Curated summary · agent-written · kb/genes/curated/hgnc_21396.md

All 12 claims checked against the KB draft

ABHD5 across dismech

ABHD5 (abhydrolase domain containing 5, lysophosphatidic acid acyltransferase) is named by 1 disorder entry: Dorfman-Chanarin Disease.

Normal function

ai-gene-review gives ABHD5's core molecular function as lipase activator activity, acting in positive regulation of triglyceride catabolic process; and lipid homeostasis at the lipid droplet; and cytosol. ABHD5 is the non-catalytic co-activator of adipose triglyceride lipase (PNPLA2/ATGL); the review treats the reported intrinsic acyltransferase activity as unsupported.

Causative record

Dorfman-Chanarin Disease types ABHD5 as causative with a germline variant origin, and ClinGen rates the gene-disease pair definitive. The gene sits on the node ABHD5/CGI-58 Deficiency and Loss of ATGL Co-activation.

Where the layers agree and disagree

The KB's ABHD5 nodes and the ai-gene-review core functions share positive regulation of triglyceride catabolic process: the disease entry marks it decreased, the review describes it as the normal role.

The Triglyceride Storage Disease Type 1 entry no longer names ABHD5. Its MONDO term maps to the historical OMIM 190420 adipose-lipolysis phenotype, which has no known gene, so the ABHD5 content it used to carry now lives in the Dorfman-Chanarin Disease entry.

Underlined values are claims re-computed from the knowledge base each time this page is built. The tables below are the source of truth.

Normal function · from ai-gene-review (Q8WTS1, commit 79fe13b38970) · AI-generated, not KB evidence

ABHD5 (CGI-58) is a lipid-droplet-associated regulatory protein with an alpha/beta-hydrolase fold. It binds and activates adipose triglyceride lipase (ATGL/PNPLA2), promoting mobilization of stored triacylglycerol. Its distribution between cytosol and lipid droplets helps couple partner access to lipid metabolism. In epidermal lipid synthesis, ABHD5 also promotes PNPLA1 recruitment to droplets and enhances formation of omega-O-acylceramides needed for the skin barrier. Biallelic loss-of-function variants cause neutral lipid storage disease with ichthyosis, also called Chanarin-Dorfman syndrome. ABHD5-dependent HDAC4 cleavage has also been reconstituted in vitro; the extent of this activity in endogenous human tissues remains unresolved.

Binds and activates ATGL/PNPLA2 at lipid droplets, accelerating hydrolysis of stored triglycerides and maintaining neutral-lipid balance. A soluble cytosolic pool and regulated access to droplet-associated partners support this function. ABHD5 provides the regulatory activity; ATGL supplies the triglyceride-hydrolysis chemistry.

molecular function: lipase activator activity · directly involved in: positive regulation of triglyceride catabolic process; lipid homeostasis · locations: lipid droplet; cytosol

Promotes PNPLA1 recruitment and stimulation at lipid droplets during epidermal omega-O-acylceramide synthesis. Human construct experiments separate deficient ABHD5–PNPLA1 association from defective perilipin-dependent droplet targeting; forced membrane co-localization rescues the tested disease variants in proteoliposomes. ABHD5 provides spatial and regulatory support while PNPLA1 catalyzes transacylation. The effects depend on the reconstitution context, and this role is not expressed as intrinsic ABHD5 acyltransferase or lipase activity.

directly involved in: lipid homeostasis · locations: lipid droplet

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Dorfman-Chanarin Disease	causative germline CLINGEN: definitive	mechanism: ABHD5/CGI-58 Deficiency and Loss of ATGL Co-activation

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
Dorfman-Chanarin disease MONDO:0010155	AR	Definitive 2022-08-02	Dorfman-Chanarin Disease causative