ABHD16B

Summary

ABHD16B (abhydrolase domain containing 16B, HGNC:16128) is a protein-coding gene on chromosome 20q13.33, encoding ABHD16B (Q9H3Z7). Hydrolyzes the sn-1 position of glycerophospholipids with high specificity towards phosphatidylserine (PS), PS-PLA1 enzyme.

Predicted to enable monoacylglycerol lipase activity and phospholipase activity. Predicted to be involved in monoacylglycerol catabolic process and phosphatidylserine catabolic process. Located in nucleoplasm.

Source: NCBI Gene 140701 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 136 total — 12 pathogenic, 4 likely-pathogenic
• MANE Select transcript: NM_080622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16128
Approved symbol	ABHD16B
Name	abhydrolase domain containing 16B
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	dJ591C20.1
Ensembl gene	ENSG00000183260
Ensembl biotype	protein_coding
OMIM	620190
Entrez	140701

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000369916

RefSeq mRNA: 1 — MANE Select: NM_080622 NM_080622

CCDS: CCDS13539

Canonical transcript exons

ENST00000369916 — 1 exons

Exon	Start	End
ENSE00001451246	63861498	63862988

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 75.50.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	75.50	gold quality
left testis	UBERON:0004533	74.81	gold quality
testis	UBERON:0000473	69.54	gold quality
parotid gland	UBERON:0001831	64.09	gold quality
tendon of biceps brachii	UBERON:0008188	62.56	gold quality
cartilage tissue	UBERON:0002418	61.73	gold quality
mucosa of transverse colon	UBERON:0004991	60.28	gold quality
myocardium	UBERON:0002349	56.60	gold quality
decidua	UBERON:0002450	52.31	gold quality
medial globus pallidus	UBERON:0002477	51.96	gold quality
trabecular bone tissue	UBERON:0002483	51.25	gold quality
ventricular zone	UBERON:0003053	50.49	gold quality
globus pallidus	UBERON:0001875	49.36	gold quality
vastus lateralis	UBERON:0001379	48.89	gold quality
quadriceps femoris	UBERON:0001377	48.69	gold quality
Brodmann (1909) area 46	UBERON:0006483	48.36	gold quality
amniotic fluid	UBERON:0000173	46.80	gold quality
cortical plate	UBERON:0005343	46.73	gold quality
ganglionic eminence	UBERON:0004023	46.01	gold quality
adult organism	UBERON:0007023	45.69	gold quality
middle temporal gyrus	UBERON:0002771	45.49	gold quality
buccal mucosa cell	CL:0002336	45.04	gold quality
gingiva	UBERON:0001828	43.97	gold quality
blood	UBERON:0000178	43.79	gold quality
skeletal muscle tissue	UBERON:0001134	43.64	gold quality
substantia nigra pars compacta	UBERON:0001965	43.51	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
heart right ventricle	UBERON:0002080	41.91	gold quality
colonic epithelium	UBERON:0000397	41.43	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Molecular insights on PS-PLA1 lipase activity of human ABHD16B. (PMID:36841071)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	abhd12	ENSDARG00000071004
mus_musculus	Abhd16b	ENSMUSG00000055882
rattus_norvegicus	Abhd16b	ENSRNOG00000015067
drosophila_melanogaster	CG1309	FBGN0035519
caenorhabditis_elegans		WBGENE00008497
caenorhabditis_elegans		WBGENE00008498
caenorhabditis_elegans		WBGENE00018131

Paralogs (7): ABHD12 (ENSG00000100997), ABHD17B (ENSG00000107362), ABHD17A (ENSG00000129968), ABHD12B (ENSG00000131969), ABHD17C (ENSG00000136379), ABHD13 (ENSG00000139826), ABHD16A (ENSG00000204427)

Protein

Protein identifiers

ABHD16B — Q9H3Z7 (reviewed: Q9H3Z7)

Alternative names: Alpha/beta hydrolase domain-containing protein 16B

All UniProt accessions (1): Q9H3Z7

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes the sn-1 position of glycerophospholipids with high specificity towards phosphatidylserine (PS), PS-PLA1 enzyme. Also hydrolyzes the acyl chain of glycerolipids with a preference for the monoacylglycerol (MAG) 1-acylglycerol, MAG lipase. Plays a regulatory role in cellular lipid homeostasis by modulating genes involved in neutral lipid degradation and in phospholipid synthesis and composition.

Similarity. Belongs to the AB hydrolase superfamily. ABHD16 family.

RefSeq proteins (1): NP_542189* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF00561

Catalyzed reactions (Rhea), 3 shown:

• a 1-acylglycerol + H2O = glycerol + a fatty acid + H(+) (RHEA:34019)
• 1-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+) (RHEA:38487)
• a 1,2-diacyl-sn-glycero-3-phospho-L-serine + H2O = a 2-acyl-sn-glycero-3-phospho-L-serine + a fatty acid + H(+) (RHEA:42212)

UniProt features (6 total): active site 3, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3Z7-F1	86.64	0.72

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): 247 (charge relay system); 322 (charge relay system); 418 (charge relay system)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_NEUTRAL_LIPID_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_CATABOLIC_PROCESS, GOBP_NEUTRAL_LIPID_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_CATABOLIC_PROCESS, GOBP_PHOSPHATIDYLSERINE_METABOLIC_PROCESS, GOBP_LIPID_CATABOLIC_PROCESS, GOBP_PHOSPHOLIPID_CATABOLIC_PROCESS, GOBP_MODIFIED_AMINO_ACID_METABOLIC_PROCESS

GO Biological Process (3): phosphatidylserine catabolic process (GO:0006660), monoacylglycerol catabolic process (GO:0052651), lipid metabolic process (GO:0006629)

GO Molecular Function (3): glycerophospholipase activity (GO:0004620), monoacylglycerol lipase activity (GO:0047372), hydrolase activity (GO:0016787)

GO Cellular Component (1): nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatidylserine metabolic process	1
modified amino acid catabolic process	1
glycerophospholipid catabolic process	1
monoacylglycerol metabolic process	1
acylglycerol catabolic process	1
primary metabolic process	1
phospholipase activity	1
lipase activity	1
carboxylic ester hydrolase activity	1
catalytic activity	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

420 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABHD16B	ABHD12B	Q7Z5M8	676
ABHD16B	ABHD1	Q96SE0	629
ABHD16B	ABHD14A	Q9BUJ0	620
ABHD16B	ABHD13	Q7L211	600
ABHD16B	ABHD8	Q96I13	595
ABHD16B	ABHD15	Q6UXT9	571
ABHD16B	ABHD10	Q9NUJ1	553
ABHD16B	ABHD2	P08910	548
ABHD16B	ABHD18	Q0P651	533
ABHD16B	ABHD11	Q8NFV4	530
ABHD16B	FNDC11	Q9BVV2	517
ABHD16B	ABHD14B	Q96IU4	493
ABHD16B	ABHD12	Q8N2K0	479
ABHD16B	ABHD6	Q9BV23	477
ABHD16B	ABHD3	Q8WU67	474

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ABHD16B	HSPD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): ABHD16B (Affinity Capture-MS), ABHD16B (Affinity Capture-MS), ABHD16B (Negative Genetic), HSPD1 (Affinity Capture-MS), MFHAS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A5F8AH41, A0AVI4, A7S641, O75843, P10937, P25235, P40935, P70345, Q06AU9, Q08DJ7, Q08DK0, Q0IJ33, Q14AI0, Q28647, Q28CM7, Q3V3N7, Q4R7D0, Q503C8, Q5FVF4, Q5R5N9, Q5RDY9, Q5XIL6, Q5ZI25, Q68F70, Q6IR55, Q6NWH5, Q6PD82, Q74ZJ1, Q7KNA0, Q7QIL2, Q80YU0, Q8CHY3, Q8CIM8, Q8IV36, Q8K304, Q8MRQ4, Q8NFJ9, Q8R1F6, Q8R307, Q8WW52

Diamond homologs: O95870, P41879, Q1JPD2, Q4R8P0, Q5R6S0, Q5XIL6, Q6MG55, Q80YU0, Q9H3Z7, Q9Z1Q2, A5PKD9, B5DFK7, Q5ZJX1, Q6PCB6, Q7ZVZ7, Q8VCV1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	4
Uncertain significance	118
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
1340670	GRCh37/hg19 20q13.33(chr20:61775756-62915555)x1	Pathogenic
148310	GRCh38/hg38 20q13.33(chr20:63153963-64277321)x1	Pathogenic
148973	GRCh38/hg38 20q13.2-13.33(chr20:56198032-64277321)x3	Pathogenic
1526699	GRCh37/hg19 20q13.33(chr20:61619222-62915555)	Pathogenic
153207	GRCh38/hg38 20q13.33(chr20:62663307-64284202)x1	Pathogenic
153305	GRCh38/hg38 20q13.33(chr20:62582073-64284202)x1	Pathogenic
160985	GRCh38/hg38 20q13.33(chr20:63199020-64277321)x3	Pathogenic
253445	GRCh37/hg19 20q13.33(chr20:61827144-62907526)x1	Pathogenic
4075881	GRCh37/hg19 20q13.33(chr20:61737575-62915555)x1	Pathogenic
442701	GRCh37/hg19 20q13.33(chr20:61884113-62915555)x1	Pathogenic
58975	GRCh38/hg38 20q13.33(chr20:62545370-64241486)x1	Pathogenic
816137	GRCh37/hg19 20q13.33(chr20:61152321-62915555)x1	Pathogenic
1326335	GRCh37/hg19 20q13.33(chr20:61273854-62907579)	Likely pathogenic
1326336	GRCh37/hg19 20q13.33(chr20:61038552-62907579)	Likely pathogenic
146197	GRCh38/hg38 20q13.33(chr20:63199020-64277321)x1	Likely pathogenic
441724	GRCh37/hg19 20q13.2-13.33(chr20:51542616-62915555)x3	Likely pathogenic

SpliceAI

35 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63862220:TC:T	donor_gain	0.5400
20:63862266:G:GA	donor_gain	0.4400
20:63862217:TGGTC:T	donor_gain	0.4300
20:63862218:GGTCG:G	donor_gain	0.4300
20:63862504:G:GT	donor_gain	0.4200
20:63862224:G:GG	donor_gain	0.4100
20:63862223:A:AG	donor_gain	0.3800
20:63862265:T:TA	donor_gain	0.3800
20:63862515:C:A	donor_gain	0.3800
20:63862678:G:GT	donor_gain	0.3500
20:63862386:C:A	donor_gain	0.3200
20:63862551:TG:T	donor_gain	0.3000
20:63862387:A:AG	donor_gain	0.2900
20:63862553:AC:A	donor_gain	0.2900
20:63862508:ACGT:A	donor_gain	0.2800
20:63862511:T:A	donor_gain	0.2800
20:63862327:C:G	donor_gain	0.2700
20:63862385:T:TA	donor_gain	0.2700
20:63862777:G:GT	donor_gain	0.2700
20:63862210:G:GT	donor_gain	0.2600
20:63862512:G:GA	donor_gain	0.2500
20:63862714:G:GT	donor_gain	0.2500
20:63862773:C:T	donor_gain	0.2500
20:63862280:C:A	donor_gain	0.2400
20:63862723:C:G	donor_gain	0.2400
20:63862229:C:T	donor_gain	0.2300
20:63862768:G:GT	donor_gain	0.2300
20:63862771:G:GT	donor_gain	0.2200
20:63862077:C:T	donor_gain	0.2100
20:63862570:GGCAA:G	donor_gain	0.2100

AlphaMissense

2989 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63862159:T:C	F207L	0.969
20:63862161:C:A	F207L	0.969
20:63862161:C:G	F207L	0.969
20:63862144:T:A	W202R	0.966
20:63862144:T:C	W202R	0.966
20:63862354:T:C	F272L	0.961
20:63862356:C:A	F272L	0.961
20:63862356:C:G	F272L	0.961
20:63862087:T:C	F183L	0.959
20:63862089:C:A	F183L	0.959
20:63862089:C:G	F183L	0.959
20:63862804:T:C	F422L	0.950
20:63862806:C:A	F422L	0.950
20:63862806:C:G	F422L	0.950
20:63862291:T:C	F251L	0.948
20:63862293:C:A	F251L	0.948
20:63862293:C:G	F251L	0.948
20:63862603:C:A	R355S	0.934
20:63862606:T:G	Y356D	0.934
20:63862861:T:C	F441L	0.932
20:63862863:C:A	F441L	0.932
20:63862863:C:G	F441L	0.932
20:63862246:T:C	F236L	0.923
20:63862248:C:A	F236L	0.923
20:63862248:C:G	F236L	0.923
20:63862146:G:C	W202C	0.921
20:63862146:G:T	W202C	0.921
20:63862495:C:A	R319S	0.918
20:63862927:T:C	F463L	0.914
20:63862929:T:A	F463L	0.914

dbSNP variants (sampled 300 via entrez): RS1000397742 (20:63862719 G>A,C), RS1000755296 (20:63861254 A>G), RS1001026041 (20:63860737 C>G), RS1001167842 (20:63862023 C>G,T), RS1001359164 (20:63863067 C>G,T), RS1002609843 (20:63860386 G>A), RS1002979166 (20:63861002 G>A), RS1003245802 (20:63860753 G>A,T), RS1003335658 (20:63862613 T>G), RS1003716673 (20:63859834 C>A), RS1004660534 (20:63861570 G>A,C), RS1005833194 (20:63861609 C>T), RS1006094734 (20:63861347 G>T), RS1006294753 (20:63860742 A>T), RS1006327432 (20:63860546 T>C)

Disease associations

OMIM: gene MIM:620190 | disease phenotypes: MIM:121200, MIM:613720, MIM:616409, MIM:600513, MIM:256730

GenCC curated gene-disease

Mondo (6): seizures, benign familial neonatal, 1 (MONDO:0007365), developmental and epileptic encephalopathy, 7 (MONDO:0013387), developmental and epileptic encephalopathy, 33 (MONDO:0014625), developmental and epileptic encephalopathy (MONDO:0100620), familial sleep-related hypermotor epilepsy (MONDO:0000030), neuronal ceroid lipofuscinosis (MONDO:0016295)

Orphanet (6): Self-limited neonatal epilepsy (Orphanet:1949), KCNQ2-related developmental and epileptic encephalopathy (Orphanet:439218), Non-specific early-onset epileptic encephalopathy (Orphanet:442835), Neuronal ceroid lipofuscinosis (Orphanet:216), OBSOLETE: Infantile neuronal ceroid lipofuscinosis (Orphanet:79263), Sleep-related hypermotor epilepsy (Orphanet:98784)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001942_22	Prostate cancer	4.000000e-16
GCST009391_1569	Metabolite levels	5.000000e-06
GCST011495_4	Abdominal aortic aneurysm	8.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010516	orotic acid measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C579932	Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (supp.)
C567743	Epilepsy, Benign Neonatal, 1, And-Or Myokymia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
aminomethylphosphonic acid (AMPA)	decreases expression	1
dicrotophos	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, increases expression	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
2,4-Dichlorophenoxyacetic Acid	decreases expression	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
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
NCT03876444	PHASE2/PHASE3	UNKNOWN	Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05538936	Not specified	COMPLETED	The Effect of Spa and Massage on Babies on Colic Symptoms
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06266234	Not specified	RECRUITING	Characterization by Automated System on Infantile Spasmes
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07413211	Not specified	RECRUITING	Genetic Developmental and Epileptic Encephalopathy Natural History Study for Clinical Trial Readiness
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).
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