ABHD12

Chr 20AR

abhydrolase domain containing 12, lysophospholipase

Also known as: ABHD12A, BEM46L2, C20orf22, PHARC, dJ965G21.2, hABHD12

The protein encoded by this gene is a lysophosphatidylserine lipase that hydrolyzes signaling lipids regulating neurological processes and also degrades the endocannabinoid 2-arachidonoylglycerol. Mutations cause PHARC syndrome (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract), a multisystem neurodegenerative disorder with autosomal recessive inheritance. The gene shows relatively high tolerance to loss-of-function variants (LOEUF 0.763), suggesting complete loss of function may be required for disease manifestation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.761 OMIM phenotype
Clinical SummaryABHD12
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Gene-Disease Validity (ClinGen)
PHARC syndrome · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.000
Z-score 2.47
OE 0.47 (0.300.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.19Z-score
OE missense 0.96 (0.861.08)
210 obs / 218.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.47 (0.300.76)
00.351.4
Missense OE0.96 (0.861.08)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 12 / 25.5Missense obs/exp: 210 / 218.1Syn Z: -0.07
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveABHD12-related polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataractLOFAR

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

DN
0.6937th %ile
GOF
0.5856th %ile
LOF
0.2777th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ABHD12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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