AQP4 aquaporin 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AQP4provided by HGNC
Official Full Name: aquaporin 4provided by HGNC
Primary source: HGNC:HGNC:637
See related: Ensembl:ENSG00000171885 MIM:600308; AllianceGenome:HGNC:637
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MIWC; MLC4; WCH4; hAQP4
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]
Expression: Biased expression in brain (RPKM 248.2) and lung (RPKM 72.5) See more
Orthologs: mouse all
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Genomic context

Location:: 18q11.2

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	18	NC_000018.10 (26852038..26865803, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	18	NC_060942.1 (27046091..27059856, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (24432002..24445767, complement)

Chromosome 18 - NC_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder.
Title: Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder.
B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4.
Title: B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4.
Aquaporin-4 and Parkinson's Disease.
Title: Aquaporin-4 and Parkinson's Disease.
Non-coding RNAs and Aquaporin 4: Their Role in the Pathogenesis of Neurological Disorders.
Title: Non-coding RNAs and Aquaporin 4: Their Role in the Pathogenesis of Neurological Disorders.
Glymphatic system and aquaporin-4 in epilepsy.
Title: Glymphatic system and aquaporin‑4 in epilepsy.
The Expression and Role of Aquaporin 4 in Colon Cancer.
Title: The Expression and Role of Aquaporin 4 in Colon Cancer.
Renal dysfunction in AQP4 NMOSD and MS; a potential predictor of relapse and prognosis.
Title: Renal dysfunction in AQP4 NMOSD and MS; a potential predictor of relapse and prognosis.
Readthrough isoform of aquaporin-4 (AQP4) as a therapeutic target for Alzheimer's disease and other proteinopathies.
Title: Readthrough isoform of aquaporin-4 (AQP4) as a therapeutic target for Alzheimer's disease and other proteinopathies.
Barriers to access and unmet needs to neuromyelitis optica spectrum disorders care in an Argentinean cohort.
Title: Barriers to access and unmet needs to neuromyelitis optica spectrum disorders care in an Argentinean cohort.
Estimated prevalence of AQP4 positive neuromyelitis optica spectrum disorder and MOG antibody associated disease in Sao Paulo, Brazil.
Title: Estimated prevalence of AQP4 positive neuromyelitis optica spectrum disorder and MOG antibody associated disease in São Paulo, Brazil.

Submit: New GeneRIF Correction See all GeneRIFs (307)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MedGen: C5830628 OMIM: 620448 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D18S1195 (e-PCR)
- UniSTS:42497

D18S941E (e-PCR)
- UniSTS:150533

AQP4_717 (e-PCR)
- UniSTS:277005

AQP4_V79 (e-PCR)
- UniSTS:277005

RH25921 (e-PCR)
- UniSTS:85531

D18S1223 (e-PCR)
- UniSTS:70969

RH18229 (e-PCR)
- UniSTS:45891

A006W40 (e-PCR)
- UniSTS:3912

SHGC-36589 (e-PCR)
- UniSTS:83072

RH121996 (e-PCR)
- UniSTS:132249

Aqp4 (e-PCR), detects polymorphism
- UniSTS:209565

WI-13598 (e-PCR)
- UniSTS:77734

A002Q03 (e-PCR)
- UniSTS:56496

D18S1223 (e-PCR)
- UniSTS:79853

WI-21214 (e-PCR)
- UniSTS:3054

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables water channel activity	EXP Inferred from Experiment more info	PubMed
enables water channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables water channel activity	IDA Inferred from Direct Assay more info	PubMed
enables water channel activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular response to type II interferon	IDA Inferred from Direct Assay more info	PubMed
involved_in cerebrospinal fluid circulation	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular water homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular water homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in multicellular organismal-level water homeostasis	IEP Inferred from Expression Pattern more info	PubMed
involved_in multicellular organismal-level water homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein homotetramerization	IDA Inferred from Direct Assay more info	PubMed
involved_in renal water homeostasis	TAS Traceable Author Statement more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in water transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in water transport	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in astrocyte end-foot	ISS Inferred from Sequence or Structural Similarity more info
is_active_in basolateral plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in basolateral plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in sarcolemma	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: aquaporin-4

Names: aquaporin type4; mercurial-insensitive water channel

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029560.1 RefSeqGene

Range

5046..18710

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001317384.3 → NP_001304313.1 aquaporin-4 isoform M1x

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as hMIWC2) represents the predominant transcript and encodes four isoforms, resulting from the use of two alternative in-frame translation initiation codons and two alternative in-frame translation termination codons. This RefSeq represents the longest, C-terminally extended isoform (M1x, also known as M1ex), which results from the use of the upstream AUG start codon and readthrough of the upstream UGA stop codon to the downstream UAA stop codon. As the UGA stop codon has been reported to specify several alternative amino acids (tryptophan, cysteine, arginine and serine), its location in this isoform is denoted by an 'X'.

Source sequence(s)

AC018371, AK222684, BU687682, DA244620, DT220791, HQ901095

Consensus CDS

CCDS92445.1

UniProtKB/TrEMBL

A0A5F9ZHR4, Q53H97

Related

ENSP00000500598.2, ENST00000672981.2

Conserved Domains (1) summary

pfam00230
Location:31 → 248

MIP; Major intrinsic protein
NM_001317387.3 → NP_001304316.1 aquaporin-4 isoform delta4

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an in-frame coding exon compared to variant 1, and encodes a shorter isoform (delta4) missing an internal protein segment compared to isoform M1. This isoform exhibits no water transport properties, and downregulates the expression and water channel activity of isoform M1; thus, appears to function as a regulator of water permeability (PMID:24356448).

Source sequence(s)

AC018371, AK222684, BU687682, DA244620, DT220791, HQ901095

Consensus CDS

CCDS82244.1

UniProtKB/TrEMBL

Q53H97, V9PBN7

Related

ENSP00000502364.1, ENST00000675739.1

Conserved Domains (1) summary

cl00200
Location:31 → 221

MIP; Major intrinsic protein (MIP) superfamily. Members of the MIP superfamily function as membrane channels that selectively transport water, small neutral molecules, and ions out of and between cells. The channel proteins share a common fold: the N-terminal ...
NM_001364286.1 → NP_001351215.1 aquaporin-4 isoform M23

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as hMIWC2) represents the predominant transcript and encodes four isoforms, resulting from the use of two alternative in-frame translation initiation codons and two alternative in-frame translation termination codons. This RefSeq represents isoform M23, which results from the use of the downstream in-frame AUG start codon and the upstream UGA stop codon. Isoform M23 has a shorter N-terminus compared to isoform M1. An alternatively spliced transcript variant (NM_004028.4) encodes the same isoform.

Source sequence(s)

AC018371, AK222684, BU687682, DA244620, DT220791, HQ901095

Consensus CDS

CCDS58617.1

UniProtKB/TrEMBL

Q53H97

Conserved Domains (1) summary

pfam00230
Location:9 → 226

MIP; Major intrinsic protein
NM_001364287.1 → NP_001351216.1 aquaporin-4 isoform M23x

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as hMIWC2) represents the predominant transcript and encodes four isoforms, resulting from the use of two alternative in-frame translation initiation codons and two alternative in-frame translation termination codons. This RefSeq represents a C-terminally extended isoform (M23x, also known as M23ex), which results from the use of the downstream in-frame AUG start codon and readthrough of the upstream UGA stop codon to the downstream UAA stop codon. As the UGA stop codon has been reported to specify several alternative amino acids (tryptophan, cysteine, arginine and serine), its location in this isoform is denoted by an 'X'. An alternatively spliced transcript variant (NM_001364289.1) encodes the same isoform.

Source sequence(s)

AC018371, AK222684, BU687682, DA244620, DT220791, HQ901095

UniProtKB/TrEMBL

Q53H97

Conserved Domains (1) summary

pfam00230
Location:9 → 226

MIP; Major intrinsic protein
NM_001364289.2 → NP_001351218.1 aquaporin-4 isoform M23x

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as hMIWC1) is alternatively spliced at the 5' end, which causes translation initiation from an in-frame, downstream start codon, compared to variant 1. Variant 2 encodes two isoforms, resulting from the use of alternative in-frame translation termination codons. The encoded isoform (M23x, also known as M23ex), which results from readthrough of the upstream UGA stop codon to the downstream UAA stop codon, has a shorter N-terminus and a longer C-terminus compared to isoform M1. As the UGA stop codon has been reported to specify several alternative amino acids (tryptophan, cysteine, arginine and serine), its location in isoform M23x is denoted by an 'X'. This isoform is the same as that represented in NM_001364287.1.

Source sequence(s)

AC018371, BC030745, HQ901095, U34845

UniProtKB/TrEMBL

Q53H97

Conserved Domains (1) summary

pfam00230
Location:9 → 226

MIP; Major intrinsic protein
NM_001650.7 → NP_001641.1 aquaporin-4 isoform M1

See identical proteins and their annotated locations for NP_001641.1

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as hMIWC2) represents the predominant transcript and encodes four isoforms, resulting from the use of two alternative in-frame translation initiation codons and two alternative in-frame translation termination codons. This RefSeq represents isoform M1, which results from the use of the upstream AUG start codon and the upstream UGA stop codon.

Source sequence(s)

AC018371, AK222684, BU687682, DA244620, DT220791, HQ901095

Consensus CDS

CCDS11889.1

UniProtKB/Swiss-Prot

P55087, P78564

UniProtKB/TrEMBL

F1DSG4, Q53H97

Related

ENSP00000372654.4, ENST00000383168.9

Conserved Domains (1) summary

pfam00230
Location:31 → 248

MIP; Major intrinsic protein
NM_004028.5 → NP_004019.1 aquaporin-4 isoform M23

See identical proteins and their annotated locations for NP_004019.1

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as hMIWC1) is alternatively spliced at the 5' end, which causes translation initiation from an in-frame, downstream start codon, compared to variant 1. Variant 2 encodes two isoforms, resulting from the use of alternative in-frame translation termination codons. The encoded isoform (M23), which results from the use of the upstream UGA stop codon, has a shorter N-terminus compared to isoform M1. This isoform is the same as that represented in NM_001364286.1.

Source sequence(s)

AC018371, BC030745, HQ901095, U34845

Consensus CDS

CCDS58617.1

UniProtKB/TrEMBL

Q53H97

Related

ENSP00000462597.1, ENST00000581374.5

Conserved Domains (1) summary

pfam00230
Location:9 → 226

MIP; Major intrinsic protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000018.10 Reference GRCh38.p14 Primary Assembly

Range

26852038..26865803 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011525942.4 → XP_011524244.1 aquaporin-4 isoform X1

UniProtKB/TrEMBL

Q53H97

Conserved Domains (1) summary

pfam00230
Location:24 → 241

MIP; Major intrinsic protein