VAPA

VAMP associated protein A

Basic information

Region (hg38): 18:9914015-9960021

Links

ENSG00000101558 ∙ NCBI:9218 ∙ OMIM:605703 ∙ HGNC:12648 ∙ Uniprot:Q9P0L0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (14 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VAPA 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						0
missense			11			11
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			3	1		4
Total	0	0	14	1	0

Variants in VAPA

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

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

Position	Type	Phenotype	Significance	ClinVar
18-9914267-C-T		not specified	Uncertain significance (Feb 08, 2023)
18-9914328-A-C		not specified	Uncertain significance (May 18, 2023)
18-9931831-C-T		not specified	Uncertain significance (Apr 07, 2023)
18-9936190-A-G		not specified	Uncertain significance (May 18, 2023)
18-9944988-C-G		not specified	Uncertain significance (Dec 20, 2023)
18-9944991-C-T		not specified	Uncertain significance (May 18, 2022)
18-9945008-A-G		not specified	Uncertain significance (Apr 17, 2023)
18-9945019-C-T			Likely benign (Sep 01, 2022)
18-9945032-A-T		not specified	Uncertain significance (Dec 21, 2022)
18-9950423-C-G		not specified	Uncertain significance (Apr 18, 2023)
18-9950423-C-T		not specified	Uncertain significance (Nov 09, 2022)
18-9950439-G-C		not specified	Uncertain significance (Sep 25, 2023)
18-9950458-A-G		not specified	Uncertain significance (Sep 16, 2021)
18-9950476-C-T		not specified	Uncertain significance (Jul 08, 2022)
18-9950480-A-G		not specified	Uncertain significance (Dec 03, 2021)
18-9950558-G-A		not specified	Uncertain significance (Jun 09, 2022)
18-9954116-T-A		not specified	Uncertain significance (May 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VAPA	protein_coding	protein_coding	ENST00000340541	7	46020

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.353	0.644	124766	0	8	124774	0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.953	125	159	0.787	0.00000776	1929
Missense in Polyphen		8	25.502	0.31371		358
Synonymous	0.544	53	58.3	0.909	0.00000307	555
Loss of Function	2.60	3	13.2	0.228	6.37e-7	172

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000223	0.000223
Finnish	0.0000482	0.0000464
European (Non-Finnish)	0.0000322	0.0000265
Middle Eastern	0.000223	0.000223
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to OSBPL3, which mediates recruitment of VAPA to plasma membrane sites (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:25447204). With OSBPL3, may regulate ER morphology (PubMed:16143324). May play a role in vesicle trafficking (PubMed:11511104, PubMed:19289470). {ECO:0000269|PubMed:11511104, ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:19289470, ECO:0000269|PubMed:25447204}.
• Pathway: Cholesterol metabolism - Homo sapiens (human);Exercise-induced Circadian Regulation;Neutrophil degranulation;Metabolism of lipids;Innate Immune System;Immune System;Metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.154

Intolerance Scores

• loftool: 0.691
• rvis_EVS: 0.42
• rvis_percentile_EVS: 76.96

Haploinsufficiency Scores

• pHI: 0.572
• hipred: Y
• hipred_score: 0.550
• ghis: 0.407

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.935

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vapa

Gene ontology

• Biological process: endoplasmic reticulum to Golgi vesicle-mediated transport;endoplasmic reticulum organization;cell death;sphingolipid biosynthetic process;neuron projection development;protein folding in endoplasmic reticulum;positive regulation of I-kappaB kinase/NF-kappaB signaling;neutrophil degranulation;positive regulation by host of viral release from host cell;negative regulation by host of viral genome replication;positive regulation by host of viral genome replication;membrane fusion;protein localization to endoplasmic reticulum;COPII-coated vesicle budding
• Cellular component: Golgi membrane;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;bicellular tight junction;microtubule cytoskeleton;integral component of membrane;nuclear membrane;vesicle;azurophil granule membrane;perinuclear region of cytoplasm;endoplasmic reticulum exit site
• Molecular function: protein binding;microtubule binding;protein domain specific binding;FFAT motif binding;cadherin binding;protein heterodimerization activity