ABHD12

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

Basic information

Region (hg38): 20:25294742-25390835

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
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 (436 variants)
Inborn_genetic_diseases (59 variants)
PHARC_syndrome (49 variants)
ABHD12-related_disorder (18 variants)
Retinal_dystrophy (13 variants)
not_specified (12 variants)
Cone_dystrophy (2 variants)
Syndromic_retinitis_pigmentosa (1 variants)
Optic_atrophy (1 variants)
Hearing_impairment (1 variants)
See_cases (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. These statistics are base on transcript: NM_001042472.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		5 clinvar	88 clinvar	1 clinvar	95
missense	3 clinvar	3 clinvar	196 clinvar	9 clinvar	1 clinvar	212
nonsense	14 clinvar	3 clinvar	1 clinvar	1 clinvar		19
start loss						0
frameshift	15 clinvar	4 clinvar	3 clinvar			22
splice donor/acceptor (+/-2bp)	1 clinvar	6 clinvar	1 clinvar			8
Total	34	16	206	98	2

Highest pathogenic variant AF is 0.0000676319

Loading clinvar variants...

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