ABHD8

Summary

ABHD8 (abhydrolase domain containing 8, HGNC:23759) is a protein-coding gene on chromosome 19p13.11, encoding Protein ABHD8 (Q96I13). Negatively regulates NLRP3-driven inflammation.

This gene is upstream of, and in a head-to-head orientation with the gene for the mitochondrial ribosomal protein L34. The predicted protein contains alpha/beta hydrolase fold and secretory lipase domains.

Source: NCBI Gene 79575 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 55 total — 1 pathogenic
• MANE Select transcript: NM_024527

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23759
Approved symbol	ABHD8
Name	abhydrolase domain containing 8
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11743, MGC14280, MGC2512
Ensembl gene	ENSG00000127220
Ensembl biotype	protein_coding
OMIM	621036
Entrez	79575

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000247706, ENST00000593489, ENST00000594194, ENST00000927605, ENST00000951444

RefSeq mRNA: 1 — MANE Select: NM_024527 NM_024527

CCDS: CCDS12355

Canonical transcript exons

ENST00000247706 — 5 exons

Exon	Start	End
ENSE00000870976	17292131	17292831
ENSE00000870977	17294288	17294504
ENSE00000870978	17294675	17294845
ENSE00000870979	17300856	17301624
ENSE00001049929	17303242	17303425

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 96.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4999 / max 102.7830, expressed in 1718 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179852	7.3233	1690
179850	0.7545	443
179851	0.4221	255

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.59	gold quality
right frontal lobe	UBERON:0002810	95.97	gold quality
anterior cingulate cortex	UBERON:0009835	95.11	gold quality
cingulate cortex	UBERON:0003027	95.06	gold quality
prefrontal cortex	UBERON:0000451	94.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.62	gold quality
nucleus accumbens	UBERON:0001882	93.50	gold quality
amygdala	UBERON:0001876	93.20	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.04	gold quality
caudate nucleus	UBERON:0001873	92.79	gold quality
putamen	UBERON:0001874	92.73	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.36	gold quality
cerebellar hemisphere	UBERON:0002245	92.32	gold quality
cerebellar cortex	UBERON:0002129	92.29	gold quality
frontal cortex	UBERON:0001870	92.08	gold quality
neocortex	UBERON:0001950	92.01	gold quality
cerebellum	UBERON:0002037	91.08	gold quality
left testis	UBERON:0004533	91.08	gold quality
right testis	UBERON:0004534	90.56	gold quality
telencephalon	UBERON:0001893	90.19	gold quality
cerebral cortex	UBERON:0000956	90.08	gold quality
forebrain	UBERON:0001890	89.63	gold quality
brain	UBERON:0000955	89.07	gold quality
hypothalamus	UBERON:0001898	88.64	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.39	silver quality
temporal lobe	UBERON:0001871	88.27	gold quality
left adrenal gland cortex	UBERON:0035825	88.03	gold quality
left adrenal gland	UBERON:0001234	87.93	gold quality
right adrenal gland	UBERON:0001233	87.84	gold quality
testis	UBERON:0000473	87.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting ABHD8, 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-4283	100.00	66.42	2097
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-657	99.48	66.02	848
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-1237-5P	95.38	62.21	451
HSA-MIR-4488	95.38	62.00	443
HSA-MIR-4697-5P	95.38	61.72	457
HSA-MIR-7108-3P	94.37	64.79	183

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	abhd8b	ENSDARG00000076620
danio_rerio	abhd8a	ENSDARG00000103518
mus_musculus	Abhd8	ENSMUSG00000007950
rattus_norvegicus	Abhd8	ENSRNOG00000000054
drosophila_melanogaster	CG5704	FBGN0026570
drosophila_melanogaster	CG5707	FBGN0026593
drosophila_melanogaster	CG15879	FBGN0035309
drosophila_melanogaster	CG15820	FBGN0035312
drosophila_melanogaster	CG11309	FBGN0037070
drosophila_melanogaster	CG7632	FBGN0037071
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): ABHD5 (ENSG00000011198), ABHD4 (ENSG00000100439), EPHX3 (ENSG00000105131), ABHD11 (ENSG00000106077), MEST (ENSG00000106484), ABHD14B (ENSG00000114779), EPHX2 (ENSG00000120915), BPHL (ENSG00000137274), ABHD6 (ENSG00000163686), EPHX4 (ENSG00000172031), SERHL2 (ENSG00000183569), ABHD14A (ENSG00000248487)

Protein

Protein identifiers

Protein ABHD8 — Q96I13 (reviewed: Q96I13)

Alternative names: Alpha/beta hydrolase domain-containing protein 8

All UniProt accessions (4): Q96I13, B2C6G3, M0QX40, M0QZA8

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates NLRP3-driven inflammation. Promotes NLRP3 degradation through the chaperone-mediated autophagy (CMA) pathway, hence attenuating inflammasome activation and IL1B secretion. Acts by recruiting palmitoyltransferase ZDHHC12 to NLRP3, facilitating NLRP3 palmitoylation and subsequent degradation.

Subunit / interactions. Interacts with NLRP3 (via NACHT and LLR domains); this interaction is enhanced in the presence of NLRP3 inflammasome inducers, such as ATP, nigericin, silica, or alum. Interacts with ZDHHC12. (Microbial infection) Interacts with SARS-CoV-2 nucleoprotein N; this interaction disrupts the NLRP3-ABHD8 association, enhancing NLRP3 stability, ultimately leading to increased inflammasome activation.

Subcellular location. Cytoplasm.

Similarity. Belongs to the AB hydrolase superfamily.

RefSeq proteins (1): NP_078803* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR000639	Epox_hydrolase-like	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF00561

UniProt features (10 total): active site 3, region of interest 2, compositionally biased region 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96I13-F1	79.84	0.57

Functional residue map

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

Catalytic / active sites (3): 252 (charge relay system); 370 (charge relay system); 398 (charge relay system)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, RACCACAR_AML_Q6, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, BOYLAN_MULTIPLE_MYELOMA_D_DN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_HOMEOSTASIS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (4): phosphatidic acid biosynthetic process (GO:0006654), inflammatory response (GO:0006954), lipid homeostasis (GO:0055088), negative regulation of NLRP3 inflammasome complex assembly (GO:1900226)

GO Molecular Function (5): lysophosphatidic acid acyltransferase activity (GO:0042171), carboxylic ester hydrolase activity (GO:0052689), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasm (GO:0005737), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
defense response	1
chemical homeostasis	1
negative regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
negative regulation of inflammasome-mediated signaling pathway	1
regulation of NLRP3 inflammasome complex assembly	1
lysophospholipid acyltransferase activity	1
hydrolase activity, acting on ester bonds	1
molecular_function	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABHD8	ANKLE1	Q8NAG6	718
ABHD8	ABHD18	Q0P651	648
ABHD8	BABAM1	Q9NWV8	620
ABHD8	ABHD16B	Q9H3Z7	595
ABHD8	ABHD13	Q7L211	535
ABHD8	ABHD11	Q8NFV4	532
ABHD8	ABHD14A	Q9BUJ0	532
ABHD8	ABHD12B	Q7Z5M8	527
ABHD8	MRPL34	Q9BQ48	510
ABHD8	ABHD15	Q6UXT9	490
ABHD8	ABHD2	P08910	489
ABHD8	ABHD10	Q9NUJ1	481
ABHD8	ABHD1	Q96SE0	475
ABHD8	OCEL1	Q9H607	455
ABHD8	ABHD4	Q8TB40	455

IntAct

11 interactions, top by confidence:

A	B	Type	Score
FNDC3B	ABHD8	psi-mi:“MI:0915”(physical association)	0.560
ZNF410	ABHD8	psi-mi:“MI:0915”(physical association)	0.560
LMO2	APBB1	psi-mi:“MI:0914”(association)	0.350
LMO2	POLR2D	psi-mi:“MI:0914”(association)	0.350
OR52N5	ART1	psi-mi:“MI:0914”(association)	0.350
ABHD8	RIC8B	psi-mi:“MI:0914”(association)	0.350
FNDC3B	ABHD8	psi-mi:“MI:0915”(physical association)	0.000
ZNF410	ABHD8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): ABHD8 (Affinity Capture-MS), ABHD8 (Two-hybrid), ABHD8 (Two-hybrid), ABHD8 (Affinity Capture-MS), ABHD8 (Affinity Capture-MS), ABHD8 (Positive Genetic), ABHD8 (Affinity Capture-MS), ABHD8 (Affinity Capture-MS), YBX2 (Affinity Capture-MS), RIC8B (Affinity Capture-MS), NLRP3 (Affinity Capture-Western), NLRP3 (FRET), ABHD8 (Affinity Capture-Western), ABHD8 (Affinity Capture-Western), ABHD8 (Affinity Capture-Western)

ESM2 similar proteins: D3YXJ0, D3ZVP7, E9PUQ8, M9MRI4, O00562, O14827, O35954, O70143, O75689, O76902, O95248, P08240, P11862, P34657, Q02280, Q05B78, Q15057, Q16760, Q17QP1, Q29RQ5, Q2I6J0, Q2KI13, Q38JA7, Q4R584, Q505D9, Q5F3R2, Q5RFL4, Q5U2N3, Q5W7F2, Q5ZK62, Q64398, Q68FU1, Q6NNF2, Q6NVJ5, Q6ZPE2, Q6ZTA4, Q810J8, Q86XP1, Q8C7M3, Q8VCM3

Diamond homologs: A0A1L5BTC1, A0A242M8J4, A1KLS7, A4JPX5, A5U5S9, A7YY28, A9W3H8, B0SW62, B0SY51, B2HJU9, B2JQW2, B4RF90, B7KWT4, B8H1Q3, C1AF48, C7TMK0, D4Z2G1, I6YC03, I6YGS0, O05235, O05691, O31158, O31168, O32234, P0A3G2, P0A3G3, P0A3G4, P0DO68, P0DO69, P0DO70, P19076, P22862, P23106, P25026, P27652, P29715, P34913, P34914, P49323, P59336

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	49
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
424641	GRCh37/hg19 19p13.12-13.11(chr19:15970389-17893528)x1	Pathogenic

SpliceAI

1575 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17292827:AGGAT:A	acceptor_gain	1.0000
19:17292828:GGAT:G	acceptor_gain	1.0000
19:17292830:ATCT:A	acceptor_loss	1.0000
19:17292831:TCT:T	acceptor_loss	1.0000
19:17292832:C:CC	acceptor_gain	1.0000
19:17292852:AAGG:A	donor_loss	1.0000
19:17292853:AGGTA:A	donor_loss	1.0000
19:17292854:GGTA:G	donor_loss	1.0000
19:17292855:GTA:G	donor_loss	1.0000
19:17292856:T:G	donor_loss	1.0000
19:17294307:T:TA	donor_gain	1.0000
19:17294327:AT:A	donor_gain	1.0000
19:17294328:T:C	donor_gain	1.0000
19:17300852:TTA:T	donor_loss	1.0000
19:17300854:A:AC	donor_gain	1.0000
19:17300854:AC:A	donor_gain	1.0000
19:17300854:ACC:A	donor_gain	1.0000
19:17300855:C:A	donor_loss	1.0000
19:17300855:C:CC	donor_gain	1.0000
19:17300855:CC:C	donor_gain	1.0000
19:17300855:CCC:C	donor_gain	1.0000
19:17300855:CCCG:C	donor_gain	1.0000
19:17300855:CCCGT:C	donor_gain	1.0000
19:17309654:GATG:G	donor_gain	1.0000
19:17309655:ATGG:A	donor_loss	1.0000
19:17309656:TGGT:T	donor_loss	1.0000
19:17309657:GGT:G	donor_loss	1.0000
19:17309663:G:GT	donor_gain	1.0000
19:17292829:GAT:G	acceptor_gain	0.9900
19:17292830:AT:A	acceptor_gain	0.9900

AlphaMissense

2835 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17292736:G:C	F415L	1.000
19:17292736:G:T	F415L	1.000
19:17292738:A:G	F415L	1.000
19:17292787:G:C	H398Q	1.000
19:17292787:G:T	H398Q	1.000
19:17292789:G:A	H398Y	1.000
19:17292789:G:C	H398D	1.000
19:17294328:T:A	D370V	1.000
19:17294328:T:G	D370A	1.000
19:17294329:C:A	D370Y	1.000
19:17294329:C:G	D370H	1.000
19:17294337:C:T	G367D	1.000
19:17294343:A:T	V365D	1.000
19:17294349:A:G	L363P	1.000
19:17294396:C:A	W347C	1.000
19:17294396:C:G	W347C	1.000
19:17294398:A:G	W347R	1.000
19:17294398:A:T	W347R	1.000
19:17294495:G:C	F314L	1.000
19:17294495:G:T	F314L	1.000
19:17294497:A:G	F314L	1.000
19:17294833:G:C	C258W	1.000
19:17294834:C:T	C258Y	1.000
19:17294835:A:G	C258R	1.000
19:17300856:C:A	G254V	1.000
19:17300856:C:T	G254D	1.000
19:17300857:C:G	G254R	1.000
19:17300863:A:G	S252P	1.000
19:17300868:C:T	G250D	1.000
19:17300936:G:C	F227L	1.000

dbSNP variants (sampled 300 via entrez): RS1000101771 (19:17303356 C>G,T), RS1000392743 (19:17291692 T>C), RS1000605234 (19:17297394 C>T), RS1001048620 (19:17301212 G>A,C,T), RS1001053746 (19:17292194 C>T), RS1001164710 (19:17302877 G>C), RS1001664500 (19:17297350 C>A,T), RS1002558378 (19:17293216 C>T), RS1002652876 (19:17299888 C>A), RS1002871148 (19:17304054 G>A), RS1002898696 (19:17301276 G>A), RS1003027828 (19:17299240 C>A,G), RS1003102240 (19:17296350 G>A), RS1003201231 (19:17300358 C>T), RS1003232499 (19:17299991 G>A,C)

Disease associations

OMIM: gene MIM:621036 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000801_1	Breast cancer	2.000000e-09
GCST007394_2	Mitochondrial DNA copy number	1.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006312	mitochondrial DNA measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases methylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Lead	affects expression	1
Mustard Gas	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Toluene	decreases expression, increases methylation	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1
Raloxifene Hydrochloride	affects response to substance	1
S-Nitrosoglutathione	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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