VWA8

Chr 13

von Willebrand factor A domain containing 8

Also known as: KIAA0564, P7BP2, RP97

NCBI Gene: 23078 ENSG00000102763 UniProt: A3KMH1

The VWA8 protein exhibits ATPase activity and localizes to mitochondria and peroxisomes. Mutations cause retinitis pigmentosa 97, which follows autosomal dominant inheritance. The gene shows extremely high constraint against loss-of-function variants (pLI essentially 1.0), indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable ATP hydrolysis activity. Located in mitochondrion and peroxisome. Implicated in retinitis pigmentosa 97. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtRetinitis pigmentosa 97

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.15

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.000

Z-score 0.20

OE 0.98 (0.84–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.21Z-score

OE missense 1.02 (0.97–1.07)

1028 obs / 1009.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.98 (0.84–1.15)

0≤0.351.4

Missense OE?1.02 (0.97–1.07)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 107 / 109.3Missense obs/exp: 1028 / 1009.6Syn Z: -0.29

Background carrier burden — how many people carry a rare variant somewhere in VWA8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 21

2,476 rare PASS variants

Rare truncating (LoF)

1 in 150

465 rare PASS variants

Rare synonymous (reference)

1 in 55

920 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for VWA8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 33	1 in 160
South Asian	~43k	1 in 22	1 in 100
Remaining (unassigned)	~30k	1 in 17	1 in 170
European (Finnish)	~27k	1 in 75	1 in 1,200
Admixed American	~22k	1 in 22	1 in 150
African / African American	~21k	1 in 21	1 in 120
East Asian	~20k	1 in 28	1 in 150
Ashkenazi Jewish	~13k	1 in 150	1 in 370
Middle Eastern	~2,884	1 in 23	1 in 96

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 41 of 45 coding exons well covered in gnomAD exomes; exons 1, 2, 7, 24 marginal. Genomes: 44 of 45 (exon 18 below).? see exons ↓