AQP2

aquaporin 2, the group of Aquaporins

Basic information

Region (hg38): 12:49950736-49958878

Links

ENSG00000167580 ∙ NCBI:359 ∙ OMIM:107777 ∙ HGNC:634 ∙ Uniprot:P41181 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephrogenic diabetes insipidus (Supportive), mode of inheritance: AD
• diabetes insipidus, nephrogenic, autosomal (Strong), mode of inheritance: AR
• diabetes insipidus, nephrogenic, autosomal (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diabetes insipidus, nephrogenic, 2	AD/AR	Endocrine; Renal	Individuals can present in infancy with hypernatremia and severe dehydration, and recognition may allow preventive measures and prompt treatment	Endocrine; Renal	1828422; 8140421; 7524315; 9649557; 16845277

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AQP2 gene.

• not provided (209 variants)
• Diabetes insipidus, nephrogenic, autosomal (129 variants)
• Nephrogenic diabetes insipidus (32 variants)
• Inborn genetic diseases (11 variants)
• not specified (6 variants)
• Hereditary disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AQP2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	113	3	117
missense	7	8	21	3		39
nonsense	8	2				10
start loss						0
frameshift	7	2				9
inframe indel						0
splice donor/acceptor (+/-2bp)	1	5				6
splice region			2	8	1	11
non coding			52	13	35	100
Total	23	17	74	129	38

Highest pathogenic variant AF is 0.0000723

Variants in AQP2

This is a list of pathogenic ClinVar variants found in the AQP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-49950738-G-A		Diabetes insipidus, nephrogenic, autosomal	Uncertain significance (Jan 13, 2018)
12-49950756-G-A		Diabetes insipidus, nephrogenic, autosomal	Uncertain significance (Jan 13, 2018)
12-49950756-G-T		Diabetes insipidus, nephrogenic, autosomal	Uncertain significance (Jan 13, 2018)
12-49950766-G-A		Diabetes insipidus, nephrogenic, autosomal	Uncertain significance (Jan 12, 2018)
12-49950771-C-T		Diabetes insipidus, nephrogenic, autosomal	Uncertain significance (Mar 21, 2022)
12-49950772-G-A		Diabetes insipidus, nephrogenic, autosomal	Benign (Jan 13, 2018)
12-49950815-C-T		Diabetes insipidus, nephrogenic, autosomal	Uncertain significance (Jan 13, 2018)
12-49950833-G-T		Diabetes insipidus, nephrogenic, autosomal	Pathogenic (May 31, 2019)
12-49950839-G-A			Likely benign (Jan 25, 2023)
12-49950843-C-T			Uncertain significance (Jun 23, 2022)
12-49950844-G-A		Inborn genetic diseases	Uncertain significance (Oct 16, 2022)
12-49950850-T-C			Uncertain significance (Oct 17, 2022)
12-49950854-C-G			Likely benign (Nov 24, 2023)
12-49950854-C-T			Likely benign (Apr 18, 2023)
12-49950862-G-A		Diabetes insipidus, nephrogenic, autosomal	Uncertain significance (Jan 13, 2018)
12-49950863-G-A			Likely benign (Oct 09, 2023)
12-49950869-G-A		not specified • Diabetes insipidus, nephrogenic, autosomal • Nephrogenic diabetes insipidus	Benign/Likely benign (Jan 31, 2024)
12-49950872-C-T			Likely benign (Nov 24, 2022)
12-49950875-A-G			Likely benign (Oct 16, 2023)
12-49950881-C-T			Likely benign (Sep 14, 2021)
12-49950890-A-C			Likely benign (Jul 26, 2023)
12-49950890-A-G			Likely benign (Mar 12, 2022)
12-49950892-T-C			Uncertain significance (Sep 16, 2018)
12-49950893-C-G			Likely benign (Jan 26, 2023)
12-49950893-C-T			Likely benign (Oct 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AQP2	protein_coding	protein_coding	ENST00000199280	4	8141

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000249	0.309	125710	0	38	125748	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.06	137	177	0.776	0.0000116	1694
Missense in Polyphen		54	73.816	0.73154		693
Synonymous	-0.423	90	85.0	1.06	0.00000602	631
Loss of Function	0.257	9	9.87	0.912	5.54e-7	85

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000563	0.000559
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.000121	0.000114
Middle Eastern	0.000109	0.000109
South Asian	0.000174	0.000163
Other	0.00	0.00

dbNSFP

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.
• Pathway: Vasopressin-regulated water reabsorption - Homo sapiens (human);Polythiazide Action Pathway;Methyclothiazide Action Pathway;Bumetanide Action Pathway;Spironolactone Action Pathway;Eplerenone Action Pathway;Triamterene Action Pathway;Amiloride Action Pathway;Ethacrynic Acid Action Pathway;Quinethazone Action Pathway;Bendroflumethiazide Action Pathway;Chlorthalidone Action Pathway;Trichlormethiazide Action Pathway;Iminoglycinuria;Lysinuric Protein Intolerance;Blue diaper syndrome;Lysinuric protein intolerance (LPI);Cystinuria;Indapamide Action Pathway;Furosemide Action Pathway;Torsemide Action Pathway;Hartnup Disorder;Glucose Transporter Defect (SGLT2);Kidney Function;Glucose Transporter Defect (SGLT2);Metolazone Action Pathway;Hydrochlorothiazide Action Pathway;Cyclothiazide Action Pathway;Hydroflumethiazide Action Pathway;Chlorothiazide Action Pathway;Transport of small molecules;Passive transport by Aquaporins;Vasopressin regulates renal water homeostasis via Aquaporins;Aquaporin-mediated transport (Consensus)

Recessive Scores

• pRec: 0.606

Intolerance Scores

• loftool: 0.199
• rvis_EVS: -0.52
• rvis_percentile_EVS: 21.2

Haploinsufficiency Scores

• pHI: 0.227
• hipred: Y
• hipred_score: 0.665
• ghis: 0.487

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.741

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Aqp2
• Phenotype: homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype

Gene ontology

• Biological process: renal water homeostasis;renal water transport;water transport;excretion;glycerol transport;cellular response to water deprivation;transmembrane transport;cellular response to copper ion;cellular response to mercury ion;metanephric collecting duct development
• Cellular component: Golgi apparatus;plasma membrane;membrane;integral component of membrane;basolateral plasma membrane;apical plasma membrane;transport vesicle membrane;recycling endosome;extracellular exosome
• Molecular function: water transmembrane transporter activity;protein binding;glycerol transmembrane transporter activity;water channel activity