ACSM3

Summary

ACSM3 (acyl-CoA synthetase medium chain family member 3, HGNC:10522) is a protein-coding gene on chromosome 16p12.3, encoding Acyl-coenzyme A synthetase ACSM3, mitochondrial (Q53FZ2). Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism.

Enables medium-chain fatty acid-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. Implicated in IgA glomerulonephritis. Biomarker of ulcerative colitis.

Source: NCBI Gene 6296 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 184 total — 6 pathogenic, 1 likely-pathogenic
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_005622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10522
Approved symbol	ACSM3
Name	acyl-CoA synthetase medium chain family member 3
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	SA
Ensembl gene	ENSG00000005187
Ensembl biotype	protein_coding
OMIM	145505
Entrez	6296

Gene structure

Transcript identifiers

Ensembl transcripts: 54 — 48 protein_coding, 5 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000289416, ENST00000440284, ENST00000501740, ENST00000561499, ENST00000561584, ENST00000561795, ENST00000562251, ENST00000563914, ENST00000564701, ENST00000567006, ENST00000567387, ENST00000567711, ENST00000568235, ENST00000569141, ENST00000614721, ENST00000887872, ENST00000887873, ENST00000887874, ENST00000887875, ENST00000887876, ENST00000887877, ENST00000887878, ENST00000887879, ENST00000887880, ENST00000887881, ENST00000887882, ENST00000887883, ENST00000887884, ENST00000887885, ENST00000887886, ENST00000966442, ENST00000966443, ENST00000966444, ENST00000966445, ENST00000966446, ENST00000966447, ENST00000966448, ENST00000966449, ENST00000966450, ENST00000966451, ENST00000966452, ENST00000966453, ENST00000966454, ENST00000966455, ENST00000966456, ENST00000966457, ENST00000966458, ENST00000966459, ENST00000966460, ENST00000966461, ENST00000966462, ENST00000966463, ENST00000966464, ENST00000966465

RefSeq mRNA: 2 — MANE Select: NM_005622 NM_005622, NM_202000

CCDS: CCDS10589, CCDS45435

Canonical transcript exons

ENST00000289416 — 14 exons

Exon	Start	End
ENSE00001141895	20781708	20781787
ENSE00001141902	20780974	20781130
ENSE00001141911	20780714	20780857
ENSE00001141919	20777373	20777580
ENSE00001141927	20775839	20776049
ENSE00001141946	20769984	20770253
ENSE00001859826	20796886	20797581
ENSE00002620983	20764014	20764125
ENSE00003507674	20792002	20792129
ENSE00003542370	20786078	20786158
ENSE00003551209	20792236	20792335
ENSE00003565381	20784984	20785107
ENSE00003576036	20790587	20790688
ENSE00003627288	20796370	20796489

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 98.79.

FANTOM5 (CAGE): breadth broad, TPM avg 4.6981 / max 200.2936, expressed in 717 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153067	2.6539	513
153063	0.9031	213
153068	0.6070	121
153062	0.3085	99
153065	0.1813	88
153066	0.0443	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	98.79	gold quality
right ovary	UBERON:0002118	98.66	gold quality
right lobe of liver	UBERON:0001114	96.68	gold quality
adrenal tissue	UBERON:0018303	96.65	gold quality
left uterine tube	UBERON:0001303	96.36	gold quality
body of pancreas	UBERON:0001150	96.05	gold quality
right uterine tube	UBERON:0001302	94.12	gold quality
ovary	UBERON:0000992	93.25	gold quality
mucosa of transverse colon	UBERON:0004991	93.25	gold quality
body of uterus	UBERON:0009853	93.22	gold quality
adult mammalian kidney	UBERON:0000082	92.87	gold quality
liver	UBERON:0002107	92.85	gold quality
body of stomach	UBERON:0001161	92.17	gold quality
rectum	UBERON:0001052	91.62	gold quality
mucosa of stomach	UBERON:0001199	91.57	gold quality
left testis	UBERON:0004533	89.93	gold quality
pancreas	UBERON:0001264	89.87	gold quality
kidney	UBERON:0002113	89.76	gold quality
stomach	UBERON:0000945	89.51	gold quality
right testis	UBERON:0004534	89.02	gold quality
metanephros cortex	UBERON:0010533	88.28	gold quality
ectocervix	UBERON:0012249	88.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.77	gold quality
endocervix	UBERON:0000458	87.67	gold quality
testis	UBERON:0000473	87.37	gold quality
transverse colon	UBERON:0001157	87.32	gold quality
right lung	UBERON:0002167	87.20	gold quality
apex of heart	UBERON:0002098	86.13	gold quality
nephron tubule	UBERON:0001231	85.91	gold quality
cortex of kidney	UBERON:0001225	85.51	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	431.05
E-HCAD-4	yes	51.53
E-MTAB-10287	yes	16.50
E-ANND-3	yes	7.66
E-CURD-122	yes	5.69
E-MTAB-9801	no	3.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting ACSM3, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-6776-3P	98.38	66.34	655
HSA-MIR-144-5P	97.66	69.90	531
HSA-MIR-203A-5P	96.33	65.03	714
HSA-MIR-6821-3P	95.21	66.79	578
HSA-MIR-5186	94.63	66.76	627

Literature-anchored findings (GeneRIF, showing 11)

• SA gene polymorphism may be associated with the renal prognosis of immunoglobulin A nephropathy through its effect on blood pressure. Sensitivity to this gene polymorphism increases in patients with renal injury. (PMID:12484505)
• variation in SAH has a role in predisposition to overweight in hypertensives. (PMID:14567496)
• confirms recent evidence that the SAH locus is associated with obesity-related hypertension (PMID:17278971)
• family-based analyses of SA hypertension-associated homolog (SAH) gene variants did not reveal population stratification supporting an association of hypertension and gene variants (PMID:18192838)
• We conclude that, in spite of its renal expression,1-3 the human SAH gene is unlikely to have an important role in renal sodium handling. (PMID:18519841)
• SA hypertension-associated homolog(SAH) gene polymorphisms are associated with non-high-density lipoprotein cholesterol in postmenopausal women (PMID:19108963)
• left ventricular mass index and mean wall thickness , two phenotypes that are jointly influenced by blood pressure and obesity, might be related to variation in the human SAH gene (PMID:19262474)
• Reduced ACSM3 is associated with impaired butyrate oxidation in ulcerative colitis. (PMID:21987487)
• Our data provide evidence for a differential expression and regulation of the ACSM3 gene in hepatocellular carcinoma (PMID:28390038)
• ACSM3 suppresses the pathogenesis of high-grade serous ovarian carcinoma via promoting AMPK activity. (PMID:35124784)
• Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Is Regulated by Insulin Like Growth Factor 2 mRNA Binding Protein 3 (IGF2BP3) and Inhibits Proliferation, Motility and Stem Cell Properties of Breast Invasive Carcinoma. (PMID:37625834)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	acsm3	ENSDARG00000004880
mus_musculus	Acsm3	ENSMUSG00000030935
rattus_norvegicus	Acsm3	ENSRNOG00000032246
caenorhabditis_elegans		WBGENE00009221
caenorhabditis_elegans		WBGENE00018488

Paralogs (13): ACSM2B (ENSG00000066813), AACS (ENSG00000081760), ACSS3 (ENSG00000111058), ACSS2 (ENSG00000131069), ACSS1 (ENSG00000154930), AASDH (ENSG00000157426), ACSM1 (ENSG00000166743), ACSF2 (ENSG00000167107), ACSM6 (ENSG00000173124), ACSF3 (ENSG00000176715), ACSM5 (ENSG00000183549), ACSM2A (ENSG00000183747), ACSM4 (ENSG00000215009)

Protein

Protein identifiers

Acyl-coenzyme A synthetase ACSM3, mitochondrial — Q53FZ2 (reviewed: Q53FZ2)

Alternative names: Acyl-CoA synthetase medium-chain family member 3, Butyrate–CoA ligase 3, Butyryl-coenzyme A synthetase 3, Middle-chain acyl-CoA synthetase 3, Propionate–CoA ligase, Protein SA homolog

All UniProt accessions (8): Q53FZ2, H3BR33, H3BSM0, H3BT38, H3BTG0, H3BUF2, H3BV29, H3BVD5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism. Capable of activating medium-chain fatty acids with a preference for isobutyrate among fatty acids with 2-6 carbon atoms.

Subcellular location. Mitochondrion. Mitochondrion matrix.

Similarity. Belongs to the ATP-dependent AMP-binding enzyme family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q53FZ2-1	1	yes
Q53FZ2-2	2

RefSeq proteins (2): NP_005613, NP_973729 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000873	AMP-dep_synth/lig_dom	Domain
IPR020845	AMP-binding_CS	Conserved_site
IPR025110	AMP-bd_C	Domain
IPR042099	ANL_N_sf	Homologous_superfamily
IPR045851	AMP-b_sf	Homologous_superfamily
IPR051087	Mitochondrial_ACSM	Family

Pfam: PF00501, PF13193

Catalyzed reactions (Rhea), 6 shown:

• propanoate + ATP + CoA = propanoyl-CoA + AMP + diphosphate (RHEA:20373)
• octanoate + ATP + CoA = octanoyl-CoA + AMP + diphosphate (RHEA:33631)
• butanoate + ATP + CoA = butanoyl-CoA + AMP + diphosphate (RHEA:46172)
• 2-methylpropanoate + ATP + CoA = 2-methylpropanoyl-CoA + AMP + diphosphate (RHEA:46176)
• 2-methylbutanoate + ATP + CoA = 2-methylbutanoyl-CoA + AMP + diphosphate (RHEA:46180)
• a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate (RHEA:48340)

UniProt features (22 total): sequence conflict 6, binding site 5, sequence variant 4, modified residue 3, splice variant 2, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53FZ2-F1	90.12	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.

Ligand- & substrate-binding residues (5): 235–243; 374–379; 461; 476; 572

Post-translational modifications (3): 73, 106, 157

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-77352	Beta oxidation of butanoyl-CoA to acetyl-CoA
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-77286	mitochondrial fatty acid beta-oxidation of saturated fatty acids
R-HSA-77289	Mitochondrial Fatty Acid Beta-Oxidation
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 163 (showing top): GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_STEROL_HOMEOSTASIS, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_16HR_UP, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_LIPID_HOMEOSTASIS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP

GO Biological Process (6): fatty acid biosynthetic process (GO:0006633), acyl-CoA metabolic process (GO:0006637), regulation of blood pressure (GO:0008217), cholesterol homeostasis (GO:0042632), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (14): fatty-acyl-CoA synthase activity (GO:0004321), ATP binding (GO:0005524), fatty acid ligase activity (GO:0015645), propionate CoA-transferase activity (GO:0018729), medium-chain fatty acid-CoA ligase activity (GO:0031956), 2-methylbutanoate-CoA ligase activity (GO:0043759), metal ion binding (GO:0046872), propionate-CoA ligase activity (GO:0050218), nucleotide binding (GO:0000166), protein binding (GO:0005515), CoA-ligase activity (GO:0016405), ligase activity (GO:0016874), ligase activity, forming carbon-sulfur bonds (GO:0016877), acid-thiol ligase activity (GO:0016878)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
mitochondrial fatty acid beta-oxidation of saturated fatty acids	1
Metabolism	1
Mitochondrial Fatty Acid Beta-Oxidation	1
Fatty acid metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acid-thiol ligase activity	2
short-chain fatty acid-CoA ligase activity	2
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
nucleoside phosphate metabolic process	1
sulfur compound metabolic process	1
purine-containing compound metabolic process	1
blood circulation	1
regulation of biological quality	1
sterol homeostasis	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ATP-dependent activity	1
CoA-transferase activity	1
fatty acid-CoA ligase activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
ligase activity	1
ligase activity, forming carbon-sulfur bonds	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

2049 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACSM3	EHHADH	Q08426	642
ACSM3	SLC7A13	Q8TCU3	538
ACSM3	ACADS	P16219	481
ACSM3	SLC14A2	Q15849	480
ACSM3	ACADL	P28330	464
ACSM3	AASDH	Q4L235	455
ACSM3	SPAG8	Q99932	437
ACSM3	ERI2	A8K979	424
ACSM3	ACOT8	O14734	409
ACSM3	ADD3	Q9UEY8	409
ACSM3	ATP1A1	P05023	398
ACSM3	ACOX2	Q99424	391
ACSM3	CPT2	P23786	388
ACSM3	ACOT4	Q8N9L9	383
ACSM3	ECI1	P42126	377

IntAct

9 interactions, top by confidence:

A	B	Type	Score
SPSB2	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
SPSB4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
ACSM3	NUDT19	psi-mi:“MI:0914”(association)	0.350
MRPS24	VWA8	psi-mi:“MI:0914”(association)	0.350
SPSB4	BTAF1	psi-mi:“MI:0914”(association)	0.350
VCAM1		psi-mi:“MI:0914”(association)	0.350

BioGRID (19): ACSM3 (Biochemical Activity), MIPEP (Affinity Capture-MS), ACSM3 (Affinity Capture-MS), ARMC8 (Affinity Capture-MS), LRP4 (Affinity Capture-MS), NUDT19 (Affinity Capture-MS), CLUH (Affinity Capture-MS), ACSM3 (Affinity Capture-MS), ACSM3 (Affinity Capture-MS), ACSM3 (Affinity Capture-MS), ACSM3 (Proximity Label-MS), ACSM3 (Affinity Capture-MS), ACSM3 (Negative Genetic), ACSM3 (Affinity Capture-MS), ACSM3 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A4IHY0, H9A1V3, M4IRL9, O70490, P0C7M7, P39062, Q08AH1, Q08AH3, Q0P4F7, Q17QJ1, Q3TMV7, Q3UNX5, Q3URE1, Q499N5, Q4G176, Q4R3Y4, Q4R4Z9, Q4R510, Q53FZ2, Q58DN7, Q5E9H9, Q5EA45, Q5I0K5, Q5R9G9, Q5RDY4, Q5REV5, Q5REX5, Q67Y55, Q68CK6, Q6AYT9, Q6GLK6, Q6P1M0, Q6P461, Q6PE15, Q6SKG1, Q7T0X7, Q7TN78, Q80W40, Q84P17, Q8K0L3

Diamond homologs: A0A0H2ZF83, A0A0H2ZGB9, A8NF97, A9W5V0, B7KPN8, G3J456, M4IQQ5, M4ISH2, O07899, O53521, O60011, P0C7M7, P10378, P38135, P39002, P40871, P71716, P80436, P86831, P86832, P9WEY3, P9WEZ0, Q01574, Q08AH1, Q08AH3, Q1IAK8, Q21LV0, Q2G512, Q2KHW5, Q53FZ2, Q5P603, Q5REV5, Q5SKN9, Q5ZKR7, Q68CK6, Q6SKG1, Q6ZAC1, Q7TYX8, Q7X279, Q84HC5

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ACSM3	“down-regulates quantity”	butyrate	“chemical modification”
ACSM3	“down-regulates quantity”	ATP(4-)	“chemical modification”
ACSM3	“up-regulates quantity”	butyryl-CoA(4-)	“chemical modification”
ACSM3	“up-regulates quantity”	AMP	“chemical modification”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — GBM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	141
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1333095	NM_017736.5(THUMPD1):c.495dup (p.Ser166fs)	Pathogenic
1333097	NM_017736.5(THUMPD1):c.341T>G (p.Leu114Ter)	Pathogenic
1333098	NM_017736.5(THUMPD1):c.303_306del (p.Glu102fs)	Pathogenic
1333099	NM_017736.5(THUMPD1):c.469C>T (p.Arg157Ter)	Pathogenic
1333100	NM_017736.5(THUMPD1):c.490C>T (p.Pro164Ser)	Pathogenic
1333102	NM_017736.5(THUMPD1):c.634dup (p.Glu212fs)	Pathogenic
1333101	NM_017736.5(THUMPD1):c.771GTT[1] (p.Leu258del)	Likely pathogenic

SpliceAI

5330 predictions. Top by Δscore:

Variant	Effect	Δscore
16:20623571:ACCTG:A	acceptor_loss	1.0000
16:20623577:T:C	acceptor_gain	1.0000
16:20623577:T:TC	acceptor_gain	1.0000
16:20624092:TCACC:T	donor_loss	1.0000
16:20624094:ACC:A	donor_loss	1.0000
16:20624094:ACCTT:A	donor_gain	1.0000
16:20624095:C:CG	donor_loss	1.0000
16:20624095:CCTT:C	donor_gain	1.0000
16:20624095:CCTTC:C	donor_gain	1.0000
16:20624098:T:A	donor_gain	1.0000
16:20624217:T:A	acceptor_loss	1.0000
16:20627313:CACC:C	acceptor_gain	1.0000
16:20627315:CC:C	acceptor_gain	1.0000
16:20627316:CC:C	acceptor_gain	1.0000
16:20627316:CCT:C	acceptor_loss	1.0000
16:20627317:C:A	acceptor_loss	1.0000
16:20627317:C:CC	acceptor_gain	1.0000
16:20627318:T:C	acceptor_loss	1.0000
16:20661874:C:CC	acceptor_gain	1.0000
16:20682254:A:AC	donor_gain	1.0000
16:20682255:C:CC	donor_gain	1.0000
16:20682259:A:C	donor_gain	1.0000
16:20737282:TATTC:T	acceptor_gain	1.0000
16:20737284:TTC:T	acceptor_gain	1.0000
16:20737284:TTCC:T	acceptor_loss	1.0000
16:20737288:T:A	acceptor_loss	1.0000
16:20737703:CATA:C	donor_loss	1.0000
16:20737705:TA:T	donor_loss	1.0000
16:20737706:A:AG	donor_loss	1.0000
16:20737707:CCT:C	donor_loss	1.0000

AlphaMissense

3840 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:20781008:T:A	W273R	0.995
16:20781008:T:C	W273R	0.995
16:20781065:T:A	W292R	0.995
16:20781065:T:C	W292R	0.995
16:20785054:T:A	W364R	0.993
16:20785054:T:C	W364R	0.993
16:20785103:A:T	E380V	0.993
16:20776044:G:C	R142P	0.992
16:20781029:T:A	W280R	0.992
16:20781029:T:C	W280R	0.992
16:20781047:A:C	S286R	0.992
16:20781049:T:A	S286R	0.992
16:20781049:T:G	S286R	0.992
16:20785015:A:C	S351R	0.991
16:20785017:T:A	S351R	0.991
16:20785017:T:G	S351R	0.991
16:20770211:C:A	N59K	0.990
16:20770211:C:G	N59K	0.990
16:20781031:G:C	W280C	0.990
16:20781031:G:T	W280C	0.990
16:20781044:T:A	W285R	0.989
16:20781044:T:C	W285R	0.989
16:20792056:G:C	D461H	0.989
16:20792063:G:A	G463E	0.988
16:20796379:G:C	A522P	0.988
16:20780781:A:C	S236R	0.987
16:20780783:T:A	S236R	0.987
16:20780783:T:G	S236R	0.987
16:20786130:G:A	G399E	0.987
16:20792300:G:C	A507P	0.987

dbSNP variants (sampled 300 via entrez): RS1000001956 (16:20701420 C>T), RS1000031848 (16:20764302 T>G), RS1000038876 (16:20672940 AAC>A), RS1000044728 (16:20744120 C>G,T), RS1000049047 (16:20711573 G>A), RS1000114157 (16:20713365 T>C), RS1000126032 (16:20773376 A>C), RS1000186685 (16:20732465 G>T), RS1000187317 (16:20680262 C>A,G), RS1000195893 (16:20712001 TC>T), RS1000224579 (16:20720461 G>A), RS1000296370 (16:20793948 A>G), RS1000298469 (16:20720901 TTAACTA>T), RS1000342212 (16:20779047 G>A), RS1000344588 (16:20765766 C>T)

Disease associations

OMIM: gene MIM:145505 | disease phenotypes: MIM:619989

GenCC curated gene-disease

Mondo (2): neurodevelopmental disorder (MONDO:0700092), neurodevelopmental disorder with speech delay and variable ocular anomalies (MONDO:0859272)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003119_19	Urinary metabolites	3.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	6
sodium arsenite	affects methylation, decreases expression	4
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	increases methylation, affects expression, decreases expression	3
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Silicon Dioxide	decreases expression	2
sotorasib	decreases expression, affects cotreatment	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
ferrous chloride	increases expression	1
benazol P	affects expression	1
ciglitazone	affects binding, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	1
belinostat	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1

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