VPS37A

VPS37A subunit of ESCRT-I, the group of ESCRT-I

Basic information

Region (hg38): 8:17246931-17302427

Previous symbols: [ "PQBP2" ]

Links

ENSG00000155975

∙ NCBI:137492 ∙ OMIM:609927 ∙ HGNC:24928 ∙ Uniprot:Q8NEZ2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hereditary spastic paraplegia 53 (Supportive), mode of inheritance: AR
hereditary spastic paraplegia 53 (Limited), mode of inheritance: AR
hereditary spastic paraplegia 53 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 53, autosomal recessive	AR	General	The use of botulinum has been described as beneficial for treating spasticity in some individuals, though the advantage of genetic diagnosis is unclear; 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	Neurologic	22717650

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS37A gene.

Hereditary_spastic_paraplegia_53 (136 variants)
not_specified (66 variants)
not_provided (34 variants)
Hereditary_spastic_paraplegia (16 variants)
VPS37A-related_disorder (6 variants)
Idiopathic_transverse_myelitis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS37A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000152415.3. 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			3 clinvar	33 clinvar		36
missense	1 clinvar	1 clinvar	107 clinvar	4 clinvar	1 clinvar	114
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	1	113	37	1

Highest pathogenic variant AF is 0.000262547

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS37A	protein_coding	protein_coding	ENST00000324849	11	55857

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000679	0.996	125721	0	16	125737	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.885	235	200	1.18	0.00000897	2603
Missense in Polyphen		37	48.493	0.76299		678
Synonymous	-1.82	92	72.3	1.27	0.00000352	731
Loss of Function	2.53	9	21.7	0.414	0.00000102	276

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000150	0.000150
Ashkenazi Jewish	0.000202	0.0000992
East Asian	0.000110	0.000109
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.0000355	0.0000352
Middle Eastern	0.000110	0.000109
South Asian	0.000102	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in cell growth and differentiation. {ECO:0000269|PubMed:15240819}.;
Pathway: Endocytosis - Homo sapiens (human);Disease;Vesicle-mediated transport;Membrane Trafficking;Assembly Of The HIV Virion;Budding and maturation of HIV virion;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;Endosomal Sorting Complex Required For Transport (ESCRT);Infectious disease;Membrane binding and targetting of GAG proteins;Synthesis And Processing Of GAG, GAGPOL Polyproteins (Consensus)

Intolerance Scores

loftool: 0.592
rvis_EVS: -0.54
rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

pHI: 0.130
hipred: Y
hipred_score: 0.825
ghis: 0.619

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.904

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Vps37a
Phenotype

Zebrafish Information Network

Gene name: vps37a
Affected structure: whole organism
Phenotype tag: abnormal
Phenotype quality: decreased mobility

Gene ontology

Biological process: protein targeting to membrane;protein targeting to vacuole;protein transport;endosomal transport;macroautophagy;viral life cycle;endosome transport via multivesicular body sorting pathway;multivesicular body assembly;viral budding via host ESCRT complex;ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
Cellular component: ESCRT I complex;nucleoplasm;centrosome;cytosol;endosome membrane;late endosome membrane;intracellular membrane-bounded organelle
Molecular function: protein binding