CCR2	P41597	964
NUP85	NUP88	Q99567	948
NUP85	PCNT	O95613	919
NUP85	AHCTF1	Q8WYP5	888
NUP85	NUP93	Q8N1F7	877
NUP85	CCR5	P51681	859
NUP85	NUP153	P49790	834

IntAct

132 interactions, top by confidence:

A	B	Type	Score
NUP107	NUP133	psi-mi:“MI:0914”(association)	0.930
NUP43	SEH1L	psi-mi:“MI:0915”(physical association)	0.800
NUP133	NUP85	psi-mi:“MI:0915”(physical association)	0.750
NUP133	NUP98	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NUP85	SEH1L	psi-mi:“MI:0407”(direct interaction)	0.700
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
SEC13	SEC16A	psi-mi:“MI:0914”(association)	0.640
NUP43	NUP98	psi-mi:“MI:0914”(association)	0.640
NUP85	NUP160	psi-mi:“MI:0915”(physical association)	0.590
GET4	NUP85	psi-mi:“MI:0915”(physical association)	0.560
Nup107	NUP98	psi-mi:“MI:0915”(physical association)	0.560
NUP85	CCR2	psi-mi:“MI:0407”(direct interaction)	0.560
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
VASN	AP3B1	psi-mi:“MI:0914”(association)	0.530
NUP43	KIF5B	psi-mi:“MI:0914”(association)	0.530
NUP98	NUP107	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
CD40	EXOC5	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530

BioGRID (229): NUP85 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), NUP107 (Co-fractionation), NUP85 (Co-fractionation), NUP98 (Co-fractionation), NUP85 (Affinity Capture-MS)

ESM2 similar proteins: A1A4I9, A5D796, A5PJZ5, A7S2N8, A9ULY7, B0F9L4, B2GV24, F4HQ84, F4IDS7, O60308, O75694, O75717, O94874, P32780, P37199, P59328, Q14CX7, Q1RMS6, Q28HX4, Q4R367, Q5R822, Q5RBW9, Q5ZL91, Q5ZMG1, Q66HC5, Q6DDM4, Q6NX12, Q6P3X3, Q6PGY6, Q7TQK1, Q7ZU29, Q7ZX96, Q8BGQ1, Q8BJ71, Q8BWZ3, Q8CCJ3, Q8JGR7, Q8N1F7, Q8R3N6, Q8WVM7

Diamond homologs: A1YK02, Q3ZC98, Q4QQS8, Q68FJ0, Q6DBY0, Q6DK84, Q8R480, Q9BW27

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NUP85	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 150 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
Postmitotic nuclear pore complex (NPC) reformation	13	55.2×	3e-18
Nuclear import of Rev protein	14	49.0×	2e-18
Transport of Ribonucleoproteins into the Host Nucleus	13	48.3×	2e-17
IPs transport between nucleus and cytosol	12	47.6×	2e-16
IP3 and IP4 transport between cytosol and nucleus	12	47.6×	2e-16
IP6 and IP7 transport between cytosol and nucleus	12	47.6×	2e-16
NEP/NS2 Interacts with the Cellular Export Machinery	13	46.9×	2e-17
Rev-mediated nuclear export of HIV RNA	14	46.3×	3e-18

GO biological processes:

GO term	Partners	Fold	FDR
RNA export from nucleus	6	43.2×	1e-06
nucleocytoplasmic transport	13	39.2×	5e-15
NLS-bearing protein import into nucleus	5	30.9×	9e-05
mRNA transport	8	16.2×	7e-06
protein import into nucleus	14	15.5×	1e-10
T cell proliferation	5	14.7×	2e-03
mRNA export from nucleus	6	13.7×	6e-04
protein transport	12	4.0×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	98
Likely benign	79
Benign	18

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
590317	NM_024844.5(NUP85):c.405+1G>A	Pathogenic
3769651	NM_024844.5(NUP85):c.1379G>A (p.Arg460Gln)	Likely pathogenic

SpliceAI

3786 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75205795:G:GG	donor_gain	1.0000
17:75208525:A:AG	acceptor_gain	1.0000
17:75208526:G:GA	acceptor_gain	1.0000
17:75208616:AAAAG:A	donor_loss	1.0000
17:75208618:AAG:A	donor_loss	1.0000
17:75208619:AGG:A	donor_loss	1.0000
17:75208620:GGTA:G	donor_loss	1.0000
17:75208621:G:C	donor_loss	1.0000
17:75208622:T:A	donor_loss	1.0000
17:75209810:T:TA	acceptor_gain	1.0000
17:75209814:T:TA	acceptor_gain	1.0000
17:75209815:G:A	acceptor_gain	1.0000
17:75209818:TTCA:T	acceptor_loss	1.0000
17:75209821:A:AG	acceptor_gain	1.0000
17:75209822:G:GT	acceptor_gain	1.0000
17:75209822:GA:G	acceptor_gain	1.0000
17:75209822:GAA:G	acceptor_gain	1.0000
17:75209822:GAAA:G	acceptor_gain	1.0000
17:75209822:GAAAA:G	acceptor_gain	1.0000
17:75209981:TCTCA:T	donor_gain	1.0000
17:75209982:CTCA:C	donor_gain	1.0000
17:75209983:TCA:T	donor_gain	1.0000
17:75209984:CA:C	donor_gain	1.0000
17:75209985:AG:A	donor_loss	1.0000
17:75209986:G:GG	donor_gain	1.0000
17:75209987:T:A	donor_loss	1.0000
17:75209990:G:GG	donor_gain	1.0000
17:75212063:G:GG	donor_gain	1.0000
17:75213074:A:AG	acceptor_gain	1.0000
17:75213075:G:GC	acceptor_gain	1.0000

AlphaMissense

4314 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75212005:A:C	S102R	1.000
17:75212007:T:A	S102R	1.000
17:75212007:T:G	S102R	1.000
17:75212018:G:C	R106P	1.000
17:75215784:T:A	W146R	1.000
17:75215784:T:C	W146R	1.000
17:75218214:T:A	W169R	1.000
17:75218214:T:C	W169R	1.000
17:75225752:T:A	W304R	1.000
17:75225752:T:C	W304R	1.000
17:75231375:T:C	L377P	1.000
17:75231384:T:C	L380P	1.000
17:75215779:T:C	L144P	0.999
17:75215791:T:C	L148P	0.999
17:75218206:T:C	L166P	0.999
17:75218216:G:C	W169C	0.999
17:75218216:G:T	W169C	0.999
17:75225390:T:A	W261R	0.999
17:75225390:T:C	W261R	0.999
17:75225777:T:C	L312P	0.999
17:75231359:T:A	W372R	0.999
17:75231359:T:C	W372R	0.999
17:75231387:T:C	L381P	0.999
17:75209918:T:C	S75P	0.998
17:75212006:G:T	S102I	0.998
17:75212017:C:G	R106G	0.998
17:75215793:T:C	C149R	0.998
17:75218215:G:C	W169S	0.998
17:75225392:G:C	W261C	0.998
17:75225392:G:T	W261C	0.998

dbSNP variants (sampled 300 via entrez): RS1000286168 (17:75220091 G>C), RS1000298172 (17:75206856 C>T), RS1000403465 (17:75235301 A>G), RS1000768457 (17:75230569 G>A,C), RS1000863247 (17:75230919 C>G,T), RS1000878205 (17:75218640 T>C), RS1000934200 (17:75211737 A>T), RS1001005195 (17:75225101 A>G), RS1001070799 (17:75224762 G>A,T), RS1001244553 (17:75224223 T>C), RS1001315707 (17:75210956 C>A,G), RS1001363867 (17:75231740 C>G,T), RS1001501608 (17:75206634 A>G), RS1001502403 (17:75224584 A>G), RS1001504997 (17:75205495 G>A)

Disease associations

OMIM: gene MIM:170285 | disease phenotypes: MIM:618176

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome, type 17	Strong	Autosomal recessive
familial idiopathic steroid-resistant nephrotic syndrome	Supportive	Autosomal dominant
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (3): nephrotic syndrome, type 17 (MONDO:0032580), Tourette syndrome (MONDO:0007661), familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006)

Orphanet (0):

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000347	Micrognathia
HP:0000363	Abnormal earlobe morphology
HP:0000387	Absent earlobe
HP:0000444	Convex nasal ridge
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000682	Abnormal dental enamel morphology
HP:0000707	Abnormality of the nervous system
HP:0000737	Irritability
HP:0000969	Edema
HP:0001249	Intellectual disability
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001511	Intrauterine growth retardation
HP:0001852	Sandal gap
HP:0001945	Fever
HP:0001967	Diffuse mesangial sclerosis
HP:0002027	Abdominal pain
HP:0002209	Sparse scalp hair
HP:0002315	Headache
HP:0002586	Peritonitis
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation
HP:0002907	Microscopic hematuria

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009131_22	Systemic sclerosis	2.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression, increases expression	5
bisphenol A	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
propionaldehyde	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	increases expression, increases oxidation, increases abundance, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
deguelin	decreases expression	1
K 7174	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases expression, increases oxidation, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Ozone	increases oxidation, increases abundance, affects cotreatment, increases expression	1
Paraquat	decreases expression	1
Piroxicam	decreases expression	1
Quercetin	increases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

183 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
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
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome