ABHD16A

Summary

ABHD16A (abhydrolase domain containing 16A, phospholipase, HGNC:13921) is a protein-coding gene on chromosome 6p21.33, encoding Phosphatidylserine lipase ABHD16A (O95870). Phosphatidylserine (PS) lipase that mediates the hydrolysis of phosphatidylserine to generate lysophosphatidylserine (LPS).

A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. The protein encoded by this gene is thought to be involved in some aspects of immunity. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 7920 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spastic paraplegia 86, autosomal recessive (Strong, GenCC)
• GWAS associations: 33
• Clinical variants (ClinVar): 119 total — 6 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021160

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13921
Approved symbol	ABHD16A
Name	abhydrolase domain containing 16A, phospholipase
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	NG26, D6S82E
Ensembl gene	ENSG00000204427
Ensembl biotype	protein_coding
OMIM	142620
Entrez	7920

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 21 protein_coding, 7 retained_intron, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000395952, ENST00000440843, ENST00000468037, ENST00000468205, ENST00000471644, ENST00000474007, ENST00000475742, ENST00000477016, ENST00000477462, ENST00000482224, ENST00000490209, ENST00000492084, ENST00000492899, ENST00000495769, ENST00000496579, ENST00000498420, ENST00000875896, ENST00000875897, ENST00000875898, ENST00000875899, ENST00000875900, ENST00000875901, ENST00000875902, ENST00000875903, ENST00000875904, ENST00000875905, ENST00000959092, ENST00000959093, ENST00000959094, ENST00000959095, ENST00000959096, ENST00000959097, ENST00000959098, ENST00000959099, ENST00000959100

RefSeq mRNA: 2 — MANE Select: NM_021160 NM_001177515, NM_021160

CCDS: CCDS4713, CCDS54988

Canonical transcript exons

ENST00000395952 — 20 exons

Exon	Start	End
ENSE00001887769	31686955	31687295
ENSE00001957166	31703150	31703324
ENSE00003475556	31702074	31702130
ENSE00003495905	31691804	31691918
ENSE00003505072	31689581	31689704
ENSE00003507902	31690539	31690602
ENSE00003529334	31688723	31688786
ENSE00003559380	31688041	31688103
ENSE00003563238	31687642	31687740
ENSE00003589619	31688249	31688305
ENSE00003598227	31696948	31697033
ENSE00003605515	31691579	31691680
ENSE00003631808	31701274	31701340
ENSE00003632251	31687824	31687900
ENSE00003640860	31689015	31689119
ENSE00003650007	31700942	31701028
ENSE00003663367	31693359	31693432
ENSE00003676890	31690078	31690127
ENSE00003690180	31687498	31687544
ENSE00003691397	31693027	31693149

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7242 / max 366.9890, expressed in 1808 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72787	20.2195	1807
72786	0.5047	196

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	98.19	gold quality
adenohypophysis	UBERON:0002196	98.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.84	gold quality
cerebellar hemisphere	UBERON:0002245	96.83	gold quality
cerebellum	UBERON:0002037	96.82	gold quality
cerebellar cortex	UBERON:0002129	96.82	gold quality
granulocyte	CL:0000094	96.46	gold quality
right lobe of thyroid gland	UBERON:0001119	96.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.37	gold quality
left testis	UBERON:0004533	96.34	gold quality
lower esophagus mucosa	UBERON:0035834	96.34	gold quality
right uterine tube	UBERON:0001302	96.33	gold quality
right testis	UBERON:0004534	96.32	gold quality
ganglionic eminence	UBERON:0004023	96.28	gold quality
spleen	UBERON:0002106	96.20	gold quality
left lobe of thyroid gland	UBERON:0001120	96.15	gold quality
blood	UBERON:0000178	96.02	gold quality
left uterine tube	UBERON:0001303	95.95	gold quality
thyroid gland	UBERON:0002046	95.87	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.77	gold quality
body of uterus	UBERON:0009853	95.75	gold quality
testis	UBERON:0000473	95.73	gold quality
prostate gland	UBERON:0002367	95.63	gold quality
mucosa of transverse colon	UBERON:0004991	95.59	gold quality
fallopian tube	UBERON:0003889	95.51	gold quality
transverse colon	UBERON:0001157	95.41	gold quality
fundus of stomach	UBERON:0001160	95.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.33	gold quality
right lobe of liver	UBERON:0001114	95.32	gold quality
endocervix	UBERON:0000458	95.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	32.97
E-ANND-3	yes	6.57
E-GEOD-99795	no	71.55
E-GEOD-124858	no	61.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting ABHD16A, 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-4531	99.99	69.70	3181
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-3928-3P	97.61	66.53	1096
HSA-MIR-6782-3P	97.60	67.75	931
HSA-MIR-596	97.48	63.13	469
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-4781-3P	95.78	65.66	572
HSA-MIR-6734-5P	95.70	65.56	950

Literature-anchored findings (GeneRIF, showing 6)

• Results suggest BAT2 -8671, BAT3 8854, and BAT5 22655, 9569 SNPs as well as BAT haplotypes (ATTGTG and ATCATG) might be associated with higher Kawasaki disease susceptibility and coronary artery aneurysm formation. (PMID:20626023)
• BAT5 is a genuine lipase with preference for long-chain unsaturated monoacylglycerols, and could in this capacity regulate glycerolipid metabolism in vivo as well. (PMID:25290914)
• ABHD16A is located on chromosome 6p21.33. It has 21 exons and four different transcripts, two of which encode proteins, while the other two encode LncRNAs. Its conformation revealed four transmembrane regions with 8 beta-strands and 6 alpha-helices as a typical a/b-hydrolase. [review] (PMID:29794032)
• Mapping the Neuroanatomy of ABHD16A, ABHD12, and Lysophosphatidylserines Provides New Insights into the Pathophysiology of the Human Neurological Disorder PHARC. (PMID:32462874)
• ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies. (PMID:34587489)
• A homozygous ABHD16A variant causes a complex hereditary spastic paraplegia with developmental delay, absent speech, and characteristic face. (PMID:34866177)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	abhd16a	ENSDARG00000078929
mus_musculus	Abhd16a	ENSMUSG00000007036
rattus_norvegicus	Abhd16a	ENSRNOG00000056637
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), ABHD16B (ENSG00000183260)

Protein

Protein identifiers

Phosphatidylserine lipase ABHD16A — O95870 (reviewed: O95870)

Alternative names: Alpha/beta hydrolase domain-containing protein 16A, HLA-B-associated transcript 5, Monoacylglycerol lipase ABHD16A, Protein G5

All UniProt accessions (5): O95870, A0A1U9X777, F2Z3G6, F2Z3H2, F2Z3Q3

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatidylserine (PS) lipase that mediates the hydrolysis of phosphatidylserine to generate lysophosphatidylserine (LPS). LPS constitutes a class of signaling lipids that regulates immunological and neurological processes. Has no activity towards diacylglycerol, triacylglycerol or lysophosphatidylserine lipase. Also has monoacylglycerol lipase activity, with preference for 1-(9Z,12Z-octadecadienoyl)-glycerol (1-LG) and 2-glyceryl-15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ(2)-G).

Subcellular location. Membrane.

Disease relevance. Spastic paraplegia 86, autosomal recessive (SPG86) [MIM:619735] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG86 is an autosomal recessive form associated with impaired intellectual development, poor or absent speech, and behavioral abnormalities. Brain imaging shows thin corpus callosum and white matter abnormalities. Rare patients may have seizures. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by beta-lactone-based lipid inhibitors, such as beta-lactone palmostatin-B.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O95870-1	1	yes
O95870-2	2

RefSeq proteins (2): NP_001170986, NP_066983* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR054518	ABHD16_N	Domain

Pfam: PF00561, PF22990

Catalyzed reactions (Rhea), 12 shown:

• 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:26132)
• 1-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+) (RHEA:38487)
• 2-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+) (RHEA:38491)
• 2-hexadecanoylglycerol + H2O = glycerol + hexadecanoate + H(+) (RHEA:39963)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1’-sn-glycerol) + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-(1’-sn-glycerol) + (9Z)-octadecenoate + H(+) (RHEA:40919)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-L-serine + (9Z)-octadecenoate + H(+) (RHEA:41752)
• 1-tetradecanoylglycerol + H2O = tetradecanoate + glycerol + H(+) (RHEA:44312)
• 1-heptadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoserine + H2O = 1-heptadecanoyl-sn-glycero-3-phosphoserine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:44500)
• 1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoserine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoserine + (9Z,12Z)-octadecadienoate + H(+) (RHEA:44516)
• 1-heptadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 1-heptadecanoyl-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) (RHEA:44520)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoglycerol + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoglycerol + (9Z)-octadecenoate + H(+) (RHEA:44524)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol) + (9Z)-octadecenoate + H(+) (RHEA:44528)

UniProt features (18 total): sequence variant 8, active site 3, transmembrane region 2, chain 1, sequence conflict 1, topological domain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95870-F1	89.90	0.78

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): 355 (charge relay system); 430 (charge relay system); 507 (charge relay system)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 192 (showing top): ATF_B, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GCM_GSPT1, PEREZ_TP63_TARGETS, GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, CREBP1_Q2, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TAL1ALPHAE47_01, CAGCTG_AP4_Q5, CREB_Q4, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, IRF7_01, GOBP_NEUTRAL_LIPID_CATABOLIC_PROCESS, GCM_NUMA1, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS

GO Biological Process (4): phosphatidylserine catabolic process (GO:0006660), monoacylglycerol catabolic process (GO:0052651), prostaglandin catabolic process (GO:1905344), lipid metabolic process (GO:0006629)

GO Molecular Function (4): glycerophospholipase activity (GO:0004620), monoacylglycerol lipase activity (GO:0047372), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (1): membrane (GO:0016020)

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
prostanoid catabolic process	1
primary metabolic process	1
phospholipase activity	1
lipase activity	1
carboxylic ester hydrolase activity	1
binding	1
catalytic activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABHD16A	ABHD12	Q8N2K0	852
ABHD16A	ZBTB12	Q9Y330	829
ABHD16A	LST1	O00453	761
ABHD16A	PRRC2A	P48634	741
ABHD16A	ABHD6	Q9BV23	690
ABHD16A	DDX39B	Q13838	667
ABHD16A	GPANK1	O95872	654
ABHD16A	ABHD3	Q8WU67	647
ABHD16A	HLA-B	P01889	622
ABHD16A	LY6G5C	Q5SRR4	615
ABHD16A	LTA	P01374	594
ABHD16A	U2AF2	P26368	590
ABHD16A	ABHD13	Q7L211	590
ABHD16A	ABHD12B	Q7Z5M8	577
ABHD16A	ABHD2	P08910	568

IntAct

239 interactions, top by confidence:

A	B	Type	Score
ABHD16A	DTX2	psi-mi:“MI:0915”(physical association)	0.780
ABHD16A	RETREG3	psi-mi:“MI:0915”(physical association)	0.780
RNF5	ABHD16A	psi-mi:“MI:0915”(physical association)	0.780
DTX2	ABHD16A	psi-mi:“MI:0915”(physical association)	0.780
RETREG3	ABHD16A	psi-mi:“MI:0915”(physical association)	0.780
ABHD16A	RNF5	psi-mi:“MI:0915”(physical association)	0.780
ABHD16A	TMEM147	psi-mi:“MI:0915”(physical association)	0.670
TBC1D9	ABHD16A	psi-mi:“MI:0914”(association)	0.640
TMEM143	ABHD16A	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	ABHD16A	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	POLE	psi-mi:“MI:0915”(physical association)	0.560
ITGAM	ABHD16A	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	GORAB	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	SPAG4	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	RHBDD2	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (112): ABHD16A (Two-hybrid), DTX2 (Two-hybrid), FAM134C (Two-hybrid), ABHD16A (Affinity Capture-RNA), ABHD16A (Affinity Capture-MS), IFITM1 (Two-hybrid), RNF5 (Two-hybrid), HM13 (Two-hybrid), TMEM147 (Two-hybrid), TMEM222 (Two-hybrid), DNAJC1 (Two-hybrid), GPRC5C (Two-hybrid), SPAG7 (Two-hybrid), SAFB (Two-hybrid), ATP5G3 (Two-hybrid)

ESM2 similar proteins: A1L134, A9ULG4, B1H1N7, B2RUP2, D3ZI76, D3ZUM2, F1MLB4, I3L5V6, O95870, P47823, P70295, Q13144, Q14DK4, Q16586, Q1HAQ0, Q1JPD2, Q1LWG4, Q27J81, Q2TBP5, Q3TFD2, Q4R8P0, Q5NVK5, Q5R6S0, Q64350, Q643R3, Q6MG55, Q6NUI2, Q6NVG1, Q6PBN5, Q6PDS3, Q6SZW1, Q6V7V2, Q70J99, Q7TN37, Q8CHW4, Q8N0W3, Q8N9W5, Q8NF37, Q8TE02, Q95K25

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

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	4
Uncertain significance	69
Likely benign	13
Benign	1

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1162195	NM_021160.3(ABHD16A):c.1370G>A (p.Arg457Gln)	Pathogenic
1162196	NM_021160.3(ABHD16A):c.340C>T (p.Arg114Ter)	Pathogenic
1341326	NM_021160.3(ABHD16A):c.835C>T (p.Gln279Ter)	Pathogenic
3246158	NC_000006.11:g.(?31631971)(31895135_?)del	Pathogenic
4292648	NM_021160.3(ABHD16A):c.1402C>T (p.Arg468Ter)	Pathogenic
4292694	NM_021160.3(ABHD16A):c.514C>T (p.Arg172Ter)	Pathogenic
1297464	NM_021160.3(ABHD16A):c.1456del (p.Tyr486fs)	Likely pathogenic
3338455	GRCh37/hg19 6p21.33(chr6:31630124-31657924)x1	Likely pathogenic
3363138	NM_021160.3(ABHD16A):c.1307+1G>A	Likely pathogenic
4682662	GRCh37/hg19 6p21.33(chr6:30944923-31867966)x1	Likely pathogenic

SpliceAI

2554 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31687492:G:C	donor_gain	1.0000
6:31687542:CCC:C	acceptor_gain	1.0000
6:31687543:CC:C	acceptor_gain	1.0000
6:31687543:CCC:C	acceptor_gain	1.0000
6:31687544:CC:C	acceptor_gain	1.0000
6:31687545:C:CC	acceptor_gain	1.0000
6:31687636:CCTTA:C	donor_loss	1.0000
6:31687637:CTTA:C	donor_loss	1.0000
6:31687637:CTTAC:C	donor_loss	1.0000
6:31687638:TTA:T	donor_loss	1.0000
6:31687639:TA:T	donor_loss	1.0000
6:31687639:TACC:T	donor_loss	1.0000
6:31687640:A:AC	donor_gain	1.0000
6:31687640:A:AT	donor_loss	1.0000
6:31687640:AC:A	donor_gain	1.0000
6:31687641:C:CC	donor_gain	1.0000
6:31687641:C:G	donor_loss	1.0000
6:31687641:CC:C	donor_gain	1.0000
6:31687641:CCCA:C	donor_gain	1.0000
6:31687645:CG:C	donor_gain	1.0000
6:31687736:TGAGG:T	acceptor_gain	1.0000
6:31687737:GAGG:G	acceptor_gain	1.0000
6:31687738:AGG:A	acceptor_gain	1.0000
6:31687739:GG:G	acceptor_gain	1.0000
6:31687741:C:CC	acceptor_gain	1.0000
6:31687746:C:CT	acceptor_gain	1.0000
6:31687747:A:T	acceptor_gain	1.0000
6:31687820:TCA:T	donor_loss	1.0000
6:31687821:CACC:C	donor_loss	1.0000
6:31687822:ACCTT:A	donor_gain	1.0000

AlphaMissense

3603 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31687260:G:C	H543Q	1.000
6:31687260:G:T	H543Q	1.000
6:31688267:T:A	D430V	1.000
6:31688268:C:G	D430H	1.000
6:31688275:T:A	R427S	1.000
6:31688275:T:G	R427S	1.000
6:31688276:C:A	R427I	1.000
6:31688276:C:G	R427T	1.000
6:31689061:A:C	F380L	1.000
6:31689061:A:T	F380L	1.000
6:31689063:A:G	F380L	1.000
6:31689602:A:G	W354R	1.000
6:31689602:A:T	W354R	1.000
6:31690090:A:C	F315L	1.000
6:31690090:A:T	F315L	1.000
6:31690092:A:G	F315L	1.000
6:31690102:A:C	N311K	1.000
6:31690102:A:T	N311K	1.000
6:31690107:A:G	W310R	1.000
6:31690107:A:T	W310R	1.000
6:31690573:A:C	F291L	1.000
6:31690573:A:T	F291L	1.000
6:31690575:A:G	F291L	1.000
6:31690582:A:C	N288K	1.000
6:31690582:A:T	N288K	1.000
6:31690586:C:A	G287V	1.000
6:31690587:C:A	G287W	1.000
6:31690587:C:G	G287R	1.000
6:31690587:C:T	G287R	1.000
6:31696996:G:C	F127L	1.000

dbSNP variants (sampled 300 via entrez): RS1000470101 (6:31688011 C>A), RS1000958518 (6:31693656 C>G), RS1001055964 (6:31701842 T>A), RS1001121901 (6:31700214 C>T), RS1001266566 (6:31700673 G>A), RS1001348710 (6:31694021 G>A), RS1001632506 (6:31697570 T>G), RS1001680178 (6:31692746 C>A,G,T), RS1001727819 (6:31705200 A>G), RS1001752234 (6:31693069 G>A,T), RS1001780258 (6:31704876 C>A,T), RS1002025752 (6:31698048 G>A), RS1002085157 (6:31689845 T>C,G), RS1002139009 (6:31689522 G>A,C,T), RS1003043450 (6:31697767 C>A,T)

Disease associations

OMIM: gene MIM:142620 | disease phenotypes: MIM:619735, MIM:618732

GenCC curated gene-disease

Disease	Classification	Inheritance
spastic paraplegia 86, autosomal recessive	Strong	Autosomal recessive

Mondo (4): complex hereditary spastic paraplegia (MONDO:0015150), spastic paraplegia 86, autosomal recessive (MONDO:0030673), neurodevelopmental disorder (MONDO:0700092), Poirier-Bienvenu neurodevelopmental syndrome (MONDO:0032889)

Orphanet (4): Complex hereditary spastic paraplegia (Orphanet:102013), Autosomal recessive spastic paraplegia type 86 (Orphanet:631085), Autosomal recessive complex spastic paraplegia (Orphanet:100981), Poirier-Bienvenu neurodevelopmental syndrome (Orphanet:689397)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001258	Spastic paraplegia
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001772	Talipes equinovalgus
HP:0001776	Bilateral talipes equinovarus
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002460	Distal muscle weakness
HP:0002540	Inability to walk
HP:0002650	Scoliosis
HP:0003487	Babinski sign
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0030891	Periventricular white matter hyperintensities
HP:0033725	Thin corpus callosum

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST001227_1	Systolic blood pressure	2.000000e-11
GCST001228_19	Diastolic blood pressure	3.000000e-11
GCST001238_6	Hypertension	1.000000e-10
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_224	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_281	Autism spectrum disorder or schizophrenia	5.000000e-09
GCST004521_45	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST004776_24	Systolic blood pressure	6.000000e-06
GCST004777_12	Diastolic blood pressure	4.000000e-06
GCST006021_39	Systolic blood pressure	3.000000e-06
GCST006258_32	Diastolic blood pressure	4.000000e-11
GCST008916_111	Asthma	2.000000e-14
GCST008916_114	Asthma	1.000000e-09
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16
GCST009391_1525	Metabolite levels	6.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0010418	triacylglycerol 52:6 measurement
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6168 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,186 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL175247	ORLISTAT	4	38,186

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

ChEMBL bioactivities

13 potent at pChembl≥5 of 16 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.52	IC50	30	nM	ORLISTAT
7.52	IC50	30	nM	CHEMBL4564841
7.50	IC50	32	nM	CHEMBL4564841
7.24	IC50	57	nM	PALMOSTATIN B
7.22	IC50	60	nM	CHEMBL5532498
7.05	IC50	90	nM	CHEMBL4525638
7.00	IC50	99	nM	PALMOSTATIN B
7.00	IC50	100	nM	PALMOSTATIN B
6.77	IC50	170	nM	ORLISTAT
6.70	IC50	200	nM	CHEMBL4525638
5.47	IC50	3400	nM	CHEMBL4585683
5.31	IC50	4900	nM	CHEMBL4591378

PubChem BioAssay actives

13 with measured affinity, of 55 total; 7 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Orlistat	409654: Inhibition of recombinant BAT5 transfected in HEK293T cells by SDS-PAGE using rhodamine-tagged FP probe	ic50	0.0300	uM
3-(4-fluorophenyl)-5-methoxy-1,3,4-oxadiazol-2-one	2084142: Inhibition of recombinant human ABHD16A expressed in HEK293T cells incubated for 1 hr by fluorescence based analysis	ic50	0.0300	uM
(3S,4S)-3-decyl-4-[2-(3,4-dimethoxyphenyl)ethyl]oxetan-2-one	1533316: Reversible inhibition of human ABHD16A expressed in HEK293 cells preincubated for 30 mins followed by 40 fold compound dilution and subsequent 1-LG substrate addition and measured at 30 mins time interval for 120 mins by fluorometric assay	ic50	0.0570	uM
5-methoxy-3-(3-nitrophenyl)-1,3,4-oxadiazol-2-one	2084142: Inhibition of recombinant human ABHD16A expressed in HEK293T cells incubated for 1 hr by fluorescence based analysis	ic50	0.0600	uM
(6Z)-6-(2-oxo-4-tridecyloxetan-3-ylidene)hexanamide	1533311: Inhibition of ABHD16A (unknown origin)	ic50	0.0900	uM
methyl (1R,4aS,10aR)-1,4a-dimethyl-6-(2-methyl-1,3-thiazol-4-yl)-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylate	1533315: Inhibition of human ABHD16A expressed in HEK293 cells preincubated for 30 mins followed by 1-LG substrate addition and measured after 90 to 120 mins by fluorometric assay	ic50	3.4000	uM
methyl (1R,4aS,10aR)-6-(2-cyano-1,3-thiazol-4-yl)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylate	1533315: Inhibition of human ABHD16A expressed in HEK293 cells preincubated for 30 mins followed by 1-LG substrate addition and measured after 90 to 120 mins by fluorometric assay	ic50	4.9000	uM

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	increases abundance, increases expression, affects cotreatment	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
1,6-bis(cyclohexyloximinocarbonyl)hexane	decreases activity	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
Bortezomib	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Orlistat	decreases activity	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1
Coumestrol	decreases expression	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Phthalic Acids	increases methylation	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2209087	Binding	Inhibition of BAT5 binding to FP-biotin in [12C][14N]-lysine, arginine and [13C6][15N2]-lysine, arginine labeled HEK293T cells at 20 uM after 1 hr by isotopic activity-based protein profiling-MudPIT assay	Discovery and optimization of sulfonyl acrylonitriles as selective, covalent inhibitors of protein phosphatase methylesterase-1. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice