AQP8

Chr 16

aquaporin 8

Also known as: AQP-8

NCBI Gene: 343 ENSG00000103375 UniProt: O94778

Aquaporin 8 is a water channel protein that facilitates transport of water, hydrogen peroxide, and ammonia across cellular membranes including plasma membranes, mitochondrial membranes, and endoplasmic reticulum in tissues such as liver, intestine, and kidney. The gene shows low constraint against loss-of-function variants (pLI 0.0004, LOEUF 1.12), and no clear disease associations have been established from the available data. The protein plays roles in bile formation, mitochondrial hydrogen peroxide release affecting cholesterol synthesis, and cellular responses to acidosis.

ResearchSummary from RefSeq, UniProt

Aquaporin 8 (AQP8) is a water channel protein. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). Aquaporin 8 mRNA is found in pancreas and colon but not other tissues. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.12

LOEUF

Multiple*

Mechanism· predicted

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?

1.12LOEUF

pLI 0.000

Z-score 1.27

OE 0.60 (0.34–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.57Z-score

OE missense 0.87 (0.76–1.00)

142 obs / 162.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.34–1.12)

0≤0.351.4

Missense OE?0.87 (0.76–1.00)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 7 / 11.7Missense obs/exp: 142 / 162.3Syn Z: 0.67

Background carrier burden — how many people carry a rare variant somewhere in AQP8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

319 rare PASS variants

Rare truncating (LoF)

1 in 540

37 rare PASS variants

Rare synonymous (reference)

1 in 160

148 rare PASS variants

Rare missense and truncating variants are carried at similar rates in AQP8; this gene does not show strong loss-of-function constraint by this measure. 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 170	1 in 610
South Asian	~43k	1 in 130	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 87	1 in 470
European (Finnish)	~27k	1 in 520	none seen
Admixed American	~22k	1 in 120	1 in 830
African / African American	~21k	1 in 150	1 in 1,300
East Asian	~20k	1 in 150	≈ 1 in 4,000
Ashkenazi Jewish	~13k	1 in 470	none seen
Middle Eastern	~2,884	1 in 110	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓