VWA1

von Willebrand factor A domain containing 1, the group of Fibronectin type III domain containing

Basic information

Region (hg38): 1:1434861-1442882

Links

ENSG00000179403 ∙ NCBI:64856 ∙ OMIM:611901 ∙ HGNC:30910 ∙ Uniprot:Q6PCB0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronopathy, distal hereditary motor, autosomal recessive 5 (Supportive), mode of inheritance: AR
• neuronopathy, distal hereditary motor, autosomal recessive 7 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuronopathy, distal hereditary motor, autosomal recessive 7	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	Musculoskeletal; Neurologic	33459760; 33559681

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VWA1 gene.

• not_specified (114 variants)
• not_provided (33 variants)
• Neuronopathy,_distal_hereditary_motor,_autosomal_recessive_7 (17 variants)
• Neuromuscular_disease (6 variants)
• VWA1-related_disorder (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VWA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022834.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	9	3	14
missense		1	111	6	2	120
nonsense	1	2				3
start loss						0
frameshift	3	9	2			14
splice donor/acceptor (+/-2bp)		1				1
Total	4	13	115	15	5

Highest pathogenic variant AF is 0.0009313573

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VWA1	protein_coding	protein_coding	ENST00000476993	3	8022

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00529	0.901	125110	0	34	125144	0.000136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.150	219	213	1.03	0.0000149	2681
Missense in Polyphen		78	74.142	1.052		953
Synonymous	0.320	100	104	0.960	0.00000800	1052
Loss of Function	1.43	5	9.86	0.507	5.95e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000384	0.000369
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000549	0.0000544
Finnish	0.0000484	0.0000462
European (Non-Finnish)	0.000132	0.000124
Middle Eastern	0.0000549	0.0000544
South Asian	0.000298	0.000294
Other	0.000336	0.000327

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes matrix assembly. {ECO:0000250|UniProtKB:Q8R2Z5}.
• Pathway: Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (Consensus)

Recessive Scores

• pRec: 0.142

Haploinsufficiency Scores

• pHI: 0.159
• hipred: N
• hipred_score: 0.180
• ghis: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0208

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vwa1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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)

Gene ontology

• Biological process: growth plate cartilage chondrocyte morphogenesis;extracellular matrix organization;post-translational protein modification;cellular protein metabolic process;behavioral response to pain
• Cellular component: basement membrane;interstitial matrix;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: extracellular matrix structural constituent;identical protein binding