GeneBe

AQP2

protein-coding

aquaporin 2, the group of Aquaporins

Gene summary

This gene encodes a water channel protein located in the kidney collecting tubule. It belongs to the MIP/aquaporin family, some members of which are clustered together on chromosome 12q13. Mutations in this gene have been linked to autosomal dominant and recessive forms of nephrogenic diabetes insipidus. [provided by RefSeq, Oct 2008]

MANE transcript

NM_000486.6

Inheritance

AR, SD, AD

ClinVar variants

P:80U:105B:157

Top phenotype

Diabetes insipidus, nephrogenic, 2

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr12:49,950,737-49,958,878

External References & Databases

Ensembl (ENSG00000167580)NCBI Gene (359)OMIM (107777)HGNC:634GenCCUniProt (P41181)AlphaFoldClinVar (AQP2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~8.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nephrogenic diabetes insipidusDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016383

Submitter: Natera

diabetes insipidus, nephrogenic, autosomalSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007451

Submitter: Labcorp Genetics (formerly Invitae)

diabetes insipidus, nephrogenic, autosomalSTRONG

Inheritance Pattern: SD

Disease ID:MONDO:0007451

Submitter: PanelApp Australia

nephrogenic diabetes insipidusSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016383

Submitter: Orphanet

nephrogenic diabetes insipidusDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016383

Submitter: Natera

diabetes insipidus, nephrogenic, autosomalSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007451

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Diabetes insipidus, nephrogenic, 2AD/AR

Manifestation: Endocrine; Renal

Intervention: Endocrine; Renal

Rationale: Individuals can present in infancy with hypernatremia and severe dehydration, and recognition may allow preventive measures and prompt treatment

Refs: 1828422; 8140421; 7524315; 9649557; 16845277Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AQP2 variants in ClinVar

9 Conditions Cataloged
not providedTotal: 271
Diabetes insipidus, nephrogenic, autosomalTotal: 106
Nephrogenic diabetes insipidusTotal: 78
Inborn genetic diseasesTotal: 29
not specifiedTotal: 21
AQP2-related disorderTotal: 11
AQP2-related nephrogenic diabetes insipidusTotal: 2
Hereditary diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000486.6. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
148
clinvar
1
clinvar
 152
missense
4
clinvar
30
clinvar
100
clinvar
8
clinvar
 142
nonsense
6
clinvar
8
clinvar
 14
start loss
1
clinvar
 1
frameshift
8
clinvar
14
clinvar
1
clinvar
 23
splice donor/acceptor (+/-2bp)
1
clinvar
8
clinvar
1
clinvar
 10
Total20601051561342

Highest pathogenic variant AF is 0.00009605657

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000486.6RefSeqNP_000477.14MANE Select
ENST00000199280.4EnsemblENSP00000199280.34MANE Select
ENST00000550862.1EnsemblENSP00000450022.13Standard
ENST00000551526.5EnsemblENSP00000447148.15Standard

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

  • renal water homeostasis
  • renal water transport
  • water transport
  • excretion
  • glycerol transport

Molecular Function

  • water transmembrane transporter activity
  • protein binding
  • glycerol transmembrane transporter activity
  • water channel activity

Cellular Component

  • Golgi apparatus
  • plasma membrane
  • membrane
  • integral component of membrane
  • basolateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000199280
Coding exons
4
Length
8141
Individuals with no LoFs
125710
Homozygous LoFs
0
Heterozygous LoFs
38
Defined
125748
p
0.000151
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.061371770.7760.00001161694
Missense (PolyPhen)5473.8160.73154693
Synonymous-0.4239085.01.060.00000602631
Loss of Function0.25799.870.9125.54e-785

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000130.00012rare
Latino/Admixed American0.000440.00043rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.0000470.000046rare
European (Non-Finnish)0.000120.00011rare
South Asian0.000170.00016rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Forms a water-specific channel that provides the plasma membranes of renal collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient.;
Disease
DISEASE: Diabetes insipidus, nephrogenic, autosomal (ANDI) [MIM:125800]: A disorder caused by the inability of the renal collecting ducts to absorb water in response to arginine vasopressin. Characterized by excessive water drinking (polydipsia), excessive urine excretion (polyuria), persistent hypotonic urine, and hypokalemia. Inheritance can be autosomal dominant or recessive. {ECO:0000269|PubMed:12050236, ECO:0000269|PubMed:12191971, ECO:0000269|PubMed:15509592, ECO:0000269|PubMed:16120822, ECO:0000269|PubMed:16361827, ECO:0000269|PubMed:16845277, ECO:0000269|PubMed:19585583, ECO:0000269|PubMed:19701945, ECO:0000269|PubMed:24944815, ECO:0000269|PubMed:7524315, ECO:0000269|PubMed:8882880, ECO:0000269|PubMed:9048343, ECO:0000269|PubMed:9302264, ECO:0000269|PubMed:9402087, ECO:0000269|PubMed:9550615, ECO:0000269|PubMed:9649557, ECO:0000269|PubMed:9745427}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.606

Intolerance Scores

LoFtool
0.199
RVIS EVS
-0.52
RVIS percentile EVS
21.2

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.741

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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