VAPB

VAMP associated protein B and C

Basic information

Region (hg38): 20:58389229-58451101

Links

ENSG00000124164

∙ NCBI:9217 ∙ OMIM:605704 ∙ HGNC:12649 ∙ Uniprot:O95292 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

amyotrophic lateral sclerosis type 8 (Strong), mode of inheritance: AD
amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
adult-onset proximal spinal muscular atrophy, autosomal dominant (Supportive), mode of inheritance: AD
amyotrophic lateral sclerosis type 8 (Strong), mode of inheritance: AD
amyotrophic lateral sclerosis type 8 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amyotrophic lateral sclerosis 8; Spinal muscular atrophy, late-onset, Finkel type	AD	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	Neurologic	15372378; 18322265; 20940299; 20577002

ClinVar

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

Amyotrophic_lateral_sclerosis_type_8 (195 variants)
Adult-onset_proximal_spinal_muscular_atrophy,_autosomal_dominant (194 variants)
Inborn_genetic_diseases (56 variants)
not_provided (29 variants)
VAPB-related_disorder (15 variants)
not_specified (6 variants)
Spinal_Muscular_Atrophy,_Dominant (1 variants)
Amyotrophic_Lateral_Sclerosis,_Dominant (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VAPB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004738.5. 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				35 clinvar	3 clinvar	38
missense	2 clinvar		121 clinvar	10 clinvar		133
nonsense						0
start loss						0
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	2	0	128	45	3

Highest pathogenic variant AF is 0.00000136809

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VAPB	protein_coding	protein_coding	ENST00000475243	6	61980

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.581	0.417	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	94	135	0.696	0.00000727	1598
Missense in Polyphen		23	52.86	0.43511		615
Synonymous	0.681	44	50.1	0.878	0.00000282	459
Loss of Function	2.56	2	11.3	0.178	5.63e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Participates in the endoplasmic reticulum unfolded protein response (UPR) by inducing ERN1/IRE1 activity. Involved in cellular calcium homeostasis regulation. {ECO:0000269|PubMed:16891305, ECO:0000269|PubMed:20940299, ECO:0000269|PubMed:22131369}.;
Disease: DISEASE: Spinal muscular atrophy, proximal, adult, autosomal dominant (SMAPAD) [MIM:182980]: A form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAPAD is characterized by proximal muscle weakness that begins in the lower limbs and then progresses to upper limbs, onset in late adulthood (after third decade) and a benign course. Most of the patients remain ambulatory 10 to 40 years after clinical onset. {ECO:0000269|PubMed:15372378}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Cholesterol metabolism - Homo sapiens (human);Metabolism of lipids;Metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

pRec: 0.203

Intolerance Scores

loftool: 0.282
rvis_EVS: -0.01
rvis_percentile_EVS: 53.19

Haploinsufficiency Scores

pHI: 0.578
hipred: Y
hipred_score: 0.710
ghis: 0.637

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Vapb
Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype;

Zebrafish Information Network

Gene name: vapb
Affected structure: motor neuron
Phenotype tag: abnormal
Phenotype quality: morphology

Gene ontology

Biological process: cellular calcium ion homeostasis;endoplasmic reticulum to Golgi vesicle-mediated transport;endoplasmic reticulum organization;modulation by virus of host morphology or physiology;sphingolipid biosynthetic process;endoplasmic reticulum unfolded protein response;IRE1-mediated unfolded protein response;positive regulation of viral genome replication;COPII-coated vesicle budding
Cellular component: Golgi membrane;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;integral component of membrane;endoplasmic reticulum exit site
Molecular function: protein binding;microtubule binding;enzyme binding;FFAT motif binding;protein homodimerization activity;cadherin binding;protein heterodimerization activity;beta-tubulin binding