ABHD5

Chr 3AR

abhydrolase domain containing 5, lysophosphatidic acid acyltransferase

Also known as: CGI58, IECN2, NCIE2

NCBI Gene: 51099 ENSG00000011198 UniProt: Q8WTS1 OMIM: 604780

The encoded protein functions as a coenzyme A-dependent lysophosphatidic acid acyltransferase involved in phosphatidic acid biosynthesis and regulation of triacylglycerol storage through activation of phospholipase PNPLA2. Mutations cause Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation characterized by systemic lipid accumulation affecting skin, liver, muscle, and other organs. Inheritance is autosomal recessive.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.981 OMIM phenotype

Clinical Summary— ABHD5

🧬

Gene-Disease Validity (ClinGen)

Dorfman-Chanarin disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

34 unique Pathogenic / Likely Pathogenic· 161 VUS of 361 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.98LOEUF

pLI 0.000

Z-score 1.63

OE 0.62 (0.40–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.47Z-score

OE missense 0.90 (0.79–1.03)

166 obs / 184.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.40–0.98)

0≤0.351.4

Missense OE?0.90 (0.79–1.03)

0≤0.61.4

Synonymous OE?1.31

0≤1.21.6

LoF obs/exp: 13 / 21.1Missense obs/exp: 166 / 184.1Syn Z: -1.98

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveABHD5-related ichthyotic neutral lipid storage diseaseLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6648th %ile

GOF

0.5661th %ile

LOF

0.3066th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

361 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic13

VUS161

Likely Benign116

Benign33

Conflicting11

Pathogenic

Likely Pathogenic

161

VUS

116

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	17	3	1	0	21
Likely Pathogenic	8	2	3	0	13
VUS	0	96	63	2	161
Likely Benign	0	7	51	58	116
Benign	0	1	30	2	33
Conflicting	—				11
Total	25	109	148	62	355

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap ABHD5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →