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.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	30	1	33
missense			76	3	1	80
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)			3			3
splice region			4	3	2	9
non coding				40	22	62
Total	0	0	82	73	24

Variants in VPS37A

This is a list of pathogenic ClinVar variants found in the VPS37A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-17247214-C-T			Likely benign (Mar 15, 2018)
8-17247226-G-A		not specified	Benign/Likely benign (Jul 06, 2017)
8-17247232-G-A			Likely benign (May 14, 2018)
8-17247266-A-C		not specified	Uncertain significance (Aug 25, 2024)
8-17247268-C-T		Hereditary spastic paraplegia 53 • Hereditary spastic paraplegia	Benign/Likely benign (Dec 06, 2023)
8-17247275-G-T		Hereditary spastic paraplegia 53	Uncertain significance (Jul 17, 2022)
8-17247276-C-G		Hereditary spastic paraplegia 53	Uncertain significance (Feb 25, 2022)
8-17247305-G-A			Uncertain significance (May 30, 2017)
8-17247316-C-T		Hereditary spastic paraplegia 53	Likely benign (Dec 31, 2019)
8-17247319-C-G		Hereditary spastic paraplegia 53	Likely benign (Mar 09, 2023)
8-17247321-A-C		not specified	Uncertain significance (Mar 21, 2023)
8-17247340-G-C		Hereditary spastic paraplegia 53 • VPS37A-related disorder	Likely benign (Sep 03, 2023)
8-17247340-G-T		Hereditary spastic paraplegia	Uncertain significance (Aug 01, 2018)
8-17247343-C-A		Hereditary spastic paraplegia 53	Conflicting classifications of pathogenicity (Jul 30, 2020)
8-17247377-G-A		Hereditary spastic paraplegia 53 • not specified • Hereditary spastic paraplegia	Benign (Jan 29, 2024)
8-17247378-TCGCTG-T		Hereditary spastic paraplegia 53	Likely benign (Aug 01, 2023)
8-17247384-C-T		Hereditary spastic paraplegia 53	Likely benign (Sep 01, 2022)
8-17247410-T-G			Likely benign (Sep 09, 2019)
8-17247414-A-G			Likely benign (Jun 28, 2018)
8-17247418-C-G			Likely benign (Sep 02, 2019)
8-17265891-A-C		Hereditary spastic paraplegia 53	Likely benign (Oct 20, 2022)
8-17265893-A-C		Hereditary spastic paraplegia 53	Likely benign (Aug 01, 2022)
8-17265906-G-C		Hereditary spastic paraplegia 53	Uncertain significance (May 04, 2022)
8-17265938-A-C		Hereditary spastic paraplegia 53	Likely benign (Sep 27, 2022)
8-17265940-A-G		Hereditary spastic paraplegia 53	Likely benign (Sep 01, 2024)

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

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