AQP4
protein-codingaquaporin 4, the group of Aquaporins
Gene summary
This gene encodes a member of the aquaporin family of intrinsic membrane proteins that function as water-selective channels in the plasma membranes of many cells. This protein is the predominant aquaporin found in brain and has an important role in brain water homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. Additional isoforms, resulting from the use of alternative in-frame translation initiation codons, have also been described. Recent studies provided evidence for translational readthrough in this gene, and expression of C-terminally extended isoforms via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Jun 2018]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0001071
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0957534
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0019100
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0957534
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AQP4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001650.7. 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 | 3 | 3 | ||||
| missense | 1 | 1 | 36 | 6 | 1 | 45 |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 1 | 1 | 38 | 6 | 4 | 50 |
Highest pathogenic variant AF is 0.0000148713625
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001641.1 | 5 | MANE Select | |
| Ensembl | ENSP00000372654.4 | 5 | MANE Select | |
| RefSeq | NP_001304313.1 | 5 | Standard | |
| RefSeq | NP_001304316.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Bile secretion - Homo sapiens (human)
- Vasopressin-regulated water reabsorption - Homo sapiens (human)
- Spinal Cord Injury
- Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
- Transport of small molecules
Biological Process
- renal water homeostasis
- water transport
- multicellular organismal water homeostasis
- transmembrane transport
- cellular response to interferon-gamma
Molecular Function
- water transmembrane transporter activity
- protein binding
- water channel activity
Cellular Component
- cytoplasm
- plasma membrane
- external side of plasma membrane
- integral component of membrane
- basolateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000383168
- Coding exons
- 5
- Length
- 13781
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125748
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.192 | 187 | 180 | 1.04 | 0.00000993 | 2105 |
| Missense (PolyPhen) | 59 | 68.913 | 0.85616 | 806 | ||
| Synonymous | -0.639 | 71 | 64.5 | 1.10 | 0.00000383 | 660 |
| Loss of Function | 1.59 | 6 | 11.9 | 0.502 | 6.04e-7 | 146 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Forms a water-specific channel. Osmoreceptor which regulates body water balance and mediates water flow within the central nervous system.;
Recessive Scores
- pRec
- 0.345
Intolerance Scores
- LoFtool
- 0.139
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.562
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |