GeneBe

AQP5

protein-coding

aquaporin 5, the group of Aquaporins

Gene summary

Aquaporin 5 (AQP5) is a water channel protein. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). Aquaporin 5 plays a role in the generation of saliva, tears and pulmonary secretions. AQP0, AQP2, AQP5, and AQP6 are closely related and all map to 12q13. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001651.4

Inheritance

AD

ClinVar variants

P:6U:49B:19

Top phenotype

Palmoplantar keratoderma, Bothnian type

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr12:49,961,872-49,965,682

External References & Databases

Ensembl (ENSG00000161798)NCBI Gene (362)OMIM (600442)HGNC:638GenCCUniProt (P55064)AlphaFoldClinVar (AQP5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~3.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

palmoplantar keratoderma, Bothnian typeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010849

Submitter: Genomics England PanelApp

nonepidermolytic palmoplantar keratodermaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0006588

Submitter: Orphanet

palmoplantar keratoderma, Bothnian typeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010849

Submitter: PanelApp Australia

palmoplantar keratoderma, Bothnian typeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0010849

Submitter: Ambry Genetics

palmoplantar keratoderma, Bothnian typeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010849

Submitter: Labcorp Genetics (formerly Invitae)

palmoplantar keratoderma, Bothnian typeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0010849

Submitter: G2P

Clinical Genomic Database (CGD)

Palmoplantar keratoderma, Bothnian typeAD

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 23830519Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AQP5 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 46
not providedTotal: 41
Palmoplantar keratoderma, Bothnian typeTotal: 7
AQP5-related disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001651.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
5
clinvar
4
clinvar
 10
missense
4
clinvar
2
clinvar
48
clinvar
6
clinvar
3
clinvar
 63
nonsense
0
start loss
1
clinvar
 1
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total424912774

Highest pathogenic variant AF is 0.00003717297

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001651.4RefSeqNP_001642.14MANE Select
ENST00000293599.7EnsemblENSP00000293599.54MANE Select
ENST00000857226.1EnsemblENSP00000527285.13Standard
ENST00000857226.2EnsemblENSP00000527285.13Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Salivary secretion - Homo sapiens (human)
  • Transport of small molecules
  • Passive transport by Aquaporins
  • Aquaporin-mediated transport
  • Stabilization and expansion of the E-cadherin adherens junction

Biological Process

  • water transport
  • excretion
  • carbon dioxide transport
  • pancreatic juice secretion
  • odontogenesis

Molecular Function

  • protein binding
  • water channel activity
  • identical protein binding

Cellular Component

  • endoplasmic reticulum
  • plasma membrane
  • integral component of plasma membrane
  • microvillus
  • basal plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000293599
Coding exons
4
Length
3812
Individuals with no LoFs
125727
Homozygous LoFs
0
Heterozygous LoFs
16
Defined
125743
p
0.0000636
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.3761561700.9190.00001051671
Missense (PolyPhen)5765.8790.86522633
Synonymous0.2618083.00.9640.00000570607
Loss of Function1.4837.310.4113.11e-780

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000130.00012rare
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000710.000070rare
South Asian0.0000660.000065rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Forms a water-specific channel. Implicated in the generation of saliva, tears, and pulmonary secretions. Required for TRPV4 activation by hypotonicity (PubMed:16571723). Together with TRPV4, controls regulatory volume decrease in salivary epithelial cells (PubMed:16571723). {ECO:0000269|PubMed:16571723}.;
Disease
DISEASE: Keratoderma, palmoplantar, Bothnian type (PPKB) [MIM:600231]: A dermatological disorder characterized by diffuse non-epidermolytic hyperkeratosis of the skin of palms and soles. PPKB is frequently complicated by fungal infections. {ECO:0000269|PubMed:23830519}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.241

Intolerance Scores

LoFtool
0.199
RVIS EVS
-0.34
RVIS percentile EVS
30.37

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.786

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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