VPS33A

Summary

VPS33A (VPS33A core subunit of CORVET and HOPS complexes, HGNC:18179) is a protein-coding gene on chromosome 12q24.31, encoding Vacuolar protein sorting-associated protein 33A (Q96AX1). 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: 69.3% of cell lines).

This gene encodes a tethering protein and a core subunit of the homotypic fusion and protein sorting (HOPS) complex. The HOPS complex and a second endosomal tethering complex called the class C core vacuole/endosome tethering (CORVET) complex, perform diverse functions in endocytosis including membrane tethering, RabGTPase interaction, activation and proofreading of synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) assembly to drive membrane fusion, and endosome-to-cytoskeleton attachment. The HOPS complex controls endosome maturation as well as endosome traffic to the lysosome. This complex is essential for vacuolar fusion and is required for adaptor protein complex 3-dependent transport from the golgi to the vacuole. The encoded protein belongs to the Sec1/Munc18 (SM) family of SNARE-mediated membrane fusion regulators. Naturally occurring mutations in this gene are associated with a novel mucopolysaccharidosis-like disease.

Source: NCBI Gene 65082 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mucopolysaccharidosis-plus syndrome (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 367 total — 1 likely-pathogenic
• Phenotypes (HPO): 101
• Cancer dependency (DepMap): dependent in 69.3% of screened cell lines
• MANE Select transcript: NM_022916

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18179
Approved symbol	VPS33A
Name	VPS33A core subunit of CORVET and HOPS complexes
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000139719
Ensembl biotype	protein_coding
OMIM	610034
Entrez	65082

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 22 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000267199, ENST00000451053, ENST00000536212, ENST00000540669, ENST00000541169, ENST00000542790, ENST00000543633, ENST00000544349, ENST00000643696, ENST00000714042, ENST00000714043, ENST00000714044, ENST00000714045, ENST00000714049, ENST00000714050, ENST00000714051, ENST00000883789, ENST00000883790, ENST00000883791, ENST00000932481, ENST00000932482, ENST00000932483, ENST00000932484, ENST00000932485, ENST00000932486, ENST00000932487, ENST00000932488, ENST00000932489

RefSeq mRNA: 5 — MANE Select: NM_022916 NM_001351018, NM_001351019, NM_001351020, NM_001351021, NM_022916

CCDS: CCDS86339, CCDS9231

Canonical transcript exons

ENST00000267199 — 13 exons

Exon	Start	End
ENSE00001122284	122229564	122232427
ENSE00001216759	122266307	122266494
ENSE00003472691	122242382	122242508
ENSE00003500995	122249871	122250045
ENSE00003509271	122244569	122244762
ENSE00003519665	122239878	122239945
ENSE00003542472	122235786	122235923
ENSE00003553526	122250983	122251099
ENSE00003557877	122232800	122232968
ENSE00003592714	122261261	122261447
ENSE00003620225	122263572	122263699
ENSE00003633533	122264134	122264199
ENSE00003661023	122238587	122238724

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 88.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1922 / max 172.2434, expressed in 1817 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133800	9.8923	1803
133799	4.2998	1645

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	88.42	silver quality
monocyte	CL:0000576	87.85	gold quality
endothelial cell	CL:0000115	87.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.08	gold quality
leukocyte	CL:0000738	87.06	gold quality
tendon of biceps brachii	UBERON:0008188	87.01	silver quality
mononuclear cell	CL:0000842	86.92	gold quality
adrenal tissue	UBERON:0018303	86.58	gold quality
right testis	UBERON:0004534	85.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.87	gold quality
granulocyte	CL:0000094	85.72	gold quality
cortical plate	UBERON:0005343	85.53	gold quality
left testis	UBERON:0004533	85.42	gold quality
gastrocnemius	UBERON:0001388	85.00	gold quality
testis	UBERON:0000473	84.89	gold quality
ventricular zone	UBERON:0003053	84.77	gold quality
islet of Langerhans	UBERON:0000006	84.63	gold quality
muscle of leg	UBERON:0001383	84.63	gold quality
tendon	UBERON:0000043	84.55	gold quality
calcaneal tendon	UBERON:0003701	84.45	gold quality
stromal cell of endometrium	CL:0002255	84.07	gold quality
prefrontal cortex	UBERON:0000451	84.03	gold quality
ganglionic eminence	UBERON:0004023	83.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.42	gold quality
blood	UBERON:0000178	83.39	gold quality
right adrenal gland	UBERON:0001233	83.34	gold quality
mucosa of transverse colon	UBERON:0004991	83.19	gold quality
right adrenal gland cortex	UBERON:0035827	83.11	gold quality
primary visual cortex	UBERON:0002436	82.86	gold quality
colonic epithelium	UBERON:0000397	82.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	386.08
E-ANND-3	no	4.30

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 69.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• VPS33A is mutated in Hermansky-Pudlak syndrome and may have a role in melanogenesis (PMID:12538872)
• A and B classes reflect the evolution of organelle/tissue-specific functions (PMID:15790593)
• Melanoma cells depleted of vacuolar protein sorting 33A protein have increased nuclear localization of cis-diaminedichloroplatinum II, increased nuclear DNA damage by platination, and increased apoptosis, resulting in increased treatment sensitivity. (PMID:22203954)
• association of VPS33A with HOPS via its interaction with VPS16 is required for both endosome- and autophagosome-lysosome fusion (PMID:25783203)
• The clinical phenotype and genetic studies support the suggestion that the siblings most probably have a novel disease very likely caused by a VPS33A gene defect. (PMID:27547915)
• Mutations in VPS33A is associated with mucopolysaccharidosis with severe systemic symptoms. (PMID:28013294)
• Data suggest that accumulation of autophagosomes confers cytotoxicity in a number of cell types including neurons mimicking neurodegeneration; RNA interference of combinations of MTOR, VPS33A, and STX17 lead to accumulation of autophagosomes and cytotoxicity. (MTOR = mechanistic target of rapamycin kinase; VPS33A = vacuolar protein sorting 33A; STX17 = syntaxin 17) (PMID:28673965)
• It identified multimodal regulation of SNARE assembly by the Sec1/Munc18 (SM) protein VPS33A, mirroring other syntaxin-SM interactions and therefore suggesting a unified model of SM regulation. (PMID:30655294)
• Since the inhibition of autolysosome formation plays a critical role in tuberculosis occurrence, these fi ndings suggests that miR-423-5p could suppress autophagosome-lysosome fusion by post-transcriptional regulation of VPS33A, which might be important for the occurrence of active tuberculosis. (PMID:30898038)
• The lysosomal disease caused by mutant VPS33A. (PMID:31070736)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vps33a	ENSDARG00000101116
mus_musculus	Vps33a	ENSMUSG00000029434
rattus_norvegicus	Vps33a	ENSRNOG00000056889
drosophila_melanogaster	car	FBGN0000257
caenorhabditis_elegans		WBGENE00015130

Paralogs (7): STXBP2 (ENSG00000076944), SCFD1 (ENSG00000092108), STXBP3 (ENSG00000116266), VPS45 (ENSG00000136631), STXBP1 (ENSG00000136854), VPS33B (ENSG00000184056), SCFD2 (ENSG00000184178)

Protein

Protein identifiers

Vacuolar protein sorting-associated protein 33A — Q96AX1 (reviewed: Q96AX1)

All UniProt accessions (13): Q96AX1, A0A2R8Y5F6, A0A2R8Y5U3, A0A2R8YF87, A0AAQ5BHA6, A0AAQ5BHB6, A0AAQ5BHD6, A0AAQ5BHD7, A0AAQ5BHD8, A0AAQ5BHF8, F5H2X5, F5H6Y0, F5H7N5

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; the function is dependent on its association with VPS16 but not VIPAS39. 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 UVRAG, STX17, MON1A and MON1B. Interacts with VIPAS39; however, this interaction is debated. Associates with adaptor protein complex 3 (AP-3) and clathrin. Interacts with PLEKHM1.

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

Disease relevance. Mucopolysaccharidosis-plus syndrome (MPSPS) [MIM:617303] A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPSPS is an autosomal recessive form characterized by coarse facial features, dysostosis multiplex, hepatosplenomegaly, respiratory difficulties, intellectual disability, developmental delay, pyramidal signs, severe chronic anemia, renal involvement and cardiac defects. Laboratory analyses show proteinuria with glomerular foamy cells, excess secretion of urinary glycosaminoglycans, and extremely high levels of plasma heparan sulphate. Disease onset is in infancy. Most patients die in the first years of life due to cardiorespiratory failure. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the STXBP/unc-18/SEC1 family.

RefSeq proteins (5): NP_001337947, NP_001337948, NP_001337949, NP_001337950, NP_075067* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001619	Sec1-like	Family
IPR027482	Sec1-like_dom2	Homologous_superfamily
IPR036045	Sec1-like_sf	Homologous_superfamily
IPR043127	Sec-1-like_dom3a	Homologous_superfamily
IPR043154	Sec-1-like_dom1	Homologous_superfamily
IPR043155	VPS33_dom3b	Homologous_superfamily

Pfam: PF00995

UniProt features (58 total): helix 30, strand 21, mutagenesis site 3, sequence variant 2, chain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4BX8	X-RAY DIFFRACTION	2.4
4BX9	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AX1-F1	94.05	0.87

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
429	disrupts interaction with vps16. disrupts interaction with vps18 and impairs endosome-lysosome fusion; when associated w
438	disrupts interaction with vps16. disrupts interaction with vps18 and impairs endosome-lysosome fusion; when associated w
441	disrupts interaction with vps16. disrupts interaction with vps18 and impairs endosome-lysosome fusion; when associated w

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 414 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_PIGMENT_GRANULE_LOCALIZATION, GOBP_LYSOSOMAL_TRANSPORT, GOBP_VACUOLE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_MEMBRANE_FUSION, GOBP_CELLULAR_PIGMENTATION, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MACROAUTOPHAGY

GO Biological Process (14): intracellular protein transport (GO:0006886), endosome to lysosome transport (GO:0008333), vesicle-mediated transport (GO:0016192), platelet formation (GO:0030220), melanosome localization (GO:0032400), lysosome localization (GO:0032418), endosomal vesicle fusion (GO:0034058), regulation of SNARE complex assembly (GO:0035542), obsolete regulation of lysosomal lumen pH (GO:0035751), regulation of developmental pigmentation (GO:0048070), autophagosome maturation (GO:0097352), autophagy (GO:0006914), protein transport (GO:0015031), pigmentation (GO:0043473)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (16): lysosome (GO:0005764), lysosomal membrane (GO:0005765), early endosome (GO:0005769), late endosome (GO:0005770), autophagosome (GO:0005776), endosome membrane (GO:0010008), clathrin-coated vesicle (GO:0030136), HOPS complex (GO:0030897), late endosome membrane (GO:0031902), CORVET complex (GO:0033263), perinuclear region of cytoplasm (GO:0048471), endosome (GO:0005768), membrane (GO:0016020), AP-3 adaptor complex (GO:0030123), cytoplasmic vesicle (GO:0031410), clathrin complex (GO:0071439)

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
intracellular protein localization	2
transport	2
membrane protein complex	2
vesicle tethering complex	2
cytoplasm	2
cellular anatomical structure	2
protein transport	1
intracellular transport	1
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
cellular process	1
myeloid cell differentiation	1
platelet morphogenesis	1
anatomical structure formation involved in morphogenesis	1
pigment granule localization	1
vacuolar localization	1
vesicle fusion	1
SNARE complex assembly	1
regulation of protein-containing complex assembly	1
developmental pigmentation	1
regulation of pigmentation	1
macroautophagy	1
protein-containing complex disassembly	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
establishment of protein localization	1
biological_process	1
binding	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
vacuole	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
coated vesicle	1
late endosome	1
endosome membrane	1

Protein interactions and networks

STRING

1640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS33A	VPS18	Q9P253	997
VPS33A	VPS16	Q9H269	997
VPS33A	VPS11	Q9H270	995
VPS33A	VPS39	Q96JC1	993
VPS33A	VIPAS39	Q9H9C1	963
VPS33A	STX7	O15400	836
VPS33A	STX17	P56962	831
VPS33A	STX8	Q9UNK0	830
VPS33A	STX12	Q86Y82	814
VPS33A	TGFBRAP1	Q8WUH2	796
VPS33A	VPS8	Q8N3P4	792
VPS33A	VPS41	P49754	758
VPS33A	SNAP29	O95721	698
VPS33A	VAMP8	Q9BV40	675
VPS33A	RAB11A	P24410	654

IntAct

135 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
VPS33A	VPS11	psi-mi:“MI:0915”(physical association)	0.740
PLEKHM1	VPS41	psi-mi:“MI:0914”(association)	0.740
VPS18	VPS33A	psi-mi:“MI:0915”(physical association)	0.720
VPS33A	VPS18	psi-mi:“MI:0915”(physical association)	0.720
VPS11	VPS41	psi-mi:“MI:0914”(association)	0.710
	VPS41	psi-mi:“MI:0914”(association)	0.690
VPS16	VPS41	psi-mi:“MI:0914”(association)	0.640
PLEKHM1	VPS33A	psi-mi:“MI:0914”(association)	0.600
VPS33A	UVRAG	psi-mi:“MI:0915”(physical association)	0.560
VPS33A	ROPN1	psi-mi:“MI:0915”(physical association)	0.560
A2M	VPS33A	psi-mi:“MI:0915”(physical association)	0.560
SERPINA3	VPS33A	psi-mi:“MI:0915”(physical association)	0.560
CASP8	VPS33A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (312): VPS33A (Affinity Capture-MS), VPS33A (Affinity Capture-MS), VPS33A (Affinity Capture-MS), VPS33A (Affinity Capture-MS), VPS33A (Affinity Capture-MS), VPS33A (Affinity Capture-MS), VPS18 (Co-fractionation), VPS33A (Co-fractionation), VPS33A (Affinity Capture-MS), VPS33A (Affinity Capture-Western), VPS33A (Affinity Capture-Western), VPS18 (Affinity Capture-Western), VPS33A (Affinity Capture-MS), VPS33A (Proximity Label-MS), VPS33A (Affinity Capture-MS)

ESM2 similar proteins: O00186, O01757, O08599, O08700, O18637, O74534, O94590, P22213, P34815, P38932, P61763, P61764, P61765, P97390, Q07327, Q09805, Q15833, Q18891, Q24087, Q24179, Q28288, Q54GE3, Q54IJ1, Q54QC8, Q5R6D2, Q5VNU3, Q60770, Q62753, Q62991, Q64324, Q6BZX4, Q6R748, Q7XWP3, Q851W1, Q8BRF7, Q8LPK4, Q8LPL6, Q8SS97, Q8WVM8, Q94KJ7

Diamond homologs: P59016, Q2HJ18, Q58EN8, Q63615, Q63616, Q94KJ7, Q96AX1, Q9D2N9, Q9H267, Q9P7V6, Q9Y1I2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
VPS33A	“form complex”	“HOPS tethering complex”	binding
VPS33A	“form complex”	“CORVET tethering complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 128 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
Membrane Trafficking	11	4.5×	7e-03
Vesicle-mediated transport	11	4.3×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
endosomal vesicle fusion	7	67.8×	1e-09
endosome to lysosome transport	8	23.2×	4e-07
autophagy	8	7.6×	1e-03
intracellular protein transport	11	6.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	144
Likely benign	155
Benign	46

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
374985	NM_022916.6(VPS33A):c.1492C>T (p.Arg498Trp)	Likely pathogenic

SpliceAI

1796 predictions. Top by Δscore:

Variant	Effect	Δscore
12:122232177:T:TA	donor_gain	1.0000
12:122232327:T:TA	donor_gain	1.0000
12:122232794:ACTT:A	donor_loss	1.0000
12:122232795:CTT:C	donor_loss	1.0000
12:122232796:TTACG:T	donor_loss	1.0000
12:122232797:TAC:T	donor_loss	1.0000
12:122232797:TACGT:T	donor_loss	1.0000
12:122232798:A:AC	donor_gain	1.0000
12:122232798:AC:A	donor_loss	1.0000
12:122232799:C:A	donor_loss	1.0000
12:122232799:C:CA	donor_gain	1.0000
12:122232799:C:CC	donor_gain	1.0000
12:122232799:CG:C	donor_gain	1.0000
12:122232799:CGT:C	donor_gain	1.0000
12:122232799:CGTTT:C	donor_gain	1.0000
12:122232964:GGGTT:G	acceptor_gain	1.0000
12:122232965:GGTT:G	acceptor_gain	1.0000
12:122232966:GTT:G	acceptor_gain	1.0000
12:122232967:TT:T	acceptor_gain	1.0000
12:122232968:TC:T	acceptor_loss	1.0000
12:122232969:C:CC	acceptor_gain	1.0000
12:122232969:C:CG	acceptor_loss	1.0000
12:122232976:A:C	acceptor_gain	1.0000
12:122235784:A:AC	donor_gain	1.0000
12:122235785:C:CC	donor_gain	1.0000
12:122235785:CTTG:C	donor_gain	1.0000
12:122235921:TGT:T	acceptor_gain	1.0000
12:122238582:CTCA:C	donor_loss	1.0000
12:122238583:TCA:T	donor_loss	1.0000
12:122238584:CA:C	donor_loss	1.0000

AlphaMissense

3900 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:122232352:C:G	R562P	1.000
12:122232367:T:A	E557V	1.000
12:122232887:A:G	W508R	1.000
12:122232887:A:T	W508R	1.000
12:122232913:A:G	L499P	1.000
12:122232916:C:G	R498P	1.000
12:122232921:A:C	S496R	1.000
12:122232921:A:T	S496R	1.000
12:122232923:T:G	S496R	1.000
12:122232928:G:C	P494R	1.000
12:122232931:G:T	A493D	1.000
12:122242406:C:G	A358P	1.000
12:122242426:A:G	L351P	1.000
12:122242456:A:G	L341S	1.000
12:122242465:A:T	V338D	1.000
12:122242467:A:C	F337L	1.000
12:122242467:A:T	F337L	1.000
12:122242469:A:G	F337L	1.000
12:122244595:C:G	A315P	1.000
12:122244606:A:G	L311P	1.000
12:122244618:A:T	V307D	1.000
12:122244639:C:G	R300P	1.000
12:122249900:A:G	L249P	1.000
12:122249904:C:G	G248R	1.000
12:122249904:C:T	G248R	1.000
12:122250996:C:A	G196V	1.000
12:122250996:C:T	G196E	1.000
12:122250997:C:G	G196R	1.000
12:122250997:C:T	G196R	1.000
12:122251002:C:T	G194E	1.000

dbSNP variants (sampled 300 via entrez): RS1000059412 (12:122252862 T>C), RS1000193873 (12:122235594 C>T), RS1000288041 (12:122229176 C>T), RS1000385697 (12:122247732 G>C), RS1000424084 (12:122241095 T>C), RS1000453892 (12:122241484 T>C), RS1000558007 (12:122237304 G>A), RS1000585980 (12:122268173 G>A,C), RS1000629477 (12:122235994 C>G,T), RS1000754154 (12:122242639 G>A), RS1000763609 (12:122233596 A>G), RS1000785509 (12:122242846 G>A,T), RS1000828432 (12:122264625 C>A,T), RS1000931735 (12:122237052 A>G), RS1000998485 (12:122231453 G>A,T)

Disease associations

OMIM: gene MIM:610034 | disease phenotypes: MIM:617303

GenCC curated gene-disease

Disease	Classification	Inheritance
mucopolysaccharidosis-plus syndrome	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mucopolysaccharidosis-plus syndrome	Definitive	AR

Mondo (1): mucopolysaccharidosis-plus syndrome (MONDO:0015012)

Orphanet (1): Mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders (Orphanet:505248)

HPO phenotypes

101 total (30 of 101 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000092	Renal tubular atrophy
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000105	Enlarged kidney
HP:0000123	Nephritis
HP:0000158	Macroglossia
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000470	Short neck
HP:0000506	Telecanthus
HP:0000509	Conjunctivitis
HP:0000527	Long eyelashes
HP:0000629	Periorbital fullness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000664	Synophrys
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000943	Dysostosis multiplex
HP:0000998	Hypertrichosis
HP:0001007	Hirsutism
HP:0001072	Thickened skin

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90020028_964	Hip circumference adjusted for BMI	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	affects expression, affects cotreatment, increases oxidation, increases abundance	2
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
lead acetate	affects cotreatment, decreases expression	1
zinc protoporphyrin	affects cotreatment, decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Thiram	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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