VPS16

Summary

VPS16 (VPS16 core subunit of CORVET and HOPS complexes, HGNC:14584) is a protein-coding gene on chromosome 20p13, encoding Vacuolar protein sorting-associated protein 16 homolog (Q9H269). Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. It is a selective cancer dependency (DepMap: 28.3% of cell lines).

Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps16 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 64601 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dystonia 30 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 195 total — 10 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 22
• Cancer dependency (DepMap): dependent in 28.3% of screened cell lines
• MANE Select transcript: NM_022575

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14584
Approved symbol	VPS16
Name	VPS16 core subunit of CORVET and HOPS complexes
Location	20p13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000215305
Ensembl biotype	protein_coding
OMIM	608550
Entrez	64601

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000380443, ENST00000380445, ENST00000380469, ENST00000417508, ENST00000453689, ENST00000466415, ENST00000481812, ENST00000487461, ENST00000876977, ENST00000876978, ENST00000876979, ENST00000876980, ENST00000940250, ENST00000967587, ENST00000967588, ENST00000967589, ENST00000967590, ENST00000967591, ENST00000967592, ENST00000967593, ENST00000967594, ENST00000967595

RefSeq mRNA: 2 — MANE Select: NM_022575 NM_022575, NM_080413

CCDS: CCDS13036, CCDS13037

Canonical transcript exons

ENST00000380445 — 24 exons

Exon	Start	End
ENSE00000656599	2860449	2860593
ENSE00000656601	2860748	2860863
ENSE00000858686	2860054	2860151
ENSE00000858687	2860239	2860367
ENSE00001613102	2865399	2865495
ENSE00001643831	2862579	2862710
ENSE00001667065	2864179	2864287
ENSE00001760062	2866212	2866315
ENSE00002244006	2862054	2862130
ENSE00003461750	2861805	2861899
ENSE00003476275	2861225	2861280
ENSE00003487292	2864547	2864654
ENSE00003508715	2864365	2864462
ENSE00003527192	2866430	2866732
ENSE00003590083	2861615	2861704
ENSE00003598317	2864978	2865055
ENSE00003633529	2863065	2863100
ENSE00003638062	2863949	2864083
ENSE00003638404	2860970	2861092
ENSE00003652371	2863290	2863398
ENSE00003660842	2862807	2862934
ENSE00003662004	2865148	2865317
ENSE00003690383	2859719	2859807
ENSE00003844557	2840745	2840827

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 96.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.9274 / max 70.2164, expressed in 1814 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183188	11.7714	1803
183187	5.1560	1743

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.80	gold quality
cerebellar hemisphere	UBERON:0002245	94.38	gold quality
cerebellar cortex	UBERON:0002129	94.30	gold quality
right lobe of thyroid gland	UBERON:0001119	94.07	gold quality
left lobe of thyroid gland	UBERON:0001120	93.75	gold quality
body of uterus	UBERON:0009853	93.34	gold quality
cerebellum	UBERON:0002037	93.28	gold quality
right ovary	UBERON:0002118	93.08	gold quality
thyroid gland	UBERON:0002046	93.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.93	gold quality
endocervix	UBERON:0000458	92.88	gold quality
spleen	UBERON:0002106	92.87	gold quality
body of pancreas	UBERON:0001150	92.77	gold quality
ectocervix	UBERON:0012249	92.68	gold quality
left ovary	UBERON:0002119	92.51	gold quality
middle temporal gyrus	UBERON:0002771	92.32	gold quality
adenohypophysis	UBERON:0002196	92.21	gold quality
right frontal lobe	UBERON:0002810	92.20	gold quality
body of stomach	UBERON:0001161	92.17	gold quality
mucosa of transverse colon	UBERON:0004991	92.13	gold quality
left uterine tube	UBERON:0001303	92.02	gold quality
right uterine tube	UBERON:0001302	91.96	gold quality
stromal cell of endometrium	CL:0002255	91.90	gold quality
lower esophagus mucosa	UBERON:0035834	91.88	gold quality
monocyte	CL:0000576	91.79	gold quality
upper lobe of left lung	UBERON:0008952	91.69	gold quality
omental fat pad	UBERON:0010414	91.65	gold quality
peritoneum	UBERON:0002358	91.63	gold quality
transverse colon	UBERON:0001157	91.60	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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 28.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• HOPS subunit Vps16 recruits Vps33A to the human HOPS complex; residues 642-736 are necessary and sufficient for this interaction. (PMID:23901104)
• VPS16 is a new causative gene for adolescent-onset primary dystonia. (PMID:27174565)
• Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities. (PMID:32808683)
• Mutation screening of VPS16 gene in patients with isolated dystonia. (PMID:33482438)
• Mutations in the VPS16 Gene in 56 Early-Onset Dystonia Patients. (PMID:33595841)
• Bi-allelic VPS16 variants limit HOPS/CORVET levels and cause a mucopolysaccharidosis-like disease. (PMID:33938619)
• A Recurrent VPS16 p.Arg187* Nonsense Variant in Early-Onset Generalized Dystonia. (PMID:33998058)
• Homozygous missense VPS16 variant is associated with a novel disease, resembling mucopolysaccharidosis-plus syndrome in two siblings. (PMID:34013567)
• Overexpression of VPS16 correlates with tumor progression and chemoresistance in colorectal cancer. (PMID:35367832)
• Bioinformatics Analysis of the Prognostic Significance of VPS16 in Hepatocellular Carcinoma and Its Role in Drug Screening. (PMID:37124933)
• Dominant VPS16 Pathogenic Variants: Not Only Isolated Dystonia. (PMID:38291845)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vps16	ENSDARG00000059902
mus_musculus	Vps16	ENSMUSG00000027411
rattus_norvegicus	Vps16	ENSRNOG00000021222
drosophila_melanogaster	Vps16A	FBGN0285911
caenorhabditis_elegans		WBGENE00006516

Protein

Protein identifiers

Vacuolar protein sorting-associated protein 16 homolog — Q9H269 (reviewed: Q9H269)

All UniProt accessions (3): Q9H269, Q5JUA9, Q5JUB0

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations. Required for recruitment of VPS33A to the HOPS complex. Required for fusion of endosomes and autophagosomes with lysosomes; the function is dependent on its association with VPS33A but not VPS33B. The function in autophagosome-lysosome fusion implicates STX17 but not UVRAG.

Subunit / interactions. Core component of at least two putative endosomal tethering complexes, the homotypic fusion and vacuole protein sorting (HOPS) complex and the class C core vacuole/endosome tethering (CORVET) complex. Their common core is composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, which in HOPS further associates with VPS39 and VPS41 and in CORVET with VPS8 and TGFBRAP1. Interacts with RAB5C. Interacts with STX17, MON1B. Associates with adapter protein complex 3 (AP-3) and clathrin:AP-3 complexes.

Subcellular location. Late endosome membrane. Lysosome membrane. Early endosome. Cytoplasmic vesicle. Clathrin-coated vesicle. Autophagosome.

Tissue specificity. Ubiquitous.

Disease relevance. Dystonia 30 (DYT30) [MIM:619291] A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT30 is characterized by early onset and predominantly cervical, bulbar, orofacial, and upper limb involvement. Some patients have a more complex phenotype with neurocognitive impairment, including mild intellectual disability or psychiatric manifestations. Loss of ambulation is observed in some cases. DYT30 inheritance is autosomal dominant with incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry. The transmission pattern of DYT30 in most families is consistent with autosomal dominant inheritance. However, a homozygous VPS16 variant has been found in a multigenerational consanguineous family with autosomal recessive inheritance of DYT30.

Similarity. Belongs to the VPS16 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H269-1	1	yes
Q9H269-2	2

RefSeq proteins (2): NP_072097, NP_536338 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006925	Vps16_C	Domain
IPR006926	Vps16_N	Domain
IPR016534	VPS16	Family
IPR038132	Vps16_C_sf	Homologous_superfamily

Pfam: PF04840, PF04841

UniProt features (21 total): sequence conflict 5, helix 5, sequence variant 5, mutagenesis site 2, chain 1, region of interest 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4BX9	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H269-F1	91.35	0.72

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 (1): 4

Mutagenesis-validated functional residues (2):

Position	Phenotype
725	disrupts interaction with vps33a, no effect on interaction with vps18 and impairs endosome-lysosome fusion; when associa
669	disrupts interaction with vps33a, no effect on interaction with vps18 and impairs endosome-lysosome fusion; when associa

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9754560	SARS-CoV-2 modulates autophagy

MSigDB gene sets: 210 (showing top): RNGTGGGC_UNKNOWN, GOBP_LYSOSOMAL_TRANSPORT, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, BIOCARTA_SRCRPTP_PATHWAY, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_MEMBRANE_FUSION, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, GOBP_MACROAUTOPHAGY, GGAANCGGAANY_UNKNOWN

GO Biological Process (10): intracellular protein transport (GO:0006886), endosome to lysosome transport (GO:0008333), endosomal transport (GO:0016197), endosomal vesicle fusion (GO:0034058), regulation of SNARE complex assembly (GO:0035542), vacuole fusion, non-autophagic (GO:0042144), autophagosome maturation (GO:0097352), autophagy (GO:0006914), vacuole organization (GO:0007033), protein transport (GO:0015031)

GO Molecular Function (3): actin binding (GO:0003779), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (19): lysosome (GO:0005764), lysosomal membrane (GO:0005765), endosome (GO:0005768), early endosome (GO:0005769), late endosome (GO:0005770), autophagosome (GO:0005776), endosome membrane (GO:0010008), clathrin-coated vesicle (GO:0030136), axon (GO:0030424), HOPS complex (GO:0030897), late endosome membrane (GO:0031902), CORVET complex (GO:0033263), neuronal cell body (GO:0043025), recycling endosome (GO:0055037), presynapse (GO:0098793), cytoplasm (GO:0005737), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), vesicle tethering complex (GO:0099023)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endosome	5
cellular anatomical structure	3
intracellular protein localization	2
intracellular transport	2
vesicle-mediated transport	2
vesicle tethering complex	2
protein transport	1
lysosomal transport	1
intercellular transport	1
vesicle fusion	1
SNARE complex assembly	1
regulation of protein-containing complex assembly	1
vacuole fusion	1
macroautophagy	1
protein-containing complex disassembly	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
organelle organization	1
transport	1
establishment of protein localization	1
cytoskeletal protein binding	1
actin binding	1
protein-containing complex binding	1
binding	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
endomembrane system	1
cytoplasmic vesicle	1
vacuole	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
coated vesicle	1
neuron projection	1
membrane protein complex	1
late endosome	1
endosome membrane	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

1486 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS16	VPS39	Q96JC1	999
VPS16	VPS18	Q9P253	998
VPS16	VPS11	Q9H270	998
VPS16	VPS33A	Q96AX1	997
VPS16	VPS41	P49754	974
VPS16	VPS8	Q8N3P4	970
VPS16	TGFBRAP1	Q8WUH2	947
VPS16	UVRAG	Q9P2Y5	938
VPS16	VPS45	Q9NRW7	853
VPS16	STX17	P56962	837
VPS16	VIPAS39	Q9H9C1	709
VPS16	CCZ1B	P86790	706
VPS16	VPS33B	Q9H267	674
VPS16	VAMP8	Q9BV40	642
VPS16	VTI1B	Q9UEU0	626

IntAct

142 interactions, top by confidence:

A	B	Type	Score
VPS16	VPS33A	psi-mi:“MI:0914”(association)	0.950
VPS33A	VPS16	psi-mi:“MI:0915”(physical association)	0.950
VPS16	VPS33A	psi-mi:“MI:0915”(physical association)	0.950
VPS16	VPS33A	psi-mi:“MI:0407”(direct interaction)	0.950
VPS33A	VPS16	psi-mi:“MI:0407”(direct interaction)	0.950
VPS18	VPS16	psi-mi:“MI:0914”(association)	0.840
VPS18	VPS16	psi-mi:“MI:0915”(physical association)	0.840
VPS16	VPS18	psi-mi:“MI:0915”(physical association)	0.840
VPS11	VPS16	psi-mi:“MI:0914”(association)	0.800
VPS16	VPS11	psi-mi:“MI:0914”(association)	0.800
VPS16	VPS11	psi-mi:“MI:0915”(physical association)	0.800
TGFBRAP1	VPS16	psi-mi:“MI:0915”(physical association)	0.800
VPS11	VPS41	psi-mi:“MI:0914”(association)	0.710
VPS16	VPS41	psi-mi:“MI:0914”(association)	0.640
VPS16	STX17	psi-mi:“MI:0915”(physical association)	0.540
STX17	VPS33A	psi-mi:“MI:0914”(association)	0.540
STX17	VPS16	psi-mi:“MI:0403”(colocalization)	0.540
CT55	BLTP3B	psi-mi:“MI:0914”(association)	0.530

BioGRID (204): VPS16 (Affinity Capture-MS), VPS16 (Affinity Capture-MS), VPS16 (Affinity Capture-MS), VPS16 (Reconstituted Complex), VPS16 (Reconstituted Complex), PSMB6 (Co-fractionation), VPS16 (Affinity Capture-MS), VPS33A (Affinity Capture-Western), VPS18 (Affinity Capture-Western), VPS16 (Affinity Capture-Western), VPS16 (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), MTOR (Affinity Capture-MS), CFH (Affinity Capture-MS), PTK2 (Affinity Capture-MS)

ESM2 similar proteins: A0MT11, A1Z3X3, A2VD00, A4GWN3, A4II09, A4QNE0, A4VCH4, B5KFI0, O35841, P23116, P49754, Q09161, Q0P5I8, Q14152, Q15006, Q15386, Q1JU68, Q3B8M3, Q5E993, Q5E9L7, Q5KU39, Q5R4J9, Q5R644, Q5R882, Q5RE70, Q5XI83, Q5ZJZ6, Q5ZKG8, Q5ZMW3, Q68E01, Q6GLK9, Q6N069, Q6NRL4, Q6PCR7, Q6TGY8, Q6WKZ8, Q7L5D6, Q7TPD0, Q80UM3, Q8BHL5

Diamond homologs: Q55C58, Q5E9L7, Q920Q4, Q93VQ0, Q9H269, Q9UT38, Q9VHG1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
VPS16	“form complex”	“HOPS tethering complex”	binding
VPS16	“form complex”	“CORVET tethering complex”	binding
FUS	“down-regulates quantity by repression”	VPS16	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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
Transport of Mature mRNA derived from an Intron-Containing Transcript	6	9.9×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
endosomal vesicle fusion	7	57.8×	5e-09
endosome to lysosome transport	7	17.4×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	6
Uncertain significance	135
Likely benign	11
Benign	8

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
1065414	NM_022575.4(VPS16):c.1094_1095dup (p.Tyr366fs)	Pathogenic
1065416	NM_022575.4(VPS16):c.1367+2T>C	Pathogenic
1065417	NM_022575.4(VPS16):c.244_259delinsGAGAGC (p.Lys82fs)	Pathogenic
1065418	NM_022575.4(VPS16):c.156C>A (p.Asn52Lys)	Pathogenic
3342195	NM_022575.4(VPS16):c.1326T>A (p.Tyr442Ter)	Pathogenic
3905371	NM_022575.4(VPS16):c.436del (p.Ile146fs)	Pathogenic
4681731	NM_022575.4(VPS16):c.694C>T (p.Arg232Ter)	Pathogenic
4813602	NM_022575.4(VPS16):c.539G>A (p.Trp180Ter)	Pathogenic
976681	NM_022575.4(VPS16):c.1335T>G (p.Tyr445Ter)	Pathogenic
987017	NM_022575.4(VPS16):c.721_727del (p.Gly241fs)	Pathogenic
1347858	NM_022575.4(VPS16):c.1331+2T>C	Likely pathogenic
1695013	NM_022575.4(VPS16):c.1389C>G (p.Tyr463Ter)	Likely pathogenic
2663845	NM_022575.4(VPS16):c.143-2A>T	Likely pathogenic
4072035	NM_022575.4(VPS16):c.1818+2T>G	Likely pathogenic
4291133	NM_022575.4(VPS16):c.1513C>T (p.Arg505Ter)	Likely pathogenic
4531289	NM_022575.4(VPS16):c.1035dup (p.Gly346fs)	Likely pathogenic

SpliceAI

3733 predictions. Top by Δscore:

Variant	Effect	Δscore
20:2860444:CTCAG:C	acceptor_loss	1.0000
20:2860445:TCA:T	acceptor_loss	1.0000
20:2860446:CA:C	acceptor_loss	1.0000
20:2860447:A:AG	acceptor_gain	1.0000
20:2860447:A:C	acceptor_loss	1.0000
20:2860447:AG:A	acceptor_gain	1.0000
20:2860448:G:GG	acceptor_gain	1.0000
20:2860448:GG:G	acceptor_gain	1.0000
20:2860448:GGA:G	acceptor_gain	1.0000
20:2860448:GGAA:G	acceptor_gain	1.0000
20:2860588:TGCC:T	donor_gain	1.0000
20:2860589:GCCA:G	donor_gain	1.0000
20:2860590:CCAG:C	donor_gain	1.0000
20:2860591:CAGGT:C	donor_loss	1.0000
20:2860594:G:C	donor_loss	1.0000
20:2860594:G:GG	donor_gain	1.0000
20:2860595:T:A	donor_loss	1.0000
20:2860739:T:TA	acceptor_gain	1.0000
20:2860744:ATAG:A	acceptor_gain	1.0000
20:2860745:TA:T	acceptor_loss	1.0000
20:2860746:A:AG	acceptor_gain	1.0000
20:2860746:AG:A	acceptor_gain	1.0000
20:2860747:G:GT	acceptor_gain	1.0000
20:2860747:GG:G	acceptor_gain	1.0000
20:2860747:GGT:G	acceptor_gain	1.0000
20:2860747:GGTCT:G	acceptor_gain	1.0000
20:2860860:AGTGG:A	donor_loss	1.0000
20:2860861:GTG:G	donor_gain	1.0000
20:2860861:GTGGT:G	donor_loss	1.0000
20:2860864:G:A	donor_loss	1.0000

AlphaMissense

5478 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:2860269:T:A	W91R	1.000
20:2860269:T:C	W91R	1.000
20:2862105:T:C	L349P	1.000
20:2862113:G:C	A352P	1.000
20:2863384:T:A	W488R	1.000
20:2863384:T:C	W488R	1.000
20:2863386:G:C	W488C	1.000
20:2863386:G:T	W488C	1.000
20:2864040:C:A	A523D	1.000
20:2864180:T:C	L538P	1.000
20:2864260:G:C	A565P	1.000
20:2840796:T:A	W8R	0.999
20:2840796:T:C	W8R	0.999
20:2861279:T:A	W270R	0.999
20:2861279:T:C	W270R	0.999
20:2862105:T:A	L349H	0.999
20:2862114:C:A	A352D	0.999
20:2862607:T:C	L367P	0.999
20:2862656:C:G	C383W	0.999
20:2862811:C:A	A403D	0.999
20:2862820:G:A	G406E	0.999
20:2862828:T:C	F409L	0.999
20:2862830:C:A	F409L	0.999
20:2862830:C:G	F409L	0.999
20:2862877:T:C	L425P	0.999
20:2863385:G:C	W488S	0.999
20:2863388:C:A	A489D	0.999
20:2863398:G:C	K492N	0.999
20:2863398:G:T	K492N	0.999
20:2863992:T:A	I507N	0.999

dbSNP variants (sampled 300 via entrez): RS1000067326 (20:2841068 C>T), RS1000133986 (20:2840141 G>A), RS1000206164 (20:2846150 T>C), RS1000390265 (20:2840592 G>A), RS1000403838 (20:2862357 A>G), RS1000523206 (20:2840764 C>T), RS1000677106 (20:2840464 A>C,G,T), RS1000828801 (20:2858839 C>G), RS1000918801 (20:2856231 G>A), RS1001035278 (20:2850408 C>A), RS1001087567 (20:2844245 A>G), RS1001117525 (20:2839977 G>A), RS1001207020 (20:2847653 A>G), RS1001280369 (20:2841583 C>T), RS1001320329 (20:2850191 C>T)

Disease associations

OMIM: gene MIM:608550 | disease phenotypes: MIM:619291

GenCC curated gene-disease

Disease	Classification	Inheritance
dystonia 30	Strong	Autosomal dominant
mucopolysaccharidosis or mucopolysaccharidosis-like disorder	Strong	Autosomal recessive
isolated dystonia	Limited	Autosomal recessive

Mondo (5): dystonia 30 (MONDO:0025691), neutropenia (MONDO:0001475), peripheral neuropathy (MONDO:0005244), isolated dystonia (MONDO:0015494), mucopolysaccharidosis or mucopolysaccharidosis-like disorder (MONDO:0100365)

Orphanet (0):

HPO phenotypes

22 total (23 of 22 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000473	Torticollis
HP:0000718	Aggressive behavior
HP:0000722	Compulsive behaviors
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001332	Dystonia
HP:0002342	Moderate intellectual disability
HP:0002356	Writer’s cramp
HP:0002444	Hypothalamic hamartoma
HP:0002505	Loss of ambulation
HP:0002506	Diffuse cerebral atrophy
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0007302	Bipolar affective disorder
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0012048	Oromandibular dystonia
HP:0031959	Leg dystonia
HP:0031960	Arm dystonia
HP:0033049	Globus pallidus hypointensity on susceptibility-weighted imaging
HP:0100710	Impulsivity
HP:0001875	Decreased total neutrophil count

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009391_423	Metabolite levels	5.000000e-06
GCST009391_478	Metabolite levels	4.000000e-06
GCST90002389_414	Lymphocyte percentage of white cells	4.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010388	phosphatidylcholine 38:6 measurement
EFO:0010389	phosphatidylcholine 40:6 measurement
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
tetrabromobisphenol A	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Phthalic Acids	increases methylation	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Aflatoxin B1	increases methylation	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00125723	PHASE4	COMPLETED	FIRST - Study of Pegfilgrastim Administered in the First and Subsequent Cycles of Myelosuppressive Chemotherapy
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00257790	PHASE4	COMPLETED	The Tobramycin Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01114165	PHASE4	COMPLETED	Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
NCT01135589	PHASE4	UNKNOWN	Micafungin Prevention Study for Fungal Disease in Child Receiving Allogenic Hematopoietic Stem Cell Transplantation
NCT01571518	PHASE4	UNKNOWN	Prevention of Neutropenia After Using G-CSF With TAC Chemotherapy
NCT02621905	PHASE4	COMPLETED	Steady-State Comparative Bioavailability Study in Prophylaxis Patients of Lozanoc® 50 mg With Sporanox® 100 mg
NCT02967341	PHASE4	UNKNOWN	Blood Draw Validation for Ciprofloxacin Pharmacokinetic Research in Pediatric Cancer Patients
NCT04009941	PHASE4	COMPLETED	Efficacy and Safety of 4.5mg PEG-rhG-CSF Per Cycle in Preventing Neutropenia After Intensive Chemotherapy for Breast Cancer
NCT04904614	PHASE4	COMPLETED	Letermovir Use in Heart Transplant Recipients
NCT05626530	PHASE4	RECRUITING	Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients
NCT06145321	PHASE4	ACTIVE_NOT_RECRUITING	Continuous Versus Bolus Administration of G-CSF in Children With Cancer
NCT00380965	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	PHASE4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	PHASE4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	PHASE4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	PHASE4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	PHASE4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	PHASE4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	PHASE4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	PHASE4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT00001338	PHASE3	COMPLETED	A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00002658	PHASE3	UNKNOWN	Combination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia
NCT00002719	PHASE3	COMPLETED	Combination Chemotherapy With or Without G-CSF in Treating Older Patients With Acute Myeloid Leukemia
NCT00003739	PHASE3	COMPLETED	Antibiotic Therapy With or Without G-CSF in Treating Children With Neutropenia and Fever Caused by Chemotherapy
NCT00020865	PHASE3	UNKNOWN	Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia
NCT00035594	PHASE3	COMPLETED	Pegfilgrastim as Support to Advanced Breast Cancer Patients Receiving Chemotherapy
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00107081	PHASE3	TERMINATED	Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
NCT00445497	PHASE3	UNKNOWN	Early Hospital Discharge or Standard Inpatient Care in Cancer Patients Receiving Antibiotics for Febrile Neutropenia
NCT00529282	PHASE3	TERMINATED	A Study of Ceftobiprole in Patients With Fever and Neutropenia.
NCT00627393	PHASE3	COMPLETED	Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)
NCT00770172	PHASE3	COMPLETED	G-CSF in Preventing Neutropenia in Patients With Solid Tumors Who Are Receiving Chemotherapy