AQP3
protein-codingaquaporin 3 (Gill blood group), the group of Aquaporins|Blood group antigens
Gene summary
This gene encodes the water channel protein aquaporin 3. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein, also known as aquaporin 0. Aquaporin 3 is localized at the basal lateral membranes of collecting duct cells in the kidney. In addition to its water channel function, aquaporin 3 has been found to facilitate the transport of nonionic small solutes such as urea and glycerol, but to a smaller degree. It has been suggested that water channels can be functionally heterogeneous and possess water and solute permeation mechanisms. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Hematologic
Intervention: Hematologic
Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AQP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004925.5. 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 | 1 | 1 | 1 | 3 | ||
| missense | 22 | 22 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 25 | 1 | 1 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004916.1 | 6 | MANE Select | |
| Ensembl | ENSP00000297991.4 | 6 | MANE Select | |
| RefSeq | NP_001305073.1 | 5 | Standard | |
| Ensembl | ENSP00000494946.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| aqp3a | Danio rerio | Structure: iridophore Quality: irregular spatial pattern abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vasopressin-regulated water reabsorption - Homo sapiens (human)
- Polythiazide Action Pathway
- Methyclothiazide Action Pathway
- Bumetanide Action Pathway
- Spironolactone Action Pathway
Biological Process
- positive regulation of immune system process
- renal water homeostasis
- water transport
- excretion
- glycerol transport
Molecular Function
- transporter activity
- urea transmembrane transporter activity
- water channel activity
- glycerol channel activity
Cellular Component
- nucleus
- cytoplasm
- plasma membrane
- cell-cell junction
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297991
- Coding exons
- 6
- Length
- 6458
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125737
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.58 | 117 | 176 | 0.664 | 0.0000103 | 1844 |
| Missense (PolyPhen) | 38 | 83.127 | 0.45713 | 855 | ||
| Synonymous | 0.940 | 68 | 78.6 | 0.865 | 0.00000513 | 638 |
| Loss of Function | 2.51 | 4 | 14.2 | 0.281 | 8.02e-7 | 123 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000067 | 0.000062 | rare |
| Latino/Admixed American | 0.00073 | 0.00072 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000037 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Water channel required to promote glycerol permeability and water transport across cell membranes. Acts as a glycerol transporter in skin and plays an important role in regulating SC (stratum corneum) and epidermal glycerol content. Involved in skin hydration, wound healing, and tumorigenesis. Provides kidney medullary collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Slightly permeable to urea and may function as a water and urea exit mechanism in antidiuresis in collecting duct cells. It may play an important role in gastrointestinal tract water transport and in glycerol metabolism (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.339
Intolerance Scores
- LoFtool
- 0.172
- RVIS EVS
- -0.3
- RVIS percentile EVS
- 32.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.514
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |