ABHD2

Chr 15

abhydrolase domain containing 2, acylglycerol lipase

Also known as: HS1-2, LABH2, PHPS1-2

NCBI Gene: 11057 ENSG00000140526 UniProt: P08910 OMIM: 612196

The protein is a progesterone-dependent acylglycerol lipase that hydrolyzes endocannabinoid arachidonoylglycerol from cell membranes and plays a key role in sperm capacitation by degrading inhibitors of the sperm calcium channel CatSper. The gene is highly constrained against loss-of-function variants (LOEUF 0.431), but no established Mendelian diseases have been reported in association with ABHD2 mutations to date. Any potential disorders would likely follow autosomal inheritance patterns.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein containing an alpha/beta hydrolase fold, which is a catalytic domain found in a wide range of enzymes. The encoded protein is an acylglycerol lipase that catalyzes the hydrolysis of endocannabinoid arachidonoylglycerol from the cell membrane. This leads to activation of the sperm calcium channel CatSper, which results in sperm activation. Alternative splicing of this gene results in two transcript variants encoding the same protein. [provided by RefSeq, Jan 2017]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in ABHD2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

431 rare PASS variants

Rare truncating (LoF)

1 in 7,800

41 rare PASS variants

Rare synonymous (reference)

1 in 110

222 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ABHD2. 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 390	1 in 8,400
South Asian	~43k	1 in 270	1 in 6,200
Remaining (unassigned)	~30k	1 in 150	≈ 1 in 30,000
European (Finnish)	~27k	1 in 830	none seen
Admixed American	~22k	1 in 190	≈ 1 in 4,500
African / African American	~21k	1 in 190	≈ 1 in 6,000
East Asian	~20k	1 in 260	none seen
Ashkenazi Jewish	~13k	1 in 650	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 260	≈ 1 in 2,900

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 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓