ABHD5

abhydrolase domain containing 5, lysophosphatidic acid acyltransferase, the group of Abhydrolase domain containing

Basic information

Region (hg38): 3:43690108-43734371

Links

ENSG00000011198

∙ NCBI:51099 ∙ OMIM:604780 ∙ HGNC:21396 ∙ Uniprot:Q8WTS1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Dorfman-Chanarin disease (Definitive), mode of inheritance: AR
Dorfman-Chanarin disease (Strong), mode of inheritance: AR
Dorfman-Chanarin disease (Strong), mode of inheritance: AR
Dorfman-Chanarin disease (Supportive), mode of inheritance: AR
Dorfman-Chanarin disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chanarin-Dorfman syndrome	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	Biochemical; Dermatologic	10712205; 11590543; 21757733; 22245374; 22373837; 25468645
Manifestations can include severe hepatic sequelae

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABHD5 gene.

not_provided (182 variants)
Triglyceride_storage_disease_with_ichthyosis (48 variants)
Inborn_genetic_diseases (37 variants)
ABHD5-related_disorder (8 variants)
not_specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABHD5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016006.6. 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			3 clinvar	57 clinvar	2 clinvar	62
missense	3 clinvar	2 clinvar	89 clinvar	6 clinvar	1 clinvar	101
nonsense	8 clinvar	3 clinvar				11
start loss						0
frameshift	6 clinvar	2 clinvar				8
splice donor/acceptor (+/-2bp)	3 clinvar	2 clinvar				5
Total	20	9	92	63	3

Highest pathogenic variant AF is 0.0000123908

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABHD5	protein_coding	protein_coding	ENST00000458276	7	44259

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.42e-7	0.893	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.474	166	184	0.902	0.00000933	2261
Missense in Polyphen		32	47.916	0.66784		614
Synonymous	-1.98	86	65.6	1.31	0.00000343	679
Loss of Function	1.63	13	21.1	0.618	0.00000150	218

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000242
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.0000880	0.0000879
Middle Eastern	0.000272	0.000272
South Asian	0.000327	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Lysophosphatidic acid acyltransferase which functions in phosphatidic acid biosynthesis (PubMed:18606822). May regulate the cellular storage of triacylglycerol through activation of the phospholipase PNPLA2 (PubMed:16679289). Involved in keratinocyte differentiation (PubMed:18832586). Regulates lipid droplet fusion (By similarity). {ECO:0000250|UniProtKB:Q9DBL9, ECO:0000269|PubMed:16679289, ECO:0000269|PubMed:18606822, ECO:0000269|PubMed:18832586}.;
Disease: DISEASE: Chanarin-Dorfman syndrome (CDS) [MIM:275630]: An autosomal recessive inborn error of lipid metabolism with multisystemic accumulation of triglycerides although plasma concentrations are normal. Clinical characteristics are congenital generalized ichthyosis, vacuolated leukocytes, hepatomegaly, myopathy, cataracts, neurosensory hearing loss and developmental delay. The disorder presents at birth with generalized, fine, white scaling of the skin and a variable degree of erythema resembling non-bullous congenital ichthyosiform erythroderma. {ECO:0000269|PubMed:11590543, ECO:0000269|PubMed:16679289, ECO:0000269|PubMed:17495960, ECO:0000269|PubMed:18606822}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Regulation of lipolysis in adipocytes - Homo sapiens (human);Lipid Metabolism Pathway;Liver steatosis AOP;Metabolism of lipids;Metabolism;CDP-diacylglycerol biosynthesis;Triglyceride catabolism;Triglyceride metabolism;triacylglycerol biosynthesis (Consensus)

Recessive Scores

pRec: 0.163

Intolerance Scores

loftool: 0.469
rvis_EVS: -0.42
rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

pHI: 0.100
hipred: N
hipred_score: 0.333
ghis: 0.552

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.283

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Abhd5
Phenotype: immune system phenotype; skeleton phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype;

Gene ontology

Biological process: fatty acid metabolic process;phosphatidic acid biosynthetic process;negative regulation of sequestering of triglyceride;positive regulation of triglyceride catabolic process;cell differentiation;positive regulation of lipoprotein lipase activity;lipid homeostasis
Cellular component: lipid droplet;cytosol
Molecular function: 1-acylglycerol-3-phosphate O-acyltransferase activity;triglyceride lipase activity;lysophosphatidic acid acyltransferase activity;carboxylic ester hydrolase activity