VPS33A

VPS33A core subunit of CORVET and HOPS complexes, the group of CORVET complex|HOPS complex

Basic information

Region (hg38): 12:122229564-122266502

Links

ENSG00000139719

∙ NCBI:65082 ∙ OMIM:610034 ∙ HGNC:18179 ∙ Uniprot:Q96AX1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

mucopolysaccharidosis-plus syndrome (Moderate), mode of inheritance: AR
mucopolysaccharidosis-plus syndrome (Strong), mode of inheritance: AR
mucopolysaccharidosis-plus syndrome (Limited), mode of inheritance: AR
mucopolysaccharidosis-plus syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucopolysaccharidosis-plus syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	27547915; 28013294

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS33A gene.

not_provided (238 variants)
not_specified (62 variants)
VPS33A-related_disorder (9 variants)
Mucopolysaccharidosis-plus_syndrome (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS33A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022916.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				84 clinvar	3 clinvar	87
missense		1 clinvar	122 clinvar	5 clinvar	3 clinvar	131
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	126	89	6

Highest pathogenic variant AF is 0.00000681537

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS33A	protein_coding	protein_coding	ENST00000267199	13	36958

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.182	0.818	125728	0	19	125747	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.64	263	349	0.754	0.0000201	3886
Missense in Polyphen		72	111	0.64865		1234
Synonymous	-0.626	153	143	1.07	0.00000868	1166
Loss of Function	4.01	8	32.8	0.244	0.00000185	375

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000279	0.000275
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000969	0.0000967
Middle Eastern	0.000110	0.000109
South Asian	0.0000330	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: 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 (PubMed:23351085, PubMed:24554770, PubMed:25266290, PubMed:25783203). Required for fusion of endosomes and autophagosomes with lysosomes; the function is dependent on its association with VPS16 but not VIPAS39 (PubMed:25783203). The function in autophagosome-lysosome fusion implicates STX17 but not UVRAG (PubMed:24554770). {ECO:0000269|PubMed:24554770, ECO:0000269|PubMed:25783203, ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:25266290, ECO:0000305|PubMed:25783203}.;
Disease: DISEASE: Mucopolysaccharidosis-plus syndrome (MPSPS) [MIM:617303]: A form of mucopolysaccharidosis, a group of diseases characterized by excessive accumulation and secretion of oligomucopoloysaccharides. MPSPS is a multisystemic disorder characterized by coarse facial features, dysostosis multiplex, hepatosplenomegaly, respiratory difficulties, mental retardation, 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. MPSPS inheritance is autosomal recessive. {ECO:0000269|PubMed:27547915, ECO:0000269|PubMed:28013294}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Ebola Virus Pathway on Host;Ebola Virus Pathway on Host (Consensus)

Recessive Scores

pRec: 0.163

Intolerance Scores

loftool: 0.565
rvis_EVS: 0.04
rvis_percentile_EVS: 57.31

Haploinsufficiency Scores

pHI: 0.306
hipred: N
hipred_score: 0.332
ghis: 0.537

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.987

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Vps33a
Phenotype: hematopoietic system phenotype; pigmentation phenotype; renal/urinary system phenotype; vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Gene ontology

Biological process: vesicle docking involved in exocytosis;endosome to lysosome transport;protein transport;vesicle-mediated transport;platelet formation;melanosome localization;lysosome localization;regulation of lysosomal lumen pH;regulation of developmental pigmentation;autophagosome maturation
Cellular component: lysosomal membrane;early endosome;late endosome;autophagosome;AP-3 adaptor complex;clathrin-coated vesicle;HOPS complex;late endosome membrane;perinuclear region of cytoplasm;clathrin complex
Molecular function: protein binding