AQP5 (Aquaporin-5) variants and mutations
AQP5 (also known as Aquaporin-5) is a human protein-coding gene encoding an aquaporin-5 protein. It supports fluid secretion in salivary, lacrimal, airway, and other exocrine tissues by facilitating transcellular water movement. Dominant pathogenic variants can cause palmoplantar keratoderma, reflecting an additional role in epidermal homeostasis. This analysis covers 636 AQP5 variants and mutations. Of these, 88% have computational variant effect predictions. Disease context includes Non-epidermolytic palmoplantar keratoderma, Palmoplantar keratoderma, and epidermolytic palmoplantar keratoderma, 1. Example AQP5 variants include K2R, K2N, and K2K.
Variant analysis overview
- Gene: AQP5
- Protein: Aquaporin-5
- UniProt accession: P55064
- Organism: Homo sapiens
- Variants analyzed: 636
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 337 unspecified-consequence records; 160 missense variants; 20 frameshift variants; 107 synonymous variants; 3 stop-gained variants; 4 in-frame deletions; 2 in-frame insertions; 3 splice-region variants
- Prediction scores: 560 variants have prediction scores (88% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Non-epidermolytic palmoplantar keratoderma, Palmoplantar keratoderma, epidermolytic palmoplantar keratoderma, 1, hereditary palmoplantar keratoderma, diffuse nonepidermolytic palmoplantar keratoderma, neoplasm, breast carcinoma, breast cancer, synovial sarcoma, gastric cancer, Cone rod dystrophy, hepatocellular carcinoma.
Protein structure and variant hotspots
- Protein features: 6 transmembrane segments; 2 post-translational modification sites.
- Structural context: 303 variants have structural context.
- PTM context: 9 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable AQP5 variants
Examples include K2R, K2N, K2K, K3R, K3K, E4G, E4K, E4V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- K2R (p.Lys2Arg), Ensembl rs1947428608, REVEL 0.26, CADD 17.80
- K2N (p.Lys2Asn), gnomAD 12-49962023-G-T, REVEL 0.24, CADD 22.00
- K2K (p.Lys2Lys), rs1947428637, gnomAD 12-49962023-G-A, CADD 12.90
- K3R (p.Lys3Arg), gnomAD 12-49962023-GA-G, CADD 22.70
- K3K (p.Lys3Lys), gnomAD 12-49962026-G-A, CADD 11.20
- E4G (p.Glu4Gly), TOPMed rs1414511990, gnomAD rs1414511990, REVEL 0.66, CADD 28.00
- E4K (p.Glu4Lys), TOPMed rs1947428679, gnomAD rs1947428679, REVEL 0.77, CADD 26.40
- E4V (p.Glu4Val), TOPMed rs1414511990, gnomAD rs1414511990, REVEL 0.75, CADD 27.80, Uncertain significance, not provided
- E4D (p.Glu4Asp), gnomAD 12-49962029-G-T, REVEL 0.41, CADD 20.60
- E4E (p.Glu4Glu), rs555099046, gnomAD 12-49962029-G-A, CADD 9.14
- V5G (p.Val5Gly), Ensembl rs1592820431, REVEL 0.47, CADD 23.10
- V5L (p.Val5Leu), TOPMed rs1947428790, gnomAD rs1947428790, REVEL 0.27, CADD 0.27
- C6F (p.Cys6Phe), gnomAD rs1359109751, REVEL 0.22, CADD 16.90
- C6W (p.Cys6Trp), ExAC rs747845858, TOPMed rs747845858, gnomAD rs747845858, REVEL 0.35, CADD 14.00
- C6Y (p.Cys6Tyr), gnomAD 12-49962034-G-A, REVEL 0.21, CADD 16.10
- S7P (p.Ser7Pro), gnomAD 12-49962036-T-C, REVEL 0.52, CADD 22.50
- S7C (p.Ser7Cys), gnomAD 12-49962037-C-G, REVEL 0.49, CADD 23.60
- S7S (p.Ser7Ser), gnomAD 12-49962038-C-T, CADD 4.19
- V8A (p.Val8Ala), TOPMed rs1947429024
- V8L (p.Val8Leu), NCI-TCGA Cosmic COSV5222, NCI-TCGA Cosmic COSV5223, REVEL 0.24, CADD 0.25, Variant assessed as somatic; moderate impact.
- V8M (p.Val8Met), ExAC rs758120085, TOPMed rs758120085, gnomAD rs758120085, REVEL 0.14, CADD 2.09, Uncertain significance, not provided
- V8V (p.Val8Val), gnomAD 12-49962041-G-A, CADD 1.90
- A9T (p.Ala9Thr), NCI-TCGA TCGA novel, Ensembl rs1947429048, REVEL 0.26, CADD 17.80, Variant assessed as somatic; moderate impact.
- A9D (p.Ala9Asp), gnomAD 12-49962043-C-A, REVEL 0.28, CADD 21.70
- A9V (p.Ala9Val), gnomAD 12-49962043-C-T, REVEL 0.28, CADD 18.10
- A9A (p.Ala9Ala), rs1366365224, gnomAD 12-49962044-C-T, CADD 9.63
- F10L (p.Phe10Leu), gnomAD rs1434712483, REVEL 0.49, CADD 22.40
- F10S (p.Phe10Ser), gnomAD 12-49962046-T-C, REVEL 0.82, CADD 24.00
- L11P (p.Leu11Pro), 1000Genomes rs575071552, ExAC rs575071552, TOPMed rs575071552, gnomAD rs575071552, REVEL 0.66, CADD 4.29
- L11F (p.Leu11Phe), gnomAD 12-49962048-C-T, REVEL 0.23, CADD 0.00
- L11I (p.Leu11Ile), gnomAD 12-49962048-C-A, REVEL 0.27, CADD 0.00
- L11L (p.Leu11Leu), rs1373414214, gnomAD 12-49962050-C-G, CADD 7.98
- K12R (p.Lys12Arg), ExAC rs746804140, TOPMed rs746804140, gnomAD rs746804140, REVEL 0.15, CADD 5.01
- A13V (p.Ala13Val), ExAC rs770591290, TOPMed rs770591290, gnomAD rs770591290, REVEL 0.72, CADD 24.60
- A13S (p.Ala13Ser), gnomAD 12-49962054-G-T, REVEL 0.64, CADD 22.90
- A13A (p.Ala13Ala), gnomAD 12-49962056-C-A, CADD 0.29
- V14L (p.Val14Leu), ExAC rs776651494, gnomAD rs776651494
- V14M (p.Val14Met), rs776651494, NCI-TCGA Cosmic COSV5222, ExAC rs776651494, gnomAD rs776651494, REVEL 0.47, CADD 23.60, Variant assessed as somatic; moderate impact.
- F15L (p.Phe15Leu), ExAC rs745767685, TOPMed rs745767685, gnomAD rs745767685, REVEL 0.29, CADD 0.63
- F15S (p.Phe15Ser), Ensembl rs1592820456
- A16E (p.Ala16Glu), ESP rs138665659, TOPMed rs138665659, gnomAD rs138665659
- A16S (p.Ala16Ser), ExAC rs532533853, TOPMed rs532533853, gnomAD rs532533853, REVEL 0.48, CADD 21.80
- A16T (p.Ala16Thr), rs532533853, NCI-TCGA Cosmic COSV5223, ExAC rs532533853, TOPMed rs532533853, REVEL 0.40, CADD 22.50, Variant assessed as somatic; moderate impact.
- A16V (p.Ala16Val), ESP rs138665659, TOPMed rs138665659, gnomAD rs138665659, REVEL 0.42, CADD 22.20
- A16A (p.Ala16Ala), gnomAD 12-49962065-A-G, CADD 0.51
- E17V (p.Glu17Val), gnomAD 12-49962064-CAG-C, CADD 26.50
- F18L (p.Phe18Leu), 1000Genomes rs540509756, ExAC rs540509756, gnomAD rs540509756, REVEL 0.56, CADD 19.80
- F18S (p.Phe18Ser), gnomAD rs1464257093, REVEL 0.79, CADD 25.90
- L19S (p.Leu19Ser), ExAC rs762076378, gnomAD rs762076378, REVEL 0.70, CADD 25.40
- L19W (p.Leu19Trp), ExAC rs762076378, gnomAD rs762076378, REVEL 0.70, CADD 25.70
- L19L (p.Leu19Leu), gnomAD 12-49962074-G-A, CADD 7.84
- A20T (p.Ala20Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A20S (p.Ala20Ser), gnomAD 12-49962073-TGGCC, CADD 27.40
- A20V (p.Ala20Val), gnomAD 12-49962076-C-T, REVEL 0.75, CADD 23.80
- A20A (p.Ala20Ala), gnomAD 12-49962077-C-A, CADD 10.50
- T21S (p.Thr21Ser), gnomAD 12-49962075-GCCAC, CADD 25.20
- T21N (p.Thr21Asn), gnomAD 12-49962079-C-A, REVEL 0.89, CADD 23.30
- T21T (p.Thr21Thr), rs1947429813, gnomAD 12-49962080-C-T, CADD 3.41
- L22F (p.Leu22Phe), gnomAD rs568521335, REVEL 0.24, CADD 11.00, Uncertain significance, not specified
- L22P (p.Leu22Pro), gnomAD 12-49962082-T-C, REVEL 0.83, CADD 19.10
- L22L (p.Leu22Leu), rs773360590, gnomAD 12-49962083-C-T, CADD 8.23
- I23A (p.Ile23Ala), gnomAD 12-49962082-TCATC, CADD 27.20
- I23T (p.Ile23Thr), gnomAD 12-49962085-T-C, REVEL 0.72, CADD 26.00
- I23I (p.Ile23Ile), rs761134661, gnomAD 12-49962086-C-T, CADD 12.00
- F24S (p.Phe24Ser), 1000Genomes rs142676062, ESP rs142676062, ExAC rs142676062, TOPMed rs142676062, REVEL 0.79, CADD 25.30
- F24F (p.Phe24Phe), rs1381695244, gnomAD 12-49962089-C-T, CADD 8.74
- F24L (p.Phe24Leu), gnomAD 12-49962089-C-A, REVEL 0.51, CADD 18.60
- V25I (p.Val25Ile), rs1947430075, ClinGen CA384769146, ClinVar RCV004420047, TOPMed rs1947430075, REVEL 0.28, CADD 20.30, Uncertain significance, not specified
- V25L (p.Val25Leu), TOPMed rs1947430075, gnomAD rs1947430075, Uncertain significance
- F26V (p.Phe26Val), Ensembl rs2137157050
- F26L (p.Phe26Leu), gnomAD 12-49962095-C-A, REVEL 0.58, CADD 20.40
- G28G (p.Gly28Gly), gnomAD 12-49962101-C-T, CADD 8.35
- L29Q (p.Leu29Gln), gnomAD 12-49962103-T-A, REVEL 0.57, CADD 26.30
- L29L (p.Leu29Leu), rs1161972309, gnomAD 12-49962104-G-C, CADD 0.52
- G30C (p.Gly30Cys), TOPMed rs139623970, gnomAD rs139623970, REVEL 0.74, CADD 26.20, Uncertain significance
- G30D (p.Gly30Asp), rs754419280, NCI-TCGA Cosmic COSV9952, ExAC rs754419280, gnomAD rs754419280, REVEL 0.77, CADD 23.70, Variant assessed as somatic; moderate impact.
- G30R (p.Gly30Arg), TOPMed rs139623970, gnomAD rs139623970, Uncertain significance
- G30S (p.Gly30Ser), rs139623970, ClinGen CA236692301, NCI-TCGA Cosmic COSV9952, ClinVar RCV001355639, REVEL 0.78, CADD 25.50, Uncertain significance, not specified
- G30V (p.Gly30Val), gnomAD 12-49962106-G-T, REVEL 0.75, CADD 23.60
- G30G (p.Gly30Gly), rs759929671, gnomAD 12-49962107-C-T, CADD 8.46
- S31W (p.Ser31Trp), NCI-TCGA Cosmic COSV5223, Variant assessed as somatic; moderate impact.
- S31L (p.Ser31Leu), gnomAD 12-49962109-C-T, REVEL 0.75, CADD 24.50
- S31* (p.Ser31Ter), gnomAD 12-49962109-C-A, CADD 35.00
- S31S (p.Ser31Ser), gnomAD 12-49962110-G-C, CADD 1.27
- A32T (p.Ala32Thr), gnomAD 12-49962111-G-A, REVEL 0.53, CADD 23.00
- A32A (p.Ala32Ala), gnomAD 12-49962113-C-G, CADD 5.79
- L33P (p.Leu33Pro), gnomAD 12-49962115-T-C, REVEL 0.89, CADD 25.80
- K34R (p.Lys34Arg), TOPMed rs1351853699, gnomAD rs1351853699, REVEL 0.08, CADD 7.92
- K34T (p.Lys34Thr), TOPMed rs1351853699, gnomAD rs1351853699
- K34K (p.Lys34Lys), rs764870560, gnomAD 12-49962119-G-A, CADD 3.66
- W35* (p.Trp35Ter), ExAC rs752243612, gnomAD rs752243612, CADD 35.00
- W35R (p.Trp35Arg), Ensembl rs1947430513
- P36L (p.Pro36Leu), ExAC rs757913702, TOPMed rs757913702, gnomAD rs757913702, REVEL 0.56, CADD 22.40
- P36Q (p.Pro36Gln), ExAC rs757913702, TOPMed rs757913702, gnomAD rs757913702, REVEL 0.53, CADD 21.80
- P36S (p.Pro36Ser), Ensembl rs146740002
- P36P (p.Pro36Pro), rs777598357, gnomAD 12-49962125-G-T, CADD 0.59
- S37L (p.Ser37Leu), rs1328341018, NCI-TCGA Cosmic COSV5223, gnomAD rs1328341018, REVEL 0.27, CADD 5.69, Variant assessed as somatic; moderate impact.
- S37del (p.Ser37del), rs1365565400, gnomAD 12-49962123-CCGT-, CADD 14.60
- S37S (p.Ser37Ser), rs973567433, gnomAD 12-49962128-G-A, CADD 4.84
- A38E (p.Ala38Glu), rs398123054, ClinGen CA144807, ClinVar RCV000055668, ClinVar RCV003556140, REVEL 0.42, CADD 15.50, Pathogenic, not provided
- A38V (p.Ala38Val), ExAC rs398123054, TOPMed rs398123054, gnomAD rs398123054, REVEL 0.30, CADD 18.90, Pathogenic
- A38A (p.Ala38Ala), gnomAD 12-49962131-G-T, CADD 1.99
- L39L (p.Leu39Leu), gnomAD 12-49962132-C-T, CADD 6.03
- P40P (p.Pro40Pro), gnomAD 12-49962137-T-C, CADD 8.87
- T41A (p.Thr41Ala), gnomAD rs1947431229, REVEL 0.28, CADD 0.09
- T41T (p.Thr41Thr), rs780815226, gnomAD 12-49962140-C-G, CADD 4.25
- I42V (p.Ile42Val), TOPMed rs1244523495, gnomAD rs1244523495, REVEL 0.13, CADD 0.09
- I42I (p.Ile42Ile), gnomAD 12-49962143-C-A, CADD 0.59
- L43P (p.Leu43Pro), ExAC rs745880687, TOPMed rs745880687, REVEL 0.81, CADD 24.60
- L43H (p.Leu43His), gnomAD 12-49962138-A-ACC, CADD 18.50
- Q44L (p.Gln44Leu), TOPMed rs1947431383, REVEL 0.68, CADD 24.30
- I45S (p.Ile45Ser), rs398123055, ClinGen CA144809, ClinVar RCV000055670, UniProt VAR 070443, AlphaMissense 0.88, MetaLR 0.73, Pathogenic, Palmoplantar keratoderma, Bothnian type
- I45I (p.Ile45Ile), rs1474985654, gnomAD 12-49962152-C-T, CADD 6.73
- A46P (p.Ala46Pro), TOPMed rs1481308684, gnomAD rs1481308684, REVEL 0.54, CADD 8.17
- A46T (p.Ala46Thr), TOPMed rs1481308684, gnomAD rs1481308684, REVEL 0.48, CADD 7.10
- A46V (p.Ala46Val), ESP rs199524477, ExAC rs199524477, TOPMed rs199524477, gnomAD rs199524477, REVEL 0.43, CADD 23.80, Uncertain significance, not specified
- L47V (p.Leu47Val), TOPMed rs1947431690
- A48T (p.Ala48Thr), ExAC rs779906043, gnomAD rs779906043, REVEL 0.20, CADD 16.50
- A48V (p.Ala48Val), gnomAD 12-49962160-C-T, REVEL 0.57, CADD 23.90
- G50D (p.Gly50Asp), NCI-TCGA TCGA novel, REVEL 0.77, CADD 23.70, Variant assessed as somatic; moderate impact.
- G50V (p.Gly50Val), gnomAD 12-49962166-G-T, REVEL 0.71, CADD 23.70
- L51V (p.Leu51Val), TOPMed rs1157410332, gnomAD rs1157410332, REVEL 0.54, CADD 18.20
- L51L (p.Leu51Leu), gnomAD 12-49962168-C-T, CADD 5.44
- L51M (p.Leu51Met), gnomAD 12-49962168-C-A, REVEL 0.51, CADD 19.10
- A52D (p.Ala52Asp), TOPMed rs1446033559, REVEL 0.76, CADD 23.30, Uncertain significance, not specified
- A52T (p.Ala52Thr), Ensembl rs139174720
- A52V (p.Ala52Val), gnomAD 12-49962172-C-T, REVEL 0.39, CADD 17.20
- I53M (p.Ile53Met), ExAC rs748233977, TOPMed rs748233977, gnomAD rs748233977, REVEL 0.44, CADD 4.13
- I53T (p.Ile53Thr), gnomAD rs1406235581, REVEL 0.51, CADD 19.10
- I53V (p.Ile53Val), TOPMed rs1416410538, gnomAD rs1416410538, REVEL 0.29, CADD 15.50
- I53I (p.Ile53Ile), rs748233977, gnomAD 12-49962176-A-T, CADD 0.48
- G54D (p.Gly54Asp), NCI-TCGA TCGA novel, REVEL 0.55, CADD 22.30, Variant assessed as somatic; moderate impact.
- G54R (p.Gly54Arg), gnomAD 12-49962175-T-TA, CADD 22.40
- G54V (p.Gly54Val), gnomAD 12-49962178-G-T, REVEL 0.52, CADD 22.20
- G54G (p.Gly54Gly), gnomAD 12-49962179-C-G, CADD 7.60
- T55M (p.Thr55Met), TOPMed rs1348251687, gnomAD rs1348251687, REVEL 0.55, CADD 22.00
- T55R (p.Thr55Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T55T (p.Thr55Thr), rs772102909, gnomAD 12-49962182-G-A, CADD 0.90
- L56M (p.Leu56Met), TOPMed rs1947432029
- L56Q (p.Leu56Gln), Ensembl rs1947432060
- L56L (p.Leu56Leu), gnomAD 12-49962183-C-T, CADD 2.72
- A57T (p.Ala57Thr), gnomAD 12-49962186-G-A, REVEL 0.34, CADD 24.10
- A57V (p.Ala57Val), gnomAD 12-49962187-C-T, REVEL 0.15, CADD 0.10
- A57A (p.Ala57Ala), rs773450425, gnomAD 12-49962188-C-A, CADD 1.36
- Q58* (p.Gln58Ter), rs1349801845, NCI-TCGA Cosmic COSV9952, gnomAD rs1349801845, CADD 35.00, Variant assessed as somatic; high impact.
- Q58H (p.Gln58His), gnomAD 12-49962191-G-C, REVEL 0.78, CADD 21.70
- Q58Q (p.Gln58Gln), gnomAD 12-49962191-G-A, CADD 5.39
- A59G (p.Ala59Gly), gnomAD rs1226491229
- A59V (p.Ala59Val), gnomAD rs1226491229, REVEL 0.26, CADD 13.70
- A59D (p.Ala59Asp), gnomAD 12-49962193-C-A, REVEL 0.70, CADD 22.60
- L60V (p.Leu60Val), gnomAD rs1285794353, REVEL 0.21, CADD 2.79
- L60L (p.Leu60Leu), rs1187289790, gnomAD 12-49962197-G-A, CADD 6.89
- G61E (p.Gly61Glu), NCI-TCGA TCGA novel, REVEL 0.88, CADD 25.40, Variant assessed as somatic; moderate impact.
- G61* (p.Gly61Ter), gnomAD 12-49962198-G-T, CADD 35.00
- G61V (p.Gly61Val), gnomAD 12-49962199-G-T, REVEL 0.87, CADD 25.30
- G61G (p.Gly61Gly), gnomAD 12-49962200-A-C, CADD 4.09
- P62A (p.Pro62Ala), ExAC rs771368210, gnomAD rs771368210, REVEL 0.34, CADD 16.40
- P62T (p.Pro62Thr), ExAC rs771368210, gnomAD rs771368210, REVEL 0.36, CADD 17.60
- P62L (p.Pro62Leu), gnomAD 12-49962202-C-T, REVEL 0.42, CADD 15.30
- V63L (p.Val63Leu), TOPMed rs993506836, gnomAD rs993506836
- V63M (p.Val63Met), TOPMed rs993506836, gnomAD rs993506836, REVEL 0.53, CADD 23.40
- V63* (p.Val63Ter), gnomAD 12-49962200-AC-A, CADD 22.70
- V63V (p.Val63Val), gnomAD 12-49962206-G-C, CADD 4.99
- S64N (p.Ser64Asn), gnomAD 12-49962208-G-A, REVEL 0.84, CADD 24.70
- S64I (p.Ser64Ile), gnomAD 12-49962208-G-T, REVEL 0.91, CADD 25.40
- S64S (p.Ser64Ser), rs765854166, gnomAD 12-49962209-C-T, CADD 6.10
- G65C (p.Gly65Cys), ESP rs147337355, ExAC rs147337355, TOPMed rs147337355, gnomAD rs147337355, REVEL 0.90, CADD 26.50, Likely benign
- G65S (p.Gly65Ser), rs147337355, ClinGen CA6559432, ClinVar RCV003561435, ClinVar RCV006382033, REVEL 0.91, CADD 25.80, Conflicting interpretations, not provided; not specified
- G65G (p.Gly65Gly), rs763675133, gnomAD 12-49962212-C-T, CADD 0.17
- G66S (p.Gly66Ser), gnomAD rs1483056077, REVEL 0.64, CADD 25.60
- G66C (p.Gly66Cys), gnomAD 12-49962213-G-T, REVEL 0.67, CADD 25.60
- G66V (p.Gly66Val), gnomAD 12-49962214-G-T, REVEL 0.73, CADD 20.70
- I68S (p.Ile68Ser), ExAC rs751297059, gnomAD rs751297059, REVEL 0.86, CADD 25.10
- I68V (p.Ile68Val), TOPMed rs1947432734, REVEL 0.16, CADD 15.40
- I68I (p.Ile68Ile), gnomAD 12-49962221-C-T, CADD 9.23
- N69T (p.Asn69Thr), gnomAD rs1473313840, REVEL 0.90, CADD 24.50
- N69N (p.Asn69Asn), gnomAD 12-49962224-C-T, CADD 7.80
- P70H (p.Pro70His), Ensembl rs144062328
- P70S (p.Pro70Ser), gnomAD 12-49962225-C-T, REVEL 0.92, CADD 24.50
- P70P (p.Pro70Pro), rs1162999373, gnomAD 12-49962227-C-T, CADD 0.32
Public AQP5 analysis runs
- AQP5 analysis run — AQP5 (636 variants) — completed 2026-08-20