AQP8

Chr 16

aquaporin 8

Also known as: AQP-8

NCBI Gene: 343 ENSG00000103375 UniProt: O94778 OMIM: 603750

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.12

Clinical Summary— AQP8

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

41 VUS of 50 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.83top 10%

GOF

0.86top 5%

LOF

0.1697th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

VUS41

Likely Benign4

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	41	0	41
Likely Benign	1	3	4
Benign	0	3	3
Total	42	6	48

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

30 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap AQP8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →