ABHD18

Summary

ABHD18 (abhydrolase domain containing 18, HGNC:26111) is a protein-coding gene on chromosome 4q28.2, encoding Protein ABHD18 (Q0P651).

Located in mitochondrion.

Source: NCBI Gene 80167 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 102 total — 9 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_001358451

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26111
Approved symbol	ABHD18
Name	abhydrolase domain containing 18
Location	4q28.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21106
Ensembl gene	ENSG00000164074
Ensembl biotype	protein_coding
Entrez	80167

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 3 nonsense_mediated_decay

ENST00000388795, ENST00000444616, ENST00000473040, ENST00000513371, ENST00000611882, ENST00000645843, ENST00000870237, ENST00000870238, ENST00000870239, ENST00000870240, ENST00000870241, ENST00000870242, ENST00000870243, ENST00000870244, ENST00000870245, ENST00000870246, ENST00000918517, ENST00000957331, ENST00000957332, ENST00000957333, ENST00000957334, ENST00000957335, ENST00000957336, ENST00000957337

RefSeq mRNA: 19 — MANE Select: NM_001358451 NM_001039717, NM_001319305, NM_001319306, NM_001319307, NM_001358451, NM_001358454, NM_001366037, NM_001366038, NM_001366039, NM_001366040, NM_001366041, NM_001366042, NM_001366043, NM_001366044, NM_001366045, NM_001366046, NM_001366047, NM_001366048, NM_025097

CCDS: CCDS87261

Canonical transcript exons

ENST00000645843 — 13 exons

Exon	Start	End
ENSE00001503983	128011673	128011700
ENSE00001503984	128009107	128009191
ENSE00001503986	127989721	127989821
ENSE00002480182	128017363	128017501
ENSE00003483490	128030510	128030672
ENSE00003518996	128028475	128028853
ENSE00003535116	127984339	127984423
ENSE00003538753	128020080	128020169
ENSE00003542400	128008920	128008998
ENSE00003561216	127982939	127983047
ENSE00003611198	128021137	128021238
ENSE00003819262	128035762	128039953
ENSE00003912647	127965406	127965606

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 88.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.4925 / max 169.5902, expressed in 1807 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49614	9.7741	1774
49613	2.5161	1270
49611	1.5187	676
49612	1.1025	646
203334	0.4232	217
49610	0.1579	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	88.83	gold quality
jejunal mucosa	UBERON:0000399	86.57	gold quality
jejunum	UBERON:0002115	86.52	gold quality
cerebellar vermis	UBERON:0004720	84.62	silver quality
adrenal tissue	UBERON:0018303	84.38	gold quality
monocyte	CL:0000576	84.21	gold quality
mononuclear cell	CL:0000842	83.89	gold quality
duodenum	UBERON:0002114	83.83	gold quality
calcaneal tendon	UBERON:0003701	83.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.70	gold quality
renal medulla	UBERON:0000362	83.45	gold quality
biceps brachii	UBERON:0001507	83.45	gold quality
leukocyte	CL:0000738	83.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.24	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.20	gold quality
superior surface of tongue	UBERON:0007371	83.06	gold quality
body of pancreas	UBERON:0001150	82.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.43	gold quality
endothelial cell	CL:0000115	82.26	gold quality
right lobe of liver	UBERON:0001114	81.90	gold quality
tendon	UBERON:0000043	81.70	gold quality
pylorus	UBERON:0001166	81.51	gold quality
cardia of stomach	UBERON:0001162	81.22	gold quality
muscle of leg	UBERON:0001383	81.04	gold quality
cardiac ventricle	UBERON:0002082	81.02	gold quality
pancreas	UBERON:0001264	81.00	gold quality
heart left ventricle	UBERON:0002084	80.97	gold quality
liver	UBERON:0002107	80.89	gold quality
corpus callosum	UBERON:0002336	80.80	gold quality
tonsil	UBERON:0002372	80.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.13

Regulation

Is transcription factor: no

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	abhd18	ENSDARG00000101961
mus_musculus	Abhd18	ENSMUSG00000037818
rattus_norvegicus	Abhd18	ENSRNOG00000013692
drosophila_melanogaster	CG32112	FBGN0052112
caenorhabditis_elegans	C54G4.7	WBGENE00008317

Protein

Protein identifiers

Protein ABHD18 — Q0P651 (reviewed: Q0P651)

Alternative names: Alpha/beta hydrolase domain-containing protein 18

All UniProt accessions (5): A0A2R8YEZ0, B7WP89, D6RD85, D6RGX5, Q0P651

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the AB hydrolase superfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q0P651-1	1	yes
Q0P651-2	2
Q0P651-3	3
Q0P651-4	4

RefSeq proteins (19): NP_001034806, NP_001306234, NP_001306235, NP_001306236, NP_001345380, NP_001345383, NP_001352966, NP_001352967, NP_001352968, NP_001352969, NP_001352970, NP_001352971, NP_001352972, NP_001352973, NP_001352974, NP_001352975, NP_001352976, NP_001352977, NP_079373 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019149	ABHD18	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF09752

UniProt features (9 total): splice variant 4, glycosylation site 2, signal peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0P651-F1	80.82	0.61

Functional residue map

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

Glycosylation sites (2): 282, 307

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, FEVR_CTNNB1_TARGETS_UP, chr4q28, JAK2_DN.V1_DN, ATF6_TARGET_GENES, BANP_TARGET_GENES, DYRK1A_TARGET_GENES, HMG20B_TARGET_GENES, IRF5_TARGET_GENES, SNAI1_TARGET_GENES, MIR8485, MIR3662

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): extracellular region (GO:0005576), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABHD18	ABHD8	Q96I13	648
ABHD18	SPMIP10	Q6ZNM6	645
ABHD18	ABHD11	Q8NFV4	581
ABHD18	ABHD16B	Q9H3Z7	533
ABHD18	ABHD4	Q8TB40	503
ABHD18	MFSD8	Q8NHS3	502
ABHD18	ABHD2	P08910	478
ABHD18	ABHD14A	Q9BUJ0	475
ABHD18	ABHD15	Q6UXT9	468
ABHD18	ABHD12B	Q7Z5M8	465
ABHD18	COX7C	P15954	457
ABHD18	ABHD13	Q7L211	453
ABHD18	ABHD1	Q96SE0	449
ABHD18	KIAA0408	Q6ZU52	445
ABHD18	LARP1B	Q659C4	436

IntAct

41 interactions, top by confidence:

A	B	Type	Score
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
VSIG4	TCAF2	psi-mi:“MI:0914”(association)	0.530
CD79A	METTL15	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
ABHD18	HSPD1	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
YBEY	NME4	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
PDCD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
GLMP	RTL8C	psi-mi:“MI:0914”(association)	0.350
YBEY	NUDT19	psi-mi:“MI:0914”(association)	0.350
IMPDH1	LCMT2	psi-mi:“MI:0914”(association)	0.350
PRIMPOL	ECI2	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
CSNK2A2	VWA8	psi-mi:“MI:0914”(association)	0.350
SRP19	RPS3A	psi-mi:“MI:0914”(association)	0.350
SRP72	RPS3A	psi-mi:“MI:0914”(association)	0.350
ABTB2	IFT56	psi-mi:“MI:0914”(association)	0.350
RAMP2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PFDN5	GTPBP10	psi-mi:“MI:0914”(association)	0.350
P2RY10	POTEF	psi-mi:“MI:0914”(association)	0.350
GPR182	METTL15	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): SELO (Affinity Capture-MS), C4orf29 (Affinity Capture-MS), SELO (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), C4orf29 (Affinity Capture-MS), C4orf29 (Affinity Capture-MS), C4orf29 (Affinity Capture-MS), C4orf29 (Affinity Capture-MS), MGAT5B (Affinity Capture-MS), LAMP2 (Affinity Capture-MS), C4orf29 (Affinity Capture-MS), C4orf29 (Affinity Capture-MS), C4orf29 (Affinity Capture-MS), C4orf29 (Affinity Capture-MS), TOR1AIP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S3ZP85, A7XDQ9, B5X561, D6WMX4, E7BQV0, F4HZK4, F4IY62, F4J117, F4J7S8, F4JZJ2, F4K6D3, H2KZ86, O22267, O22977, O60502, O75460, P53264, P56695, Q0P651, Q0WUG6, Q0WVZ1, Q10MI0, Q2TBM9, Q3U213, Q501H5, Q5RD58, Q5SNQ7, Q5XVJ4, Q6AUQ7, Q6AX59, Q700D5, Q7Y220, Q8GXC6, Q8GYY7, Q8LFX7, Q8VIJ5, Q93VJ2, Q94BQ5, Q96JX3, Q9C5Q8

Diamond homologs: Q0P651, Q4V7A8, Q8C1A9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	2
Uncertain significance	60
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1328453	GRCh37/hg19 4q26-28.3(chr4:114872547-138005267)x1	Pathogenic
145990	GRCh38/hg38 4q28.1-28.3(chr4:125118620-132773079)x1	Pathogenic
1527114	GRCh37/hg19 4q24-31.21(chr4:104715235-145252595)	Pathogenic
1527119	GRCh37/hg19 4q26-28.2(chr4:116888785-129649979)	Pathogenic
155140	GRCh38/hg38 4q26-28.3(chr4:117351881-133565667)x1	Pathogenic
4846767	GRCh38/hg38 4q28.1-28.2(chr4:127842022-127987078)x1	Pathogenic
560144	Single allele	Pathogenic
562959	GRCh37/hg19 4q26-28.2(chr4:116307857-129302960)x1	Pathogenic
58033	GRCh38/hg38 4q22.3-28.3(chr4:96092893-136410207)x3	Pathogenic
2429312	NC_000004.11:g.(128878748_128886226)(128887140?)del	Likely pathogenic
4279432	GRCh37/hg19 4q28.1-31.21(chr4:125166237-142987037)x1	Likely pathogenic

SpliceAI

2233 predictions. Top by Δscore:

Variant	Effect	Δscore
4:127966100:G:GT	donor_gain	1.0000
4:127984332:A:AG	acceptor_gain	1.0000
4:127984333:T:G	acceptor_gain	1.0000
4:127984337:A:AG	acceptor_gain	1.0000
4:127984338:G:GG	acceptor_gain	1.0000
4:127984338:GA:G	acceptor_gain	1.0000
4:128008995:TCATG:T	donor_loss	1.0000
4:128008998:TGTAA:T	donor_loss	1.0000
4:128008999:G:GG	donor_gain	1.0000
4:128008999:GT:G	donor_loss	1.0000
4:128009000:T:A	donor_loss	1.0000
4:128017354:T:TA	acceptor_gain	1.0000
4:128021136:GGGT:G	acceptor_gain	1.0000
4:128021234:GTGGA:G	donor_gain	1.0000
4:128021236:GGA:G	donor_gain	1.0000
4:128021237:GA:G	donor_gain	1.0000
4:128021237:GAG:G	donor_gain	1.0000
4:128021239:G:GG	donor_gain	1.0000
4:127965602:GGCCA:G	donor_gain	0.9900
4:127965603:GCCA:G	donor_gain	0.9900
4:127965603:GCCAG:G	donor_gain	0.9900
4:127965607:G:GG	donor_gain	0.9900
4:127982937:A:AG	acceptor_gain	0.9900
4:127982938:G:GG	acceptor_gain	0.9900
4:127982938:GAT:G	acceptor_gain	0.9900
4:127984334:A:AG	acceptor_gain	0.9900
4:127984336:TAGAC:T	acceptor_loss	0.9900
4:127984337:AGACT:A	acceptor_loss	0.9900
4:127984338:GAC:G	acceptor_gain	0.9900
4:127984338:GACT:G	acceptor_gain	0.9900

AlphaMissense

3052 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:127983022:T:A	W23R	1.000
4:127983022:T:C	W23R	1.000
4:128011682:G:C	R151T	1.000
4:128011682:G:T	R151M	1.000
4:128011683:G:C	R151S	1.000
4:128011683:G:T	R151S	1.000
4:128030554:G:C	D375H	1.000
4:128030555:A:T	D375V	1.000
4:128030599:T:A	W390R	1.000
4:128030599:T:C	W390R	1.000
4:127982974:G:C	D7H	0.999
4:127982975:A:T	D7V	0.999
4:127983010:T:C	F19L	0.999
4:127983012:T:A	F19L	0.999
4:127983012:T:G	F19L	0.999
4:127983024:G:C	W23C	0.999
4:127983024:G:T	W23C	0.999
4:128008991:G:A	G117E	0.999
4:128009123:G:C	R125P	0.999
4:128009135:C:A	A129D	0.999
4:128017422:A:T	E177V	0.999
4:128017482:G:A	G197E	0.999
4:128017493:G:A	G201R	0.999
4:128017493:G:C	G201R	0.999
4:128017494:G:A	G201E	0.999
4:128017494:G:T	G201V	0.999
4:128017497:G:A	G202E	0.999
4:128020147:C:T	T226I	0.999
4:128020161:T:C	F231L	0.999
4:128020163:C:A	F231L	0.999

dbSNP variants (sampled 300 via entrez): RS1000024844 (4:128005920 C>T), RS1000035346 (4:127980424 C>G,T), RS1000063026 (4:127963768 A>G), RS1000085822 (4:127980747 C>G,T), RS1000114808 (4:128000096 G>A), RS1000190253 (4:128000378 G>A), RS1000197858 (4:127968196 C>G), RS1000290948 (4:127969408 A>G), RS1000292206 (4:128006622 G>A), RS1000294000 (4:127997470 A>AGTT), RS1000329411 (4:128037572 A>T), RS1000359186 (4:128010828 T>G), RS1000372368 (4:127994185 A>T), RS1000379084 (4:128010419 C>T), RS1000381792 (4:128037919 G>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:256730, MIM:610951

GenCC curated gene-disease

Mondo (3): neuronal ceroid lipofuscinosis (MONDO:0016295), neuronal ceroid lipofuscinosis 7 (MONDO:0012588), hereditary ataxia (MONDO:0100309)

Orphanet (5): Neuronal ceroid lipofuscinosis (Orphanet:216), OBSOLETE: Infantile neuronal ceroid lipofuscinosis (Orphanet:79263), OBSOLETE: Late infantile neuronal ceroid lipofuscinosis (Orphanet:168491), CLN7 disease (Orphanet:228366), Hereditary ataxia (Orphanet:183518)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C563989	Ceroid Lipofuscinosis, Neuronal, 7 (supp.)
C531684	Hereditary spinal ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6848982	ABHD18		0.00	0

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	decreases expression	1
K 7174	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	decreases expression, affects reaction	1
Atrazine	increases expression	1
Cisplatin	affects response to substance	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	increases methylation	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00337636	PHASE1	COMPLETED	Study of HuCNS-SC Cells in Patients With Infantile or Late Infantile Neuronal Ceroid Lipofuscinosis (NCL)
NCT01238315	PHASE1	WITHDRAWN	Safety and Efficacy Study of HuCNS-SC in Subjects With Neuronal Ceroid Lipofuscinosis
NCT04737460	PHASE1	ACTIVE_NOT_RECRUITING	Study for the Treatment for CLN7 Disease
NCT07582484	PHASE1/PHASE2	NOT_YET_RECRUITING	Gene Therapy Trial for CLN6 Batten Disease
NCT01873924	Not specified	RECRUITING	Clinical and Neuropsychological Investigations in Batten Disease
NCT01966757	Not specified	COMPLETED	Neuronal Ceroid Lipofuscinosis and Associated Sleep Abnormalities
NCT04613089	Not specified	RECRUITING	Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
NCT06844877	Not specified	RECRUITING	Italian NCL Registry: a Registry for NCL as an Integration Tool for Future Therapeutic Strategies
NCT01360164	PHASE1/PHASE2	UNKNOWN	Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Hereditary Ataxia
NCT00004306	Not specified	COMPLETED	Clinical and Molecular Correlations in Spinocerebellar Ataxia Type 10 (SCA10)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04750850	Not specified	COMPLETED	Core Stability Exercises and Hereditary Ataxia
NCT05160870	Not specified	UNKNOWN	Genotype-phenotype Correlation and Pathogenic Mechanism in Hereditary Ataxia
NCT05160883	Not specified	UNKNOWN	Neuroimaging Changes in Hereditary Ataxia
NCT06034886	Not specified	AVAILABLE	Expanded Access Protocol of Troriluzole in Patients With Spinocerebellar Ataxia (SCA)
NCT06152133	Not specified	COMPLETED	Telerehabilitation, Core Stability Exercises and Hereditary Ataxia (TRCore-ataxia)
NCT06267222	Not specified	ENROLLING_BY_INVITATION	Trans-spinal Electrical Stimulation in Individuals With Spinocerebellar Ataxia
NCT07092358	Not specified	RECRUITING	Hereditary Ataxia Research on Multi-Omics and Neuroclinical Insights in the Yangtze Delta
NCT07200505	Not specified	NOT_YET_RECRUITING	Telerehabilitation for Core Stability and Strength in Hereditary Ataxia