ABHD5

Summary

ABHD5 (abhydrolase domain containing 5, lysophosphatidic acid acyltransferase, HGNC:21396) is a protein-coding gene on chromosome 3p21.33, encoding 1-acylglycerol-3-phosphate O-acyltransferase ABHD5 (Q8WTS1). Coenzyme A-dependent lysophosphatidic acid acyltransferase that catalyzes the transfer of an acyl group on a lysophosphatidic acid.

The protein encoded by this gene belongs to a large family of proteins defined by an alpha/beta hydrolase fold, and contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. It differs from other members of this subfamily in that its putative catalytic triad contains an asparagine instead of the serine residue. Mutations in this gene have been associated with Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation.

Source: NCBI Gene 51099 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Dorfman-Chanarin disease (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 360 total — 23 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21396
Approved symbol	ABHD5
Name	abhydrolase domain containing 5, lysophosphatidic acid acyltransferase
Location	3p21.33
Locus type	gene with protein product
Status	Approved
Aliases	CGI-58, NCIE2
Ensembl gene	ENSG00000011198
Ensembl biotype	protein_coding
OMIM	604780
Entrez	51099

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 11 protein_coding, 7 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000013894, ENST00000413300, ENST00000454293, ENST00000456453, ENST00000458276, ENST00000463153, ENST00000486764, ENST00000642351, ENST00000643140, ENST00000643477, ENST00000643500, ENST00000643520, ENST00000644371, ENST00000646378, ENST00000646799, ENST00000649763, ENST00000910934, ENST00000910935, ENST00000967519, ENST00000967520

RefSeq mRNA: 4 — MANE Select: NM_016006 NM_001355186, NM_001365649, NM_001365650, NM_016006

CCDS: CCDS2711, CCDS93252, CCDS93253

Canonical transcript exons

ENST00000644371 — 7 exons

Exon	Start	End
ENSE00000764970	43711709	43711863
ENSE00000764971	43714947	43715058
ENSE00000764972	43717671	43717857
ENSE00001824591	43690938	43691039
ENSE00003521589	43702215	43702587
ENSE00003527253	43699276	43699361
ENSE00003815155	43718443	43722725

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 94.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.2443 / max 1344.9644, expressed in 1811 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36310	23.4225	1801
36309	3.6204	1641
36311	1.1086	827
36308	0.0927	26

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	94.38	gold quality
lower esophagus mucosa	UBERON:0035834	93.98	gold quality
upper leg skin	UBERON:0004262	93.78	gold quality
blood	UBERON:0000178	93.72	gold quality
skin of abdomen	UBERON:0001416	93.32	gold quality
skin of leg	UBERON:0001511	92.24	gold quality
islet of Langerhans	UBERON:0000006	92.11	gold quality
zone of skin	UBERON:0000014	92.02	gold quality
omental fat pad	UBERON:0010414	91.93	gold quality
peritoneum	UBERON:0002358	91.88	gold quality
monocyte	CL:0000576	91.69	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.55	gold quality
mononuclear cell	CL:0000842	91.50	gold quality
esophagus mucosa	UBERON:0002469	91.33	gold quality
leukocyte	CL:0000738	91.31	gold quality
minor salivary gland	UBERON:0001830	91.17	gold quality
mouth mucosa	UBERON:0003729	90.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.00	gold quality
bone marrow	UBERON:0002371	89.84	gold quality
right lung	UBERON:0002167	89.72	gold quality
stromal cell of endometrium	CL:0002255	89.42	gold quality
mammalian vulva	UBERON:0000997	89.17	gold quality
saliva-secreting gland	UBERON:0001044	88.99	gold quality
epithelium of esophagus	UBERON:0001976	88.92	gold quality
decidua	UBERON:0002450	88.85	gold quality
adipose tissue	UBERON:0001013	88.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.76	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.66	gold quality
esophagus squamous epithelium	UBERON:0006920	88.63	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.49	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	1129.41
E-MTAB-9841	yes	954.54
E-MTAB-6678	no	4.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

214 targeting ABHD5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939

Literature-anchored findings (GeneRIF, showing 40)

• mutational analysis in Chanarin-Dorfman syndrome (PMID:11590543)
• ABDH5 gene mutation is found in patients diagnosed with Chanarin Dorfman syndrome. (PMID:15967942)
• CGI-58 interacts with adipose triglyceride lipase, stimulating its TG hydrolase activity up to 20-fold (PMID:16679289)
• CGI-58 facilitates lipolysis in cooperation with perilipin and other factors, including lipases (PMID:17308334)
• analysis of a novel S115G mutation of CGI-58 in a Turkish patient with Dorfman-Chanarin syndrome [case report] (PMID:17495960)
• Deficient in lipid storage diseases. (PMID:17631826)
• These data enriches the list of CGI-58 mutations associated with Chanarin-Dorfman syndrome and confirms the clinical and allelic heterogeneity of this disease, especially the inconsistent muscle involvement. (PMID:18339307)
• CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid (PMID:18606822)
• CGI-58 is expressed and packaged into lamellar granules (LG) during keratinization and likely plays crucial role(s) in keratinocyte differentiation and LG lipid metabolism, contributing to skin lipid barrier formation. (PMID:18832586)
• Chanarin-Dorfman syndrome: deficiency in CGI-58, a lipid droplet-bound coactivator of lipase. (Review) (PMID:19061969)
• review summarizes recent findings with the goal of relating structural variants of ATGL and CGI-58 to functional consequences in lipid metabolism [review] (PMID:19401457)
• analysis of novel mutations in the ABHD5 gene in Chanarin-Dorfman syndrome (CDS) patients (PMID:20307695)
• CGI-58 not only facilitates triglyceride lipolysis, but also provides fatty acid for esterification of ceremide leading to acylceremides (PMID:20520629)
• First report of large genomic deletions in the ABHD5 gene in Chanarin-Dorfman syndrome patients from Mediterranean countries. (PMID:21122093)
• the C terminus sequesters ABHD5 and thus inhibits basal ATGL activity (PMID:21757733)
• A report of two Chanarin-Dorfman syndrome sisters with severe steatohepatitis and decompensated cirrhosis due to steatohepatitis in whom the clinical presentation developed due to a new mutation in ABHD5 gene. (PMID:22245374)
• A novel nonsense mutation of ABHD5 is reported in a consanguineous Afgani family with 4 sibs with Dorfman Chanarin syndrome; the mutation leads to protein truncation by 14 AAs; findings include liver cirrhosis, corneal opacities,tessellated fundus (PMID:22373837)
• an important metabolic function of CGI-58 in skeletal muscle (PMID:22383684)
• ABHD5, PGRMC1 and SQS are novel markers for sebaceous carcinoma and can reliably distinguish sebaceous neoplasms from non-sebaceous tumors, specifically BCC with clear cell features. (PMID:23557589)
• Prebinding CGI-58 with PI(3)P or PI(5)P did not alter its coactivation of ATGL in vitro. In summary, purified recombinant CGI-58 that is functional as an ATGL coactivator lacks LPAAT activity. (PMID:24879803)
• PLIN5 was significantly colocated with ATGL, mitochondria and CGI-58, indicating a close association between the key lipolytic effectors in resting skeletal muscle. (PMID:25054327)
• Findings indicate a molecular mechanisms by which lysophosphatidic acid acyltransferase CGI-58 regulates lipid homeostasis. (PMID:25315780)
• -mediated phosphorylation of CGI-58 is required for dispersion of CGI-58 from perilipin 1A-coated lipid droplets (PMID:25421061)
• Abhd5 expression falls substantially and correlates negatively with malignant features in human colorectal cancer. (PMID:25482557)
• this study presents clinical and molecular data of four affected relatives with Chanarin-Dorfman syndrome homozygous for a N209X mutation in ABHD5, and provides a short review by comparing patients with N209X homozygous mutations to patients with other ABHD5 mutations. (PMID:25682902)
• Authors show that rat ATGL, coactivated by rat CGI-58, efficiently hydrolyzes triglycerides and retinyl ester. (PMID:26330055)
• simultaneous tryptophan alanine permutations in both arms abolish localization and activity of CGI-58 as opposed to tryptophan substitutions that occur in only one arm. (PMID:26350461)
• novel ABHD5 truncating variant in a twenty nine month old female child, who presented with icthyosiform erythroderma. (PMID:26353074)
• Case Report: novel ABHD5 mutation, c.838C > T (p.Arg280*), in trans with p.Arg234* in a Chinese patient with very mild Dorfman-Chanarin syndrome. (PMID:26547112)
• These results indicate that HCV taps into the lipid droplet triglyceride reservoir usurping ABHD5 lipase cofactor function (PMID:27124600)
• ABHD5 possesses a PNPLA2-independent function in regulating autophagy and tumorigenesis. (PMID:27559856)
• It is clear that CGI-58 can regulate TAG hydrolysis by activating the major TAG hydrolase adipose triglyceride lipase (ATGL), yet CGI-58 can also regulate lipid metabolism via mechanisms that do not involve ATGL. (PMID:28827091)
• our findings indicate that inhibition of both DGAT1 and ABHD5 using siRNA leads to reduction in prostate cancer cell growth. (PMID:28877685)
• The results here report on three patients with mutations in the ichthyosis-related gene, ABHD5 involved in lipid metabolism, presenting with erythrokeratoderma. (PMID:29023646)
• ABHD5 is a potential therapeutic target against metastatic castration-resistant prostate cancer. (PMID:29026202)
• novel homozygote deletion in exon 4 of ABHD5 causing Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive metabolic disorder. (PMID:29475365)
• ABHD5 mutation is associated with Chanarin Dorfman Syndrome. (PMID:29843625)
• Study results suggest that ABHD5 functions to retain triglyceride, the substrate of PNPLA1, in the endoplasmic reticulum, the site of acylceramide production, and to present TG to PNPLA1. These findings reveal the molecular mechanism by which ABHD5 mutations cause ichthyosis symptoms in Chanarin-Dorfman syndrome. (PMID:30527376)
• Study report that although ABHD5 plays a tumor suppressor role in colorectal cancer (CRC) development and progression, it unexpectedly blunts the sensitivity of CRC cells to fluorouracil via promoting RNASET2-mediated autophagic uracil yield. (PMID:30842415)
• Inherited non-alcoholic fatty liver disease and dyslipidemia due to monoallelic ABHD5 mutations. (PMID:30954460)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Abhd5	ENSMUSG00000032540
rattus_norvegicus	Abhd5	ENSRNOG00000000221
drosophila_melanogaster	puml	FBGN0033226
caenorhabditis_elegans	C31H5.1	WBGENE00007854
caenorhabditis_elegans		WBGENE00017335
caenorhabditis_elegans		WBGENE00018077
caenorhabditis_elegans		WBGENE00019525
caenorhabditis_elegans		WBGENE00022258
caenorhabditis_elegans		WBGENE00022259
caenorhabditis_elegans		WBGENE00022260

Paralogs (12): ABHD4 (ENSG00000100439), EPHX3 (ENSG00000105131), ABHD11 (ENSG00000106077), MEST (ENSG00000106484), ABHD14B (ENSG00000114779), EPHX2 (ENSG00000120915), ABHD8 (ENSG00000127220), BPHL (ENSG00000137274), ABHD6 (ENSG00000163686), EPHX4 (ENSG00000172031), SERHL2 (ENSG00000183569), ABHD14A (ENSG00000248487)

Protein

Protein identifiers

1-acylglycerol-3-phosphate O-acyltransferase ABHD5 — Q8WTS1 (reviewed: Q8WTS1)

Alternative names: Abhydrolase domain-containing protein 5, Lipid droplet-binding protein CGI-58

All UniProt accessions (12): Q8WTS1, A0A0S2Z5D6, A0A2R8Y7S6, A0A2R8YER6, A0A2R8YEZ7, A0A2R8YG22, A0A2R8YG27, A0A2U3TZT9, C9J1D1, C9JBM3, F8W7B5, H7BZY9

UniProt curated annotations — full annotation on UniProt →

Function. Coenzyme A-dependent lysophosphatidic acid acyltransferase that catalyzes the transfer of an acyl group on a lysophosphatidic acid. Functions preferentially with 1-oleoyl-lysophosphatidic acid followed by 1-palmitoyl-lysophosphatidic acid, 1-stearoyl-lysophosphatidic acid and 1-arachidonoyl-lysophosphatidic acid as lipid acceptor. Functions preferentially with arachidonoyl-CoA followed by oleoyl-CoA as acyl group donors. Functions in phosphatidic acid biosynthesis. May regulate the cellular storage of triacylglycerol through activation of the phospholipase PNPLA2. Involved in keratinocyte differentiation. Regulates lipid droplet fusion.

Subunit / interactions. Interacts with ADRP, PLIN and PNPLA2. Interacts with PLIN5; promotes interaction with PNPLA2.

Subcellular location. Cytoplasm. Lipid droplet. Cytosol.

Tissue specificity. Widely expressed in various tissues, including lymphocytes, liver, skeletal muscle and brain. Expressed by upper epidermal layers and dermal fibroblasts in skin, hepatocytes and neurons (at protein level).

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Acyltransferase activity is inhibited by detergents such as Triton X-100 and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Acyltransferase activity is inhibited by the presence of magnesium and calcium.

Domain organisation. The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.

Induction. Up-regulated upon keratinocyte differentiation (at protein level).

Similarity. Belongs to the peptidase S33 family. ABHD4/ABHD5 subfamily.

RefSeq proteins (4): NP_001342115, NP_001352578, NP_001352579, NP_057090* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF00561

Catalyzed reactions (Rhea), 9 shown:

• a 1-acyl-sn-glycero-3-phosphate + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphate + CoA (RHEA:19709)
• 1-hexadecanoyl-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA (RHEA:33187)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA (RHEA:37131)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + hexadecanoyl-CoA = 1-(9Z)-octadecenoyl-2-hexadecanoyl-sn-glycero-3-phosphate + CoA (RHEA:37143)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + octadecanoyl-CoA = 1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycero-3-phosphate + CoA (RHEA:37147)
• 1-octadecanoyl-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA (RHEA:37163)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA = 1-(9Z)-octadecenoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate + CoA (RHEA:37443)
• eicosanoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-eicosanoyl-sn-glycero-3-phosphate + CoA (RHEA:37451)
• 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phosphate + CoA (RHEA:37455)

UniProt features (13 total): sequence variant 6, modified residue 2, initiator methionine 1, chain 1, sequence conflict 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WTS1-F1	87.62	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 2, 122

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-163560	Triglyceride catabolism
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8979227	Triglyceride metabolism

MSigDB gene sets: 345 (showing top): REACTOME_TRIGLYCERIDE_CATABOLISM, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_HOMEOSTASIS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GTGCCTT_MIR506, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GERY_CEBP_TARGETS

GO Biological Process (10): fatty acid metabolic process (GO:0006631), phosphatidic acid biosynthetic process (GO:0006654), negative regulation of triglyceride storage (GO:0010891), positive regulation of triglyceride catabolic process (GO:0010898), cell differentiation (GO:0030154), lipid homeostasis (GO:0055088), proteolysis (GO:0006508), lipid metabolic process (GO:0006629), phospholipid biosynthetic process (GO:0008654), positive regulation of lipid catabolic process (GO:0050996)

GO Molecular Function (9): 1-acylglycerol-3-phosphate O-acyltransferase activity (GO:0003841), lysophosphatidic acid acyltransferase activity (GO:0042171), carboxylic ester hydrolase activity (GO:0052689), lipase activator activity (GO:0060229), protein binding (GO:0005515), peptidase activity (GO:0008233), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleoplasm (GO:0005654), lipid droplet (GO:0005811), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Triglyceride metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
catalytic activity	2
lipid metabolic process	1
monocarboxylic acid metabolic process	1
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
negative regulation of lipid storage	1
regulation of triglyceride storage	1
triglyceride storage	1
regulation of triglyceride catabolic process	1
triglyceride catabolic process	1
positive regulation of lipid catabolic process	1
positive regulation of triglyceride metabolic process	1
cellular developmental process	1
chemical homeostasis	1
protein metabolic process	1
primary metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
positive regulation of catabolic process	1
lipid catabolic process	1
positive regulation of lipid metabolic process	1
regulation of lipid catabolic process	1
acylglycerol O-acyltransferase activity	1
lysophosphatidic acid acyltransferase activity	1
lysophospholipid acyltransferase activity	1
hydrolase activity, acting on ester bonds	1
enzyme activator activity	1
lipase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
transferase activity	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1954 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABHD5	PNPLA2	Q96AD5	999
ABHD5	PLIN1	O60240	995
ABHD5	PLIN5	Q00G26	928
ABHD5	LIPE	Q05469	914
ABHD5	PLIN2	Q99541	878
ABHD5	ALOXE3	Q9BYJ1	866
ABHD5	PNPLA3	Q9NST1	860
ABHD5	ALOX12B	O75342	859
ABHD5	PNPLA1	Q8N8W4	836
ABHD5	PLIN3	O60664	775
ABHD5	NIPAL4	Q0D2K0	770
ABHD5	PNPLA4	P41247	761
ABHD5	PNPLA5	Q7Z6Z6	754
ABHD5	MGLL	Q99685	748
ABHD5	G0S2	P27469	736

IntAct

76 interactions, top by confidence:

A	B	Type	Score
CLCN4	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
PLIN5	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
PCNX2	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
CERCAM	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
ABHD5	MIEF1	psi-mi:“MI:0915”(physical association)	0.560
	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
DGAT2L6	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
PLIN3	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
ABHD5	RUSC1	psi-mi:“MI:0915”(physical association)	0.560
GET1	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
COQ8A	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
ABHD5	PLIN2	psi-mi:“MI:0915”(physical association)	0.560
ABHD5	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.560
TPD52L2	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
SLC44A3	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
ABHD5	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
GRIA4	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
ZCCHC12	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
GAD2	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
ABHD5	RNF24	psi-mi:“MI:0915”(physical association)	0.560
RBFA	ABHD5	psi-mi:“MI:0915”(physical association)	0.560
ABHD5	ZPR1	psi-mi:“MI:0914”(association)	0.530

BioGRID (54): PLIN1 (FRET), ABHD5 (FRET), PLIN1 (PCA), PNPLA2 (PCA), PLIN1 (FRET), SKAP2 (Affinity Capture-MS), TRIM59 (Affinity Capture-MS), SARAF (Affinity Capture-MS), TMEM38B (Affinity Capture-MS), NRAS (Affinity Capture-MS), ZPR1 (Affinity Capture-MS), ABHD5 (Affinity Capture-MS), HMOX2 (Affinity Capture-MS), KDM4A (Affinity Capture-MS), ABHD5 (Synthetic Lethality)

ESM2 similar proteins: A5GFX0, A8Y5H7, F7B909, O59707, P35200, P49675, P51557, P59095, P59096, P70114, Q03606, Q04006, Q05776, Q0V9N0, Q14849, Q16KN5, Q28996, Q29JQ0, Q4R5S9, Q54G07, Q54VC7, Q58DB0, Q5BKH5, Q5EA59, Q5RBI4, Q61542, Q6GM21, Q6NTS7, Q6P9U4, Q6TMK8, Q8GXB1, Q8TB40, Q8VD66, Q8VE85, Q8WTS1, Q92503, Q96N28, Q9CYY7, Q9DE06, Q9DEB4

Diamond homologs: A0A126P745, A8GCT3, A9W3H8, B0SY51, B1M5I5, B1ZB18, B7KWT4, C5B0U6, C7CM33, I6YC03, P07383, P0A3G2, P0A3G3, P0A3G4, P0DO69, P0DO70, P59336, P95276, Q1QBB9, Q5EE05, Q5QZC0, Q5RBI4, Q8U671, Q8WTS1, Q988D4, Q98C03, A1VUV0, A4JPX5, A5I3F5, A6TAC7, A7ZI96, A7ZWZ6, B1XBJ6, B2JQW2, B6HZX5, B7L505, B7M2Z7, B7MPB6, B7N8Q6, B7NK06

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

360 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	11
Uncertain significance	161
Likely benign	107
Benign	32

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2203346	NM_016006.6(ABHD5):c.700C>T (p.Arg234Ter)	Pathogenic
253640	GRCh37/hg19 3p22.1-21.31(chr3:41104508-44636698)x1	Pathogenic
2694886	NM_016006.6(ABHD5):c.285del (p.Phe95fs)	Pathogenic
2734489	NM_016006.6(ABHD5):c.507-1G>A	Pathogenic
3236337	NM_016006.6(ABHD5):c.889C>T (p.Arg297Ter)	Pathogenic
3236338	ABHD5, ARG184TER	Pathogenic
3660533	NM_016006.6(ABHD5):c.774del (p.Ser258fs)	Pathogenic
4075899	GRCh37/hg19 3p21.33(chr3:43726994-43765143)x1	Pathogenic
523801	NM_016006.6(ABHD5):c.340C>T (p.Arg114Ter)	Pathogenic
524159	NM_016006.6(ABHD5):c.588_591del (p.Trp197fs)	Pathogenic
5347	NM_016006.6(ABHD5):c.774-1G>A	Pathogenic
5348	NM_016006.6(ABHD5):c.98C>G (p.Ser33Ter)	Pathogenic
5349	NM_016006.6(ABHD5):c.134-2A>G	Pathogenic
5350	NM_016006.6(ABHD5):c.389A>C (p.Gln130Pro)	Pathogenic
5352	NM_016006.6(ABHD5):c.594dup (p.Arg199fs)	Pathogenic
5353	NM_016006.6(ABHD5):c.778G>A (p.Glu260Lys)	Pathogenic
5354	NM_016006.6(ABHD5):c.46_47del (p.Arg16fs)	Pathogenic
562760	GRCh37/hg19 3p24.3-21.31(chr3:16923595-45249923)x2,3	Pathogenic
619125	NM_016006.6(ABHD5):c.934C>T (p.Arg312Ter)	Pathogenic
812597	NM_016006.6(ABHD5):c.811G>A (p.Gly271Arg)	Pathogenic
973467	NM_016006.6(ABHD5):c.550C>T (p.Arg184Ter)	Pathogenic
977526	NM_016006.6(ABHD5):c.810T>A (p.Tyr270Ter)	Pathogenic
996655	NM_016006.6(ABHD5):c.836del (p.Gln279fs)	Pathogenic
1697083	NM_016006.6(ABHD5):c.960+5G>A	Likely pathogenic
2203347	NM_016006.6(ABHD5):c.773+1del	Likely pathogenic
253356	GRCh37/hg19 3p22.2-21.31(chr3:37028313-49929220)x3	Likely pathogenic
2574453	NM_016006.6(ABHD5):c.752A>C (p.His251Pro)	Likely pathogenic
2627677	NC_000003.12:g.43688574_43691430del	Likely pathogenic
2627793	NC_000003.11:g.(?43743409)(43744194_?)del	Likely pathogenic
2628741	NM_016006.6(ABHD5):c.133+1G>A	Likely pathogenic

SpliceAI

1205 predictions. Top by Δscore:

Variant	Effect	Δscore
3:43691035:GAGAG:G	donor_gain	1.0000
3:43691037:GAG:G	donor_gain	1.0000
3:43691038:AGGTA:A	donor_loss	1.0000
3:43691040:G:GC	donor_loss	1.0000
3:43691040:G:GG	donor_gain	1.0000
3:43691041:T:G	donor_loss	1.0000
3:43699362:G:GG	donor_gain	1.0000
3:43702584:CAAGG:C	donor_loss	1.0000
3:43702586:AGGTA:A	donor_loss	1.0000
3:43702589:T:A	donor_loss	1.0000
3:43711707:AG:A	acceptor_gain	1.0000
3:43711708:GG:G	acceptor_gain	1.0000
3:43711862:TGG:T	donor_loss	1.0000
3:43711864:G:GG	donor_gain	1.0000
3:43711864:G:T	donor_loss	1.0000
3:43711865:TGAG:T	donor_loss	1.0000
3:43711866:GAGT:G	donor_loss	1.0000
3:43717663:C:A	acceptor_gain	1.0000
3:43717667:AAAGT:A	acceptor_gain	1.0000
3:43717858:G:GG	donor_gain	1.0000
3:43718438:TCCA:T	acceptor_loss	1.0000
3:43718440:CA:C	acceptor_loss	1.0000
3:43718441:A:AC	acceptor_loss	1.0000
3:43718441:A:AG	acceptor_gain	1.0000
3:43718441:AG:A	acceptor_gain	1.0000
3:43718442:G:GA	acceptor_loss	1.0000
3:43718442:G:GG	acceptor_gain	1.0000
3:43718442:GG:G	acceptor_gain	1.0000
3:43718442:GGCT:G	acceptor_gain	1.0000
3:43702408:ATT:A	acceptor_gain	0.9900

AlphaMissense

2269 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:43702352:T:A	W91R	0.999
3:43702352:T:C	W91R	0.999
3:43711737:T:A	W179R	0.999
3:43711737:T:C	W179R	0.999
3:43711740:G:C	G180R	0.999
3:43711791:T:A	W197R	0.999
3:43711791:T:C	W197R	0.999
3:43711846:G:C	R215T	0.999
3:43711846:G:T	R215M	0.999
3:43717676:A:T	E260V	0.999
3:43717781:G:A	G295D	0.999
3:43702415:T:C	F112L	0.998
3:43702417:T:A	F112L	0.998
3:43702417:T:G	F112L	0.998
3:43702424:A:C	S115R	0.998
3:43702426:T:A	S115R	0.998
3:43702426:T:G	S115R	0.998
3:43702493:T:A	W138R	0.998
3:43702493:T:C	W138R	0.998
3:43711847:G:C	R215S	0.998
3:43711847:G:T	R215S	0.998
3:43711855:G:A	G218E	0.998
3:43714971:G:C	R229T	0.998
3:43717673:G:A	G259D	0.998
3:43702335:G:A	G85E	0.997
3:43702412:G:C	G111R	0.997
3:43702413:G:A	G111D	0.997
3:43702419:G:A	G113E	0.997
3:43702532:G:T	G151W	0.997
3:43702548:G:A	G156E	0.997

dbSNP variants (sampled 300 via entrez): RS1000038930 (3:43727570 G>A), RS1000094202 (3:43714466 G>A), RS1000171565 (3:43691336 C>A,G,T), RS1000226450 (3:43702782 A>G,T), RS1000257575 (3:43703094 A>G), RS1000291717 (3:43695596 C>T), RS1000386915 (3:43702737 A>G), RS1000407708 (3:43716690 T>G), RS1000421825 (3:43714677 T>A), RS1000487070 (3:43719655 A>G), RS1000583607 (3:43690375 T>A), RS1000627066 (3:43716363 TA>T), RS1000636562 (3:43726085 C>T), RS1000769126 (3:43731688 C>T), RS1000836106 (3:43709273 A>G)

Disease associations

OMIM: gene MIM:604780 | disease phenotypes: MIM:275630, MIM:614830

GenCC curated gene-disease

Disease	Classification	Inheritance
Dorfman-Chanarin disease	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Dorfman-Chanarin disease	Definitive	AR

Mondo (2): Dorfman-Chanarin disease (MONDO:0010155), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (MONDO:0013904)

Orphanet (2): Neutral lipid storage disease with ichthyosis (Orphanet:98907), Walker-Warburg syndrome (Orphanet:899)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000232	Everted lower lip vermilion
HP:0000385	Small earlobe
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000523	Subcapsular cataract
HP:0000639	Nystagmus
HP:0000656	Ectropion
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001397	Hepatic steatosis
HP:0001413	Micronodular cirrhosis
HP:0001513	Obesity
HP:0001596	Alopecia
HP:0001638	Cardiomyopathy
HP:0001871	Abnormality of blood and blood-forming tissues
HP:0001911	Abnormal granulocyte morphology
HP:0001946	Ketosis
HP:0002155	Hypertriglyceridemia
HP:0002240	Hepatomegaly
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0002922	Increased CSF protein concentration
HP:0003198	Myopathy
HP:0003458	EMG: myopathic abnormalities
HP:0003547	Shoulder girdle muscle weakness

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002740_64	Inflammatory skin disease	4.000000e-10
GCST007325_234	General risk tolerance (MTAG)	4.000000e-09
GCST90020024_1140	A body shape index	1.000000e-09
GCST90020025_1939	Waist-to-hip ratio adjusted for BMI	7.000000e-10
GCST90020027_170	Waist-hip index	5.000000e-10
GCST90020029_1168	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3883313 (PROTEIN-PROTEIN INTERACTION), CHEMBL3885501 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 279,056 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL388590	BENZBROMARONE	4	8,245
CHEMBL456	ETHACRYNIC ACID	4	20,004
CHEMBL590	MENADIONE	4	21,034
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL12856	INAMRINONE	4	9,690
CHEMBL140	CURCUMIN	3	93,882
CHEMBL51085	EBSELEN	3	13,237

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

64 potent at pChembl≥5 of 88 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.96	IC50	1101	nM	EBSELEN
5.95	IC50	1123	nM	CHEMBL1565221
5.91	IC50	1227	nM	CHEMBL1565221
5.83	IC50	1484	nM	CHEMBL17201
5.82	IC50	1520	nM	CHEMBL17201
5.79	IC50	1622	nM	DISULFIRAM
5.73	IC50	1868	nM	TPCK
5.72	IC50	1901	nM	TPCK
5.68	IC50	2068	nM	CHEMBL1500987
5.66	IC50	2207	nM	CHEMBL1535633
5.64	IC50	2269	nM	CHEMBL1500987
5.64	IC50	2278	nM	CHEMBL1369296
5.55	IC50	2798	nM	CHEMBL1535633
5.52	IC50	2992	nM	CHEMBL1414703
5.51	IC50	3103	nM	CHEMBL1369296
5.50	IC50	3170	nM	CHEMBL1598561
5.48	IC50	3300	nM	CHEMBL1462108
5.48	IC50	3339	nM	CHEMBL1462108
5.48	IC50	3291	nM	CHEMBL1363719
5.47	IC50	3408	nM	CHEMBL1363719
5.47	IC50	3410	nM	EBSELEN
5.45	IC50	3573	nM	CHEMBL1598561
5.41	IC50	3906	nM	CHEMBL1352555
5.41	IC50	3912	nM	CHEMBL1352555
5.40	IC50	3942	nM	CHEMBL1414703
5.38	IC50	4194	nM	CHALCONE
5.38	IC50	4190	nM	ETHACRYNIC ACID
5.37	IC50	4245	nM	CHALCONE
5.36	IC50	4420	nM	CHEMBL1507428
5.36	IC50	4375	nM	CHEMBL1522846
5.35	IC50	4462	nM	CHEMBL1548890
5.33	IC50	4641	nM	CHEMBL1426508
5.32	IC50	4832	nM	ETHACRYNIC ACID
5.32	IC50	4803	nM	CHEMBL1498750
5.31	IC50	4850	nM	CHEMBL1498750
5.30	IC50	5052	nM	CHEMBL1256923
5.28	IC50	5240	nM	CHEMBL485636
5.28	IC50	5283	nM	CHEMBL1256923
5.25	IC50	5597	nM	CHEMBL485636
5.24	IC50	5718	nM	CHEMBL1522846
5.21	IC50	6238	nM	CHEMBL1507428
5.19	IC50	6443	nM	9,10-PHENANTHRENEQUINONE
5.17	IC50	6718	nM	CHEMBL1366427
5.17	IC50	6794	nM	CHEMBL1517036
5.17	IC50	6842	nM	CHEMBL1308170
5.16	IC50	6958	nM	CHEMBL1519501
5.16	IC50	6970	nM	CHEMBL1478754
5.16	IC50	6855	nM	CHEMBL1519501
5.16	IC50	6959	nM	DISULFIRAM
5.15	IC50	7133	nM	NIFEDIPINE

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
sodium arsenite	affects methylation, increases expression	3
Benzo(a)pyrene	increases expression	3
Cyclosporine	increases expression	3
Cadmium Chloride	increases abundance, increases expression	3
bisphenol A	increases methylation, affects cotreatment, increases expression	2
Cisplatin	decreases expression, affects expression, affects cotreatment	2
Dexamethasone	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
Aflatoxin B1	increases expression, decreases methylation	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
testosterone undecanoate	affects cotreatment, decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
2-chloroethyl ethyl sulfide	affects binding, decreases reaction	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1738098	Binding	PUBCHEM_BIOASSAY: Luminescence-based biochemical high throughput dose response assay for inhibitors of the interaction of the lipase co-activator protein, abhydrolase domain containing 5 (ABHD5) with perilipin-1 (PLIN1) (2K validation set).	PubChem BioAssay data set

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.