VWA1

protein-coding

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

Gene summary

VWA1 belongs to the von Willebrand factor (VWF; MIM 613160) A (VWFA) domain superfamily of extracellular matrix proteins and appears to play a role in cartilage structure and function (Fitzgerald et al., 2002 [PubMed 12062410]).[supplied by OMIM, Nov 2010]

MANE transcript

NM_022834.5

Inheritance

ClinVar variants

P:21U:132B:32

Top phenotype

Neuronopathy, distal hereditary motor, autosomal recessive 7

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr1:1,434,861-1,442,882

External References & Databases

Ensembl (ENSG00000179403)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neuronopathy, distal hereditary motor, autosomal recessive 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030977

Submitter: PanelApp Australia

neuronopathy, distal hereditary motor, autosomal recessive 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030977

Submitter: Labcorp Genetics (formerly Invitae)

neuronopathy, distal hereditary motor, autosomal recessive 5SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013947

Submitter: Orphanet

Clinical Genomic Database (CGD)

Neuronopathy, distal hereditary motor, autosomal recessive 7AR

Manifestation: Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 33459760; 33559681

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VWA1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 145

not providedTotal: 46

Neuronopathy, distal hereditary motor, autosomal recessive 7Total: 21

Neuromuscular diseaseTotal: 6

VWA1-related disorderTotal: 3

Zygodactyly type 1Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022834.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	16 clinvar	5 clinvar	24
missense		2 clinvar	126 clinvar	10 clinvar	1 clinvar	139
nonsense	1 clinvar	2 clinvar				3
start loss						0
frameshift	3 clinvar	12 clinvar	2 clinvar			17
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	4	17	132	26	6	185

Highest pathogenic variant AF is 0.0009313573

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022834.5	RefSeq	NP_073745.2	3	MANE Select
ENST00000476993.2	Ensembl	ENSP00000417185.1	3	MANE Select
NM_199121.3	RefSeq	NP_954572.2	2	Standard
ENST00000338660.5	Ensembl	ENSP00000423404.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

growth plate cartilage chondrocyte morphogenesis
extracellular matrix organization
post-translational protein modification
cellular protein metabolic process
behavioral response to pain

Molecular Function

extracellular matrix structural constituent
identical protein binding

Cellular Component

basement membrane
interstitial matrix
extracellular space
endoplasmic reticulum lumen
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000476993
Coding exons: 3
Length: 8022
Individuals with no LoFs: 125110
Homozygous LoFs: 0
Heterozygous LoFs: 34
Defined: 125144
p: 0.000136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.150	219	213	1.03	0.0000149	2681
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.00030	0.00029	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes matrix assembly. {ECO:0000250|UniProtKB:Q8R2Z5}.;

Recessive Scores

pRec: 0.142

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0208

Gene Damage Prediction

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