VPS11

Summary

VPS11 (VPS11 core subunit of CORVET and HOPS complexes, HGNC:14583) is a protein-coding gene on chromosome 11q23.3, encoding Vacuolar protein sorting-associated protein 11 homolog (Q9H270). 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: 25.7% 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 Vps11 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. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55823 — RefSeq curated summary.

At a glance

• Gene–disease (curated): VPS11-related neurological disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 564 total — 1 pathogenic
• Phenotypes (HPO): 47
• Cancer dependency (DepMap): dependent in 25.7% of screened cell lines
• MANE Select transcript: NM_021729

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14583
Approved symbol	VPS11
Name	VPS11 core subunit of CORVET and HOPS complexes
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	RNF108, PEP5
Ensembl gene	ENSG00000160695
Ensembl biotype	protein_coding
OMIM	608549
Entrez	55823

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000524454, ENST00000526829, ENST00000529545, ENST00000530809, ENST00000534551, ENST00000614944, ENST00000621676, ENST00000622309, ENST00000863302, ENST00000863303, ENST00000952525, ENST00000952526

RefSeq mRNA: 6 — MANE Select: NM_021729 NM_001290185, NM_001378218, NM_001378219, NM_001378220, NM_001378221, NM_021729

CCDS: CCDS73404, CCDS76485

Canonical transcript exons

ENST00000621676 — 16 exons

Exon	Start	End
ENSE00003711926	119079129	119079300
ENSE00003718603	119069442	119069577
ENSE00003725920	119070234	119070397
ENSE00003726970	119078173	119078334
ENSE00003728360	119073198	119073399
ENSE00003729806	119077878	119078066
ENSE00003738459	119081092	119081314
ENSE00003738550	119076897	119077083
ENSE00003739383	119081459	119081972
ENSE00003741840	119067818	119068010
ENSE00003742485	119073800	119073951
ENSE00003744599	119071596	119071843
ENSE00003744907	119078565	119078704
ENSE00003747491	119069196	119069344
ENSE00003754319	119078795	119078997
ENSE00003791347	119077501	119077647

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.8290 / max 191.1711, expressed in 1814 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117084	17.7251	1814
117085	0.1038	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	94.01	gold quality
pituitary gland	UBERON:0000007	93.94	gold quality
apex of heart	UBERON:0002098	93.85	gold quality
frontal cortex	UBERON:0001870	93.80	gold quality
right frontal lobe	UBERON:0002810	93.74	gold quality
adenohypophysis	UBERON:0002196	93.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.40	gold quality
right adrenal gland	UBERON:0001233	93.39	gold quality
primary visual cortex	UBERON:0002436	93.37	gold quality
putamen	UBERON:0001874	93.33	gold quality
right adrenal gland cortex	UBERON:0035827	93.24	gold quality
cerebellum	UBERON:0002037	93.23	gold quality
cerebellar hemisphere	UBERON:0002245	93.21	gold quality
cerebellar cortex	UBERON:0002129	93.19	gold quality
granulocyte	CL:0000094	93.06	gold quality
cerebral cortex	UBERON:0000956	93.03	gold quality
caudate nucleus	UBERON:0001873	92.90	gold quality
brain	UBERON:0000955	92.88	gold quality
hypothalamus	UBERON:0001898	92.87	gold quality
left adrenal gland	UBERON:0001234	92.79	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.78	gold quality
spleen	UBERON:0002106	92.62	gold quality
Ammon’s horn	UBERON:0001954	92.49	gold quality
left adrenal gland cortex	UBERON:0035825	92.49	gold quality
anterior cingulate cortex	UBERON:0009835	92.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.45	gold quality
nucleus accumbens	UBERON:0001882	92.35	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.33	gold quality
substantia nigra	UBERON:0002038	92.22	gold quality
adrenal gland	UBERON:0002369	92.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting VPS11, 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-12119	99.87	68.35	1653
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-3907	96.76	65.04	662
HSA-MIR-711	96.60	65.75	528
HSA-MIR-4522	95.76	66.23	742
HSA-MIR-4693-3P	95.23	65.92	735

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• In Ashkenazi-Jewish patients, syndrome with hypomyelination, developmental delay, increasing appendicular spasticity, truncal hypotonia and acquired microcephaly is associated with VPS11 missense mutation, p.Cys846Gly. (PMID:26307567)
• our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway (PMID:27120463)
• Underlining the presumed pathogenic potential of VPS11 defects. (PMID:27473128)
• Study characterized the ubiquitinomes of Vps11/18 and demonstrated that these two factors are involved in the regulation of signal transduction by protein ubiquitination. VPS11/18 regulate several signaling factors and pathways, including Wnt, estrogen receptor alpha (ERalpha), and NFkappaB. (PMID:31015428)
• A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia. (PMID:33452836)
• Overexpression of VPS11 antagonizes the promoting effect of miR-542-3p on Mycobacterium tuberculosis survival in macrophages by regulating autophagy. (PMID:35662671)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vps11	ENSDARG00000036338
mus_musculus	Vps11	ENSMUSG00000032127
rattus_norvegicus	Vps11	ENSRNOG00000010733
drosophila_melanogaster	Vps11	FBGN0052350
caenorhabditis_elegans		WBGENE00011067

Paralogs (1): VPS18 (ENSG00000104142)

Protein

Protein identifiers

Vacuolar protein sorting-associated protein 11 homolog — Q9H270 (reviewed: Q9H270)

Alternative names: RING finger protein 108

All UniProt accessions (3): A0A087WXL6, A0A087X2J4, B7Z879

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 fusion of endosomes and autophagosomes with lysosomes. Involved in cargo transport from early to late endosomes and required for the transition from early to late endosomes. Involved in the retrograde Shiga toxin transport.

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 TGFBRAP1, MON1B, STX7, STX17, EZR, RDX, MSN, ECPAS. Interacts with RAB5C. Associates with adaptor protein complex 3 (AP-3) and clathrin:AP-3 complexes. Interacts with PLEKHM1.

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

Tissue specificity. Ubiquitous. Expression was highest in heart and low in lung.

Disease relevance. Leukodystrophy, hypomyelinating, 12 (HLD12) [MIM:616683] An autosomal recessive neurologic disorder characterized by developmental delay, spasticity, truncal hypotonia, acquired microcephaly, intellectual disability with variable seizure disorder, accompanied by thin corpus callosum, paucity of white matter and delayed myelination. The disease is caused by variants affecting the gene represented in this entry. Dystonia 32 (DYT32) [MIM:619637] A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT32 is an autosomal recessive, slowly progressive form with onset in adulthood and generalized involvement of the limbs, trunk, neck, and larynx, resulting in dysarthria and dysphagia. Brain imaging may show abnormalities in the basal ganglia. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the VPS11 family.

RefSeq proteins (6): NP_001277114, NP_001365147, NP_001365148, NP_001365149, NP_001365150, NP_068375* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000547	Clathrin_H-chain/VPS_repeat	Repeat
IPR001841	Znf_RING	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR016528	VPS11	Family
IPR024763	VPS11_C	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR057307	PEP5_VPS11_N	Domain
IPR057308	CHCR_PEP5_VPS11	Repeat

Pfam: PF12451, PF13923, PF23341, PF23356

UniProt features (16 total): modified residue 4, sequence variant 3, sequence conflict 3, repeat 2, initiator methionine 1, chain 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H270-F1	79.01	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 (4): 2, 813, 904, 924

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 334 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_LYSOSOMAL_TRANSPORT, GOBP_ENDOSOME_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, MODULE_45, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_MEMBRANE_FUSION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_ESTROGEN_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (18): intracellular protein transport (GO:0006886), obsolete vesicle docking involved in exocytosis (GO:0006904), autophagy (GO:0006914), endosome organization (GO:0007032), vacuole organization (GO:0007033), endosome to lysosome transport (GO:0008333), protein ubiquitination (GO:0016567), regulation of protein stability (GO:0031647), negative regulation of intracellular estrogen receptor signaling pathway (GO:0033147), endosomal vesicle fusion (GO:0034058), regulation of SNARE complex assembly (GO:0035542), positive regulation of protein catabolic process (GO:0045732), organelle fusion (GO:0048284), regulation of organelle assembly (GO:1902115), obsolete positive regulation of protein targeting to mitochondrion (GO:1903955), positive regulation of early endosome to late endosome transport (GO:2000643), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (8): nucleotide binding (GO:0000166), zinc ion binding (GO:0008270), protein domain specific binding (GO:0019904), syntaxin binding (GO:0019905), protein-macromolecule adaptor activity (GO:0030674), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

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), endocytic vesicle (GO:0030139), HOPS complex (GO:0030897), late endosome membrane (GO:0031902), CORVET complex (GO:0033263), actin filament (GO:0005884), endomembrane system (GO:0012505), membrane (GO:0016020), AP-3 adaptor complex (GO:0030123), cytoplasmic vesicle (GO:0031410), presynaptic active zone (GO:0048786), 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	4
cellular anatomical structure	3
intracellular protein localization	2
organelle organization	2
transport	2
protein binding	2
cytoplasmic vesicle	2
vacuole	2
vesicle tethering complex	2
protein transport	1
intracellular transport	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
endomembrane system organization	1
vesicle organization	1
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
protein modification by small protein conjugation	1
regulation of biological quality	1
estrogen receptor signaling pathway	1
negative regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of intracellular estrogen receptor signaling pathway	1
vesicle fusion	1
SNARE complex assembly	1
regulation of protein-containing complex assembly	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
regulation of organelle organization	1
regulation of cellular component biogenesis	1
organelle assembly	1
positive regulation of intracellular transport	1
early endosome to late endosome transport	1
regulation of early endosome to late endosome transport	1
establishment of protein localization	1
cellular process	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

1432 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS11	VPS39	Q96JC1	998
VPS11	VPS16	Q9H269	998
VPS11	VPS33A	Q96AX1	995
VPS11	VPS18	Q9P253	993
VPS11	VPS41	P49754	972
VPS11	VPS8	Q8N3P4	963
VPS11	TGFBRAP1	Q8WUH2	937
VPS11	VPS33B	Q9H267	759
VPS11	STX17	P56962	702
VPS11	CCZ1B	P86790	665
VPS11	MON1B	Q7L1V2	661
VPS11	VPS45	Q9NRW7	627
VPS11	VIPAS39	Q9H9C1	620
VPS11	VTI1B	Q9UEU0	617
VPS11	SQSTM1	Q13501	614

IntAct

166 interactions, top by confidence:

A	B	Type	Score
	VPS39	psi-mi:“MI:0914”(association)	0.960
	CLCC1	psi-mi:“MI:0914”(association)	0.870
TGFBRAP1	VPS11	psi-mi:“MI:0915”(physical association)	0.850
VPS11	TGFBRAP1	psi-mi:“MI:0914”(association)	0.850
VPS18	VPS16	psi-mi:“MI:0914”(association)	0.840
VPS11	VPS18	psi-mi:“MI:0915”(physical association)	0.830
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
VPS11	VPS39	psi-mi:“MI:0915”(physical association)	0.740
	HMOX1	psi-mi:“MI:0914”(association)	0.740
VPS33A	VPS11	psi-mi:“MI:0915”(physical association)	0.740
PLEKHM1	VPS41	psi-mi:“MI:0914”(association)	0.740
KRTAP10-8	VPS11	psi-mi:“MI:0915”(physical association)	0.720
VPS11	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
VPS11	VPS41	psi-mi:“MI:0914”(association)	0.710
VPS41	VPS11	psi-mi:“MI:0914”(association)	0.710
VPS41	VPS11	psi-mi:“MI:0915”(physical association)	0.710
VPS39	VPS11	psi-mi:“MI:0915”(physical association)	0.670
TMEM266	KDM1A	psi-mi:“MI:0914”(association)	0.670
VPS16	VPS41	psi-mi:“MI:0914”(association)	0.640
VPS11	Vps33a	psi-mi:“MI:0914”(association)	0.620
VPS11	Vps33a	psi-mi:“MI:0915”(physical association)	0.620

BioGRID (175): KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), VPS11 (Affinity Capture-RNA), VPS11 (Affinity Capture-RNA), VPS11 (Affinity Capture-RNA), VPS11 (Affinity Capture-MS), VPS39 (Affinity Capture-MS), TGFBRAP1 (Affinity Capture-MS), VPS18 (Affinity Capture-MS), VPS11 (Affinity Capture-MS), VPS11 (Affinity Capture-MS), VPS11 (Two-hybrid), VPS11 (Affinity Capture-Western), VPS11 (Reconstituted Complex), VPS11 (Reconstituted Complex)

ESM2 similar proteins: A0A3L7I2I8, A0FKG7, A2AGL3, A7MB89, B0LPN4, E9Q401, O60733, P30957, P42694, P49754, P97570, P97819, Q15413, Q29RM5, Q2KIX2, Q2T9K6, Q32PW3, Q3SX45, Q4V890, Q59H18, Q5F361, Q5GIG6, Q5KU39, Q5RF15, Q5U2S6, Q5ZKK2, Q66H07, Q66H63, Q6B858, Q6DFV5, Q6NYU2, Q7T3P8, Q7TQP6, Q8C0T1, Q8CEF1, Q8K0L0, Q8K114, Q8TC84, Q91W86, Q92736

Diamond homologs: Q54YP4, Q91W86, Q9H270, Q9SJ40, A5WW08, A8WWR3, A8Y4B2, D3ZSP7, F1QB30, O22255, O74757, O88196, O94400, P0CH30, P29128, P29836, P30631, P90990, Q07G42, Q08109, Q0IJ20, Q20798, Q3UF64, Q5BIY5, Q5FWP4, Q5SWK7, Q5XHH7, Q5Z880, Q641J8, Q6NPT7, Q6NRL6, Q6NTV1, Q75CC8, Q7KRW1, Q7T037, Q7TPV2, Q7X843, Q7XTV7, Q7ZWF4, Q803I8

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
VPS11	“up-regulates activity”	EZR	binding
VPS11	“up-regulates activity”	RDX	binding
Ub:E2	“up-regulates activity”	VPS11	ubiquitination
VPS11	“form complex”	“HOPS tethering complex”	binding
VPS11	“form complex”	“CORVET tethering complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 122 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
endosomal vesicle fusion	7	73.5×	1e-09
endosome to lysosome transport	9	28.4×	8e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	122
Likely benign	382
Benign	34

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1326861	NM_021729.6(VPS11):c.1158_1184del (p.Leu387_Gly395del)	Pathogenic

SpliceAI

2568 predictions. Top by Δscore:

Variant	Effect	Δscore
11:119068064:T:G	donor_gain	1.0000
11:119068162:G:GT	donor_gain	1.0000
11:119068162:G:T	donor_gain	1.0000
11:119069343:TGG:T	donor_loss	1.0000
11:119069345:GT:G	donor_loss	1.0000
11:119069346:TGAGT:T	donor_loss	1.0000
11:119069347:GA:G	donor_loss	1.0000
11:119069515:G:GT	donor_gain	1.0000
11:119069516:A:T	donor_gain	1.0000
11:119070230:ACAG:A	acceptor_gain	1.0000
11:119070231:C:G	acceptor_gain	1.0000
11:119070232:A:AG	acceptor_gain	1.0000
11:119070232:AG:A	acceptor_gain	1.0000
11:119070233:G:GC	acceptor_gain	1.0000
11:119070233:GG:G	acceptor_gain	1.0000
11:119070233:GGT:G	acceptor_gain	1.0000
11:119070233:GGTT:G	acceptor_gain	1.0000
11:119070233:GGTTT:G	acceptor_gain	1.0000
11:119070354:G:GT	donor_gain	1.0000
11:119070355:A:T	donor_gain	1.0000
11:119070394:CCAG:C	donor_loss	1.0000
11:119070398:G:GG	donor_gain	1.0000
11:119070398:GTATG:G	donor_loss	1.0000
11:119071770:GGCCA:G	donor_gain	1.0000
11:119071844:G:GG	donor_gain	1.0000
11:119073197:GGTCA:G	acceptor_gain	1.0000
11:119073298:G:GT	donor_gain	1.0000
11:119073317:C:G	donor_gain	1.0000
11:119073798:A:AG	acceptor_gain	1.0000
11:119073798:AGAT:A	acceptor_gain	1.0000

AlphaMissense

6231 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:119069451:T:A	W116R	1.000
11:119069451:T:C	W116R	1.000
11:119073897:G:A	G395E	1.000
11:119073933:C:A	A407D	1.000
11:119076965:T:C	L436P	1.000
11:119076977:T:C	L440P	1.000
11:119077025:T:C	L456P	1.000
11:119077028:T:C	L457P	1.000
11:119081117:T:A	C822S	1.000
11:119081117:T:C	C822R	1.000
11:119081118:G:C	C822S	1.000
11:119081119:C:G	C822W	1.000
11:119081126:T:C	C825R	1.000
11:119081127:G:A	C825Y	1.000
11:119081159:T:C	F836L	1.000
11:119081161:C:A	F836L	1.000
11:119081161:C:G	F836L	1.000
11:119081165:T:C	C838R	1.000
11:119081180:C:G	H843D	1.000
11:119081189:T:C	C846R	1.000
11:119081191:C:G	C846W	1.000
11:119081222:T:C	C857R	1.000
11:119067842:T:A	W7R	0.999
11:119067842:T:C	W7R	0.999
11:119068008:G:A	G62E	0.999
11:119069304:T:C	L99P	0.999
11:119069309:T:C	S101P	0.999
11:119069313:T:A	V102D	0.999
11:119069315:G:A	G103R	0.999
11:119069315:G:C	G103R	0.999

dbSNP variants (sampled 300 via entrez): RS1000064376 (11:119078513 A>G), RS1000491172 (11:119067515 C>G), RS1000737270 (11:119072686 G>A), RS1000836822 (11:119077718 T>G), RS1000947177 (11:119068343 T>G), RS1000981593 (11:119068168 C>G,T), RS1000991347 (11:119071709 C>A,G,T), RS1001124639 (11:119073356 G>A,C), RS1001175124 (11:119073648 G>T), RS1001277139 (11:119067562 T>C), RS1001730690 (11:119081564 T>A,C), RS1001834005 (11:119074988 C>T), RS1002098052 (11:119081882 A>G), RS1002177649 (11:119072307 A>C,T), RS1002334252 (11:119066393 C>T)

Disease associations

OMIM: gene MIM:608549 | disease phenotypes: MIM:616683, MIM:619637

GenCC curated gene-disease

Disease	Classification	Inheritance
hypomyelinating leukodystrophy 12	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
VPS11-related neurological disorder	Definitive	AR

Mondo (2): hypomyelinating leukodystrophy 12 (MONDO:0014732), dystonia 32 (MONDO:0030486)

Orphanet (1): VPS11-related autosomal recessive hypomyelinating leukodystrophy (Orphanet:466934)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000473	Torticollis
HP:0000648	Optic atrophy
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001344	Absent speech
HP:0001371	Flexion contracture
HP:0001433	Hepatosplenomegaly
HP:0001510	Growth delay
HP:0002015	Dysphagia
HP:0002019	Constipation
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002188	Delayed CNS myelination
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002384	Focal impaired awareness seizure
HP:0002395	Lower limb hyperreflexia
HP:0002451	Limb dystonia
HP:0002465	Poor speech
HP:0002518	Abnormal periventricular white matter morphology

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005194_208	Coronary artery disease	8.000000e-07
GCST008129_24	Body mass index	9.000000e-12
GCST010242_431	HDL cholesterol levels	2.000000e-21
GCST010866_88	Coronary artery disease	7.000000e-09
GCST010988_430	Adult body size	6.000000e-11
GCST90002400_477	Plateletcrit	4.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects expression	3
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tetrabromobisphenol A	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Amiodarone	increases expression	1
Arsenic	increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Gold Compounds	increases expression, decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2NQ	HAP1 VPS11 (-) 1	Cancer cell line	Male
CVCL_E2NR	HAP1 VPS11 (-) 2	Cancer cell line	Male
CVCL_E2NS	HAP1 VPS11 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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