AQP5

Chr 12AD

aquaporin 5

Also known as: AQP-5, PPKB

NCBI Gene: 362 ENSG00000161798 UniProt: P55064 OMIM: 600442

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Palmoplantar keratoderma, Bothnian typeMIM #600231

UniProtKeratoderma, palmoplantar, Bothnian type

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Palmoplantar keratoderma, Bothnian type; no ClinGen or GenCC tier

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

160

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.06

LOEUF

GOF*

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.06LOEUF

pLI 0.053

Z-score 1.48

OE 0.41 (0.19–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.38Z-score

OE missense 0.92 (0.81–1.05)

156 obs / 169.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.19–1.06)

0≤0.351.4

Missense OE?0.92 (0.81–1.05)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 3 / 7.3Missense obs/exp: 156 / 169.8Syn Z: 0.26

Background carrier burden — how many people carry a rare variant somewhere in AQP5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

377 rare PASS variants

Rare truncating (LoF)

1 in 640

40 rare PASS variants

Rare synonymous (reference)

1 in 300

189 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AQP5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 630
South Asian	~43k	1 in 130	1 in 7,400
Remaining (unassigned)	~30k	1 in 130	1 in 680
European (Finnish)	~27k	1 in 270	none seen
Admixed American	~22k	1 in 100	1 in 3,800
African / African American	~21k	1 in 190	1 in 2,000
East Asian	~20k	1 in 110	≈ 1 in 9,300
Ashkenazi Jewish	~13k	1 in 590	1 in 360
Middle Eastern	~2,884	1 in 130	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓