AQP4

aquaporin 4, the group of Aquaporins

Basic information

Region (hg38): 18:26852042-26865771

Links

ENSG00000171885 ∙ NCBI:361 ∙ OMIM:600308 ∙ HGNC:637 ∙ Uniprot:P55087 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuromyelitis optica (Limited), mode of inheritance: Unknown
• intellectual disability (Limited), mode of inheritance: AD
• megalencephalic leukoencephalopathy with subcortical cysts 4, remitting (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting	AR	General	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	Neurologic	37143309

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AQP4 gene.

• Inborn genetic diseases (12 variants)
• not provided (6 variants)
• not specified (1 variants)
• Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AQP4 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					3	3
missense			12	1	1	14
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	13	1	4

Variants in AQP4

This is a list of pathogenic ClinVar variants found in the AQP4 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-26856228-C-T		not specified	Uncertain significance (Oct 16, 2015)
18-26856264-C-T		not specified	Uncertain significance (Jul 28, 2021)
18-26856289-C-T			Benign (Dec 31, 2019)
18-26856296-G-C		not specified	Uncertain significance (Jan 26, 2022)
18-26856310-G-T		not specified	Uncertain significance (Feb 16, 2023)
18-26856364-T-C			Benign (Dec 04, 2018)
18-26856371-T-C		not specified	Uncertain significance (Oct 17, 2023)
18-26856405-G-A		not specified	Uncertain significance (Mar 16, 2022)
18-26856469-G-C		not specified	Uncertain significance (Mar 31, 2023)
18-26856489-T-C		not specified	Uncertain significance (Aug 30, 2022)
18-26860795-T-A		not specified	Uncertain significance (Feb 05, 2024)
18-26860819-G-A		Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting	Uncertain significance (Jan 10, 2022)
18-26860822-C-T		Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting	Pathogenic (Jul 19, 2023)
18-26861158-A-T		not specified	Uncertain significance (Feb 21, 2024)
18-26861165-A-G			Likely benign (Jun 15, 2018)
18-26861177-A-G		not specified	Uncertain significance (Feb 21, 2024)
18-26861191-A-T			Benign (Nov 20, 2018)
18-26862223-C-A		not specified	Uncertain significance (May 04, 2022)
18-26862243-C-G		not specified	Uncertain significance (Sep 13, 2023)
18-26862246-A-G		AQP4-related disorder	Likely benign (Apr 28, 2020)
18-26862297-C-G		Intellectual disability	Likely pathogenic (Nov 01, 2017)
18-26862319-T-C		not specified	Uncertain significance (Aug 17, 2022)
18-26862419-C-A		not specified	Uncertain significance (Aug 01, 2022)
18-26862428-C-A		AQP4-related disorder	Benign (Oct 18, 2019)
18-26862529-A-G		not specified	Conflicting classifications of pathogenicity (Dec 03, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AQP4	protein_coding	protein_coding	ENST00000383168	5	13781

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00229	0.930	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.192	187	180	1.04	0.00000993	2105
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Forms a water-specific channel. Osmoreceptor which regulates body water balance and mediates water flow within the central nervous system.
• Pathway: 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;Passive transport by Aquaporins;Vasopressin regulates renal water homeostasis via Aquaporins;Aquaporin-mediated transport (Consensus)

Recessive Scores

• pRec: 0.345

Intolerance Scores

• loftool: 0.139
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.54

Haploinsufficiency Scores

• pHI: 0.273
• hipred: Y
• hipred_score: 0.605
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.562

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aqp4
• Phenotype: immune system phenotype; renal/urinary system phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: renal water homeostasis;water transport;multicellular organismal water homeostasis;transmembrane transport;cellular response to interferon-gamma
• Cellular component: cytoplasm;plasma membrane;external side of plasma membrane;integral component of membrane;basolateral plasma membrane
• Molecular function: water transmembrane transporter activity;protein binding;water channel activity