ABHD2
protein-codingabhydrolase domain containing 2, acylglycerol lipase, the group of Abhydrolase domain containing
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~114.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ABHD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152924.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 42 | 42 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 46 | 0 | 3 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_690888.1 | 9 | MANE Select | |
| Ensembl | ENSP00000268129.5 | 9 | MANE Select | |
| RefSeq | NP_001403341.1 | 9 | Standard | |
| RefSeq | NP_001403342.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glucocorticoid Receptor Pathway
- Nuclear Receptors Meta-Pathway
Biological Process
- acrosome reaction
- response to wounding
- negative regulation of cell migration
- response to progesterone
- steroid hormone mediated signaling pathway
Molecular Function
- steroid hormone receptor activity
- lipase activity
- short-chain carboxylesterase activity
- hormone binding
- acylglycerol lipase activity
Cellular Component
- acrosomal vesicle
- integral component of membrane
- sperm flagellum
- sperm plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000352732
- Coding exons
- 9
- Length
- 114902
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125745
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.23 | 161 | 262 | 0.613 | 0.0000156 | 2798 |
| Missense (PolyPhen) | 24 | 73.467 | 0.32668 | 770 | ||
| Synonymous | -0.526 | 112 | 105 | 1.07 | 0.00000669 | 812 |
| Loss of Function | 3.46 | 4 | 21.2 | 0.188 | 9.98e-7 | 248 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Progesterone-dependent acylglycerol lipase that catalyzes hydrolysis of endocannabinoid arachidonoylglycerol (AG) from cell membrane (PubMed:26989199). Acts as a progesterone receptor: progesterone-binding activates the acylglycerol lipase activity, mediating degradation of 1-arachidonoylglycerol (1AG) and 2-arachidonoylglycerol (2AG) to glycerol and arachidonic acid (AA) (PubMed:26989199). Plays a key role in sperm capacitation in response to progesterone by mediating degradation of 2AG, an inhibitor of the sperm calcium channel CatSper, leading to calcium influx via CatSper and sperm activation (PubMed:26989199). May also play a role in smooth muscle cells migration (By similarity). {ECO:0000250|UniProtKB:Q9QXM0, ECO:0000269|PubMed:26989199}.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.419
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.695
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |