AQP1

protein-coding

aquaporin 1 (Colton blood group), the group of Blood group antigens|Aquaporins

Gene summary

This gene encodes a small integral membrane protein with six bilayer spanning domains that functions as a water channel protein. This protein permits passive transport of water along an osmotic gradient. This gene is a possible candidate for disorders involving imbalance in ocular fluid movement. [provided by RefSeq, Aug 2016]

Previous symbols:

MANE transcript

NM_198098.4

Inheritance

AD, BG

ClinVar variants

P:3U:40B:27

Top phenotype

Blood group, Colton

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr7:30,911,853-30,925,517

External References & Databases

Ensembl (ENSG00000240583)

Transcript & Mutation Effects

hg38 • Region Span ~13.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pulmonary arterial hypertensionLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0015924

Submitter: Ambry Genetics

pulmonary arterial hypertensionLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0015924

Submitter: ClinGen

AQP1 was first reported in relation to pulmonary arterial hypertension (PAH) in 2018 (Gräf et al., PMID: 30578397). Case-control analysis of genome sequence data from 838 PAH patients (without variants in other known PAH genes) and 6385 controls identified five rare predicted deleterious missense variants in nine unrelated individuals. Three additional rare missense variants were identified in a Han Chinese IPAH cohort (PMID: 30578397) Expression of AQP1 was demonstrated in healthy donor lung and PAH lung endothelium and plexiform lesions (PMID: 30578397) but no functional effects of patient variants have been reported. In mice, homozygosity for Aqp1 null alleles resulted in attenuated hypoxic pulmonary hypertension (PMID: 30580569, 28409279). Currently, only heterozygous missense variants are considered potentially disease relevant. In summary, there is limited evidence to support this gene-disease relationship. The classification was approved by the ClinGen Pulmonary Hypertension Gene Curation Expert Panel on 07/01/2021 (SOP Version 8). The gene-disease relationship was re-evaluated on 10/09/2025 by the ClinGen PH Gene Curation Expert Panel (SOP v11). A recurrent missense variant identified independently in both PMID: 30578397 and PMID: 30578397 during initial curation was identified in two additional PAH families, Spanish (PMID: 35627312) and German (PMID: 35346192) where it co-seggregated with the disease. No further experimental evidence was identified. As a result of this re-evaluation, the classification did not change.

pulmonary arterial hypertensionMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0015924

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Blood group, ColtonBG

Manifestation: Hematologic

Intervention: Hematologic

Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Refs: 7521540; 7521882; 11606828; 11463012; 11773634

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AQP1 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 49

not specifiedTotal: 36

AQP1-related disorderTotal: 6

Colton-null phenotypeTotal: 1

AQP1-related pulmonary hypertensionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198098.4. 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				16 clinvar	3 clinvar	19
missense	3 clinvar		38 clinvar	6 clinvar	2 clinvar	49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	3	0	40	22	5	70

Highest pathogenic variant AF is 0.00001859395

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_198098.4	RefSeq	NP_932766.1	4	MANE Select
ENST00000311813.11	Ensembl	ENSP00000311165.4	4	MANE Select
NM_001329872.2	RefSeq	NP_001316801.1	5	Standard
ENST00000409611.1	Ensembl	ENSP00000387178.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
aqp1a.1	Danio rerio	Structure: vH ionocyte Quality: decreased process quality abnormal

Gene / Model

Organism

Observed Phenotype

aqp1a.1

Danio rerio

Structure: vH ionocyte

Quality: decreased process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Bile secretion - Homo sapiens (human)
Proximal tubule bicarbonate reclamation - Homo sapiens (human)
Renin secretion - Homo sapiens (human)
Polythiazide Action Pathway
Methyclothiazide Action Pathway

Biological Process

renal water homeostasis
renal water transport
potassium ion transport
water transport
cell volume homeostasis

Molecular Function

intracellular cGMP-activated cation channel activity
potassium channel activity
water transmembrane transporter activity
protein binding
ammonium transmembrane transporter activity

Cellular Component

nucleus
cytoplasm
plasma membrane
integral component of plasma membrane
brush border

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311813
Coding exons: 4
Length: 72122
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125748
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.544	156	176	0.885	0.0000119	1730
Missense (PolyPhen)		73	87.404	0.8352		867
Synonymous	-0.851	92	82.2	1.12	0.00000654	592
Loss of Function	1.81	3	8.80	0.341	4.81e-7	82

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Forms a water-specific channel that provides the plasma membranes of red cells and kidney proximal tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. {ECO:0000269|PubMed:1373524}.;

Recessive Scores

pRec: 0.406

Intolerance Scores

LoFtool: 0.111
RVIS EVS: 0.04
RVIS percentile EVS: 57.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.755

Gene Damage Prediction

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