CES5A

Chr 16

carboxylesterase 5A

Also known as: CAUXIN, CES4C1, CES5, CES7, HEL126

NCBI Gene: 221223 ENSG00000159398 UniProt: Q6NT32 OMIM: 618678

The CES5A protein is a secreted carboxylesterase that hydrolyzes xenobiotics, endogenous substrates with ester/thioester/amide bonds, and participates in fatty acid and cholesterol ester metabolism. This gene shows very low constraint against loss-of-function variants and currently has no established association with human disease. CES5A is predominantly expressed in brain, kidney, lung, and testis, and may contribute to blood-brain barrier function and lipid transfer processes.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They also participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This gene, also called CES5, is predominantly expressed in peripheral tissues, including brain, kidney, lung and testis. It encodes a secreted enzyme. Because of high levels in the urine of male domestic cats, this enzyme is also called cauxin (carboxylesterase-like urinary excreted protein). The enzyme functions in regulating the production of a pheromone precursor and may contribute to lipid and cholesterol transfer processes within male reproductive fluids. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.58

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.58LOEUF

pLI 0.000

Z-score -1.10

OE 1.21 (0.94–1.58)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.11Z-score

OE missense 1.02 (0.93–1.11)

337 obs / 331.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.21 (0.94–1.58)

0≤0.351.4

Missense OE?1.02 (0.93–1.11)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 39 / 32.3Missense obs/exp: 337 / 331.3Syn Z: -0.41

Background carrier burden — how many people carry a rare variant somewhere in CES5A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 39

884 rare PASS variants

Rare truncating (LoF)

1 in 250

173 rare PASS variants

Rare synonymous (reference)

1 in 85

356 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CES5A. 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 54	1 in 280
South Asian	~43k	1 in 41	1 in 260
Remaining (unassigned)	~30k	1 in 46	1 in 270
European (Finnish)	~27k	1 in 170	1 in 2,200
Admixed American	~22k	1 in 41	1 in 150
African / African American	~21k	1 in 42	1 in 380
East Asian	~20k	1 in 63	1 in 230
Ashkenazi Jewish	~13k	1 in 120	1 in 1,500
Middle Eastern	~2,884	1 in 42	1 in 290

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 13 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 13.? see exons ↓