Intellectual disability
Gene: VWA8

VWA8 (von Willebrand factor A domain containing 8)
EnsemblGeneIds (GRCh38): ENSG00000102763
EnsemblGeneIds (GRCh37): ENSG00000102763
OMIM: 617509, Gene2Phenotype
VWA8 is in 2 panels

1 review

Ida Ertmanska (Genomics England Curator)

Red List (low evidence)

Comment on list classification: There is one family reported in literature with a biallelic missense variant in VWA8 segregating with a complex neurodevelopmental disorder (PMID: 34660594). Other reports describe individuals with retinitis pigmentosa and monoallelic nonsense variants. Hence, this gene can only be rated Red on Intellectual disability with the current evidence.
Created: 14 Aug 2026, 10:28 a.m. | Last Modified: 14 Aug 2026, 10:28 a.m.

Panel Version: 11.11

PMID: 40638000 Chacon-Camacho et al., 2025
Report of a Mexican patient suffering from retinitis pigmentosa. Classical features of retinal dystrophy were identified, including nyctalopia, peripheral visual field loss, as well as vascular attenuation, and bone spicules on fundus examination. Genetic analysis identified a novel pathogenic c.3069C>G (p.Tyr1023Ter) heterozygous VWA8 variant - 2 hets reported in gnomAD v4.1.1.

PMID: 37012052 Kong et al., 2023
A single family with 11 individuals all presenting initial symptoms of visual defects which later progressed to macular changes, including macular degeneration and dystrophy. Two variants (c.3070G>A;c.4558C>T (p.Gly1024Arg; p.Arg1520Ter)) on the same allele of the VWA8 gene were found to segregate with disease. Expression studies showed reduced protein expression. Zebrafish knockdown model displayed a similar phenotype to that of humans.

PMID: 34660594 Umair et al., 2021
Report of a large consanguineous family of Saudi origin with a complex developmental syndrome: global developmental delay, microcephaly, scoliosis, limbs, and cardiovascular malformations. Affected individuals were homozygous for the VWA8: c.947A>G; p.(Asp316Gly) variant - reported in 29 het individuals in gnomAD v4.1.1 (no homozygotes). Seq method: WES + Sanger confirmation in the parents and sibs.
Functional evidence: zebrafish morpholino approach showed delayed development at an early stage, lack of movement, light sensitivity, severe skeletal deformity such as scoliosis, and facial dysmorphism in vwa8-knockdown fish.

PMID: 42120427 Kong et al., 2026 - Functional evidence - same research group as first patient report in PMID: 37012052
Authors constructed CRISPR Cas9 gene knockout mice with Vwa8 and identified Vwa8 wild-type, heterozygous (Vwa8+/-), and homozygous (Vwa8-/-) mice. Compared to the wild-type mice, the expression of the Hexokinase 2 (HK2) and Pyruvate kinase muscle (PKM) mitochondrial enzymes was reduced in mitochondria isolated from the retinal tissue of the Vwa8+/- and Vwa8-/- mice.
The Vwa8+/- mice showed partial retina pigmentation compared to the wild-type mice, whereas the Vwa8-/- mice had more significant abnormal pigmentation of the fundus. Electroretinogram (ERG) analysis revealed a significant reduction in b-wave amplitudes under photopic conditions in 10-month-old Vwa8+/- mice when compared to wild-type controls, while it was more severe in Vwa8-/- mice with only minimal electrical responses to light stimulation.
Sources: Literature
Created: 14 Aug 2026, 10:26 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

Created: 14 Aug 2026, 10:26 a.m.

Panel version: 11.10

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Red
Literature

Phenotypes

neurodevelopmental disorder, MONDO:0700092

OMIM

617509

Clinvar variants

Variants in VWA8

Penetrance

None

Publications

Panels with this gene

History Filter Activity

14 Aug 2026, Gel status: 1

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: vwa8 has been classified as Red List (Low Evidence).

14 Aug 2026, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ida Ertmanska (Genomics England Curator)

gene: VWA8 was added gene: VWA8 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: VWA8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VWA8 were set to 34660594; 37012052; 40638000; 42120427 Phenotypes for gene: VWA8 were set to neurodevelopmental disorder, MONDO:0700092 Review for gene: VWA8 was set to RED

Intellectual disability Gene: VWA8