ABHD12

abhydrolase domain containing 12, lysophospholipase, the group of Abhydrolase domain containing

Basic information

Region (hg38): 20:25294741-25390835

Previous symbols: [ "C20orf22" ]

Links

ENSG00000100997 ∙ NCBI:26090 ∙ OMIM:613599 ∙ HGNC:15868 ∙ Uniprot:Q8N2K0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• PHARC syndrome (Strong), mode of inheritance: AR
• PHARC syndrome (Supportive), mode of inheritance: AR
• PHARC syndrome (Strong), mode of inheritance: AR
• PHARC syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract	AR	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	Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic	19005174; 20797687; 22938382; 24697911

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABHD12 gene.

• not provided (434 variants)
• PHARC syndrome (69 variants)
• Inborn genetic diseases (26 variants)
• not specified (6 variants)
• Retinal dystrophy (6 variants)
• ABHD12-related condition (1 variants)
• Hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABHD12 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	57	5	64
missense		1	166	1	2	170
nonsense	7	3	2			12
start loss						0
frameshift	9	3	2			14
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	1	3				4
splice region			18	20	1	39
non coding			22	72	45	139
Total	17	11	195	130	52

Highest pathogenic variant AF is 0.0000263

Variants in ABHD12

This is a list of pathogenic ClinVar variants found in the ABHD12 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-25294917-GTTAGTT-G			Benign (Jun 24, 2018)
20-25294968-T-C		ABHD12-related disorder	Likely benign (Jun 17, 2020)
20-25294981-G-A			Benign (Jun 29, 2018)
20-25294985-T-C		not specified	Benign (Jun 24, 2018)
20-25294992-A-G			Uncertain significance (Feb 01, 2023)
20-25295038-A-G		ABHD12-related disorder	Likely benign (May 14, 2019)
20-25295121-AT-A			Likely benign (Jul 28, 2018)
20-25295159-C-G			Benign (Jan 25, 2019)
20-25295207-C-T			Benign (Nov 10, 2018)
20-25295234-A-G			Benign (Nov 10, 2018)
20-25295254-C-A			Benign (Nov 10, 2018)
20-25295615-T-C		not specified	Uncertain significance (Sep 23, 2023)
20-25295636-T-G		not specified	Uncertain significance (Nov 23, 2022)
20-25295666-A-G		not specified	Uncertain significance (Dec 11, 2023)
20-25296391-A-G		not specified	Uncertain significance (Jan 26, 2022)
20-25296415-T-C		not specified	Uncertain significance (Sep 12, 2023)
20-25296428-C-T		not specified	Uncertain significance (Dec 27, 2022)
20-25296437-G-A		not specified	Uncertain significance (Aug 16, 2021)
20-25296475-G-A		not specified	Uncertain significance (Mar 04, 2024)
20-25296503-C-G		not specified	Uncertain significance (Dec 17, 2023)
20-25296515-G-A		not specified	Uncertain significance (Oct 12, 2022)
20-25296517-G-T		not specified	Uncertain significance (Sep 17, 2021)
20-25300196-G-A		PHARC syndrome	Uncertain significance (Jun 14, 2016)
20-25300304-C-T		PHARC syndrome	Benign (Apr 27, 2017)
20-25300391-C-T		PHARC syndrome	Likely benign (Apr 27, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABHD12	protein_coding	protein_coding	ENST00000376542	13	96241

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000195	0.995	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.195	210	218	0.963	0.0000130	2590
Missense in Polyphen		59	74.593	0.79096		876
Synonymous	-0.0665	86	85.2	1.01	0.00000556	784
Loss of Function	2.47	12	25.5	0.471	0.00000148	269

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000293	0.000293
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.00	0.00
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Lysophosphatidylserine (LPS) lipase that plays a key role in the central nervous system. Represents a major LPS lipase in the brain (By similarity). May also have a 2- arachidonoylglycerol (2-AG) hydrolase activity and act as a regulator of endocannabinoid signaling pathways. {ECO:0000250|UniProtKB:Q99LR1, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24027063}.
• Disease: DISEASE: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) [MIM:612674]: A slowly progressive neurologic disorder with a variable phenotype resembling Refsum disease. Clinical features include sensorineural hearing loss, visual problems related to cataracts, retinitis pigmentosa, pes cavus, ataxic and/or spastic gait disturbances with a progressive sensorimotor peripheral neuropathy. Other features include hyporeflexia, hyperreflexia, extensor plantar responses. {ECO:0000269|PubMed:20797687, ECO:0000269|PubMed:22938382, ECO:0000269|PubMed:24027063}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signaling by GPCR;Signal Transduction;Effects of PIP2 hydrolysis;Platelet activation, signaling and aggregation;Arachidonate production from DAG;Hemostasis;triacylglycerol degradation;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Intolerance Scores

• loftool: 0.887
• rvis_EVS: -0.16
• rvis_percentile_EVS: 42.06

Haploinsufficiency Scores

• pHI: 0.0696
• hipred: N
• hipred_score: 0.269
• ghis: 0.543

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.232

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Abhd12
• Phenotype: hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; muscle phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: abhd12
• Affected structure: eye photoreceptor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein depalmitoylation;phosphatidylserine catabolic process;adult walking behavior;response to auditory stimulus;acylglycerol catabolic process;glycerophospholipid catabolic process;monoacylglycerol catabolic process
• Cellular component: plasma membrane;integral component of membrane;AMPA glutamate receptor complex;dendrite cytoplasm
• Molecular function: lysophospholipase activity;palmitoyl-(protein) hydrolase activity;acylglycerol lipase activity