AQP5

aquaporin 5, the group of Aquaporins

Basic information

Region (hg38): 12:49961872-49965682

Links

ENSG00000161798 ∙ NCBI:362 ∙ OMIM:600442 ∙ HGNC:638 ∙ Uniprot:P55064 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• palmoplantar keratoderma, Bothnian type (Strong), mode of inheritance: AD
• palmoplantar keratoderma, Bothnian type (Strong), mode of inheritance: AD
• nonepidermolytic palmoplantar keratoderma (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Palmoplantar keratoderma, Bothnian type	AD	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	Dermatologic	23830519

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AQP5 gene.

• Palmoplantar keratoderma, Bothnian type (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AQP5 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				2	4	6
missense	1	1	21	6	3	32
nonsense						0
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1	13	14
Total	1	1	21	10	20

Highest pathogenic variant AF is 0.00000657

Variants in AQP5

This is a list of pathogenic ClinVar variants found in the AQP5 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-49962019-TGAA-T		AQP5-related disorder	Likely benign (Jun 01, 2024)
12-49962050-C-A			Likely benign (Aug 15, 2023)
12-49962090-G-A		not specified	Uncertain significance (Dec 15, 2023)
12-49962105-G-A			Uncertain significance (-)
12-49962130-C-A		Palmoplantar keratoderma, Bothnian type	Pathogenic (Jan 22, 2023)
12-49962151-T-G		Palmoplantar keratoderma, Bothnian type	Pathogenic (Aug 08, 2013)
12-49962210-G-A			Likely benign (Nov 15, 2023)
12-49962273-C-T		not specified	Uncertain significance (Aug 02, 2021)
12-49962274-G-A		not specified	Uncertain significance (Nov 30, 2022)
12-49962346-C-T			Uncertain significance (Feb 01, 2024)
12-49962352-A-G			Uncertain significance (Sep 01, 2023)
12-49962372-G-A		not specified	Likely benign (Jun 29, 2023)
12-49962386-T-G			Benign (Mar 17, 2023)
12-49962391-TG-T			Benign (Jan 29, 2024)
12-49962391-TGGG-T			Benign (Jan 29, 2024)
12-49962391-TGGGG-T			Benign (Jan 22, 2024)
12-49962391-T-TG			Benign (Aug 31, 2023)
12-49962391-T-TGG			Benign (Nov 03, 2023)
12-49962394-G-A			Benign (Dec 11, 2023)
12-49963477-G-C			Benign (Aug 04, 2023)
12-49963495-A-G		Palmoplantar keratoderma, Bothnian type	Pathogenic (Aug 08, 2013)
12-49963497-C-A			Uncertain significance (Sep 05, 2023)
12-49963508-C-T			Uncertain significance (Aug 17, 2023)
12-49963509-G-A			Likely benign (Nov 17, 2022)
12-49963588-C-T		AQP5-related disorder	Likely benign (Jun 05, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AQP5	protein_coding	protein_coding	ENST00000293599	4	3812

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0532	0.871	125727	0	16	125743	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.376	156	170	0.919	0.0000105	1671
Missense in Polyphen		57	65.879	0.86522		633
Synonymous	0.261	80	83.0	0.964	0.00000570	607
Loss of Function	1.48	3	7.31	0.411	3.11e-7	80

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000249	0.000240
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000708	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000658	0.0000653
Other	0.00	0.00

dbNSFP

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.
• Pathway: 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 (Consensus)

Recessive Scores

• pRec: 0.241

Intolerance Scores

• loftool: 0.199
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.37

Haploinsufficiency Scores

• pHI: 0.379
• hipred: N
• hipred_score: 0.252
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.786

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aqp5
• Phenotype: digestive/alimentary phenotype; respiratory system 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); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: water transport;excretion;carbon dioxide transport;pancreatic juice secretion;odontogenesis;saliva secretion;camera-type eye morphogenesis;transmembrane transport
• Cellular component: endoplasmic reticulum;plasma membrane;integral component of plasma membrane;microvillus;basal plasma membrane;integral component of membrane;apical plasma membrane;extracellular exosome
• Molecular function: protein binding;water channel activity;identical protein binding