AANAT

Summary

AANAT (aralkylamine N-acetyltransferase, HGNC:19) is a protein-coding gene on chromosome 17q25.1, encoding Serotonin N-acetyltransferase (Q16613). Controls the night/day rhythm of melatonin production in the pineal gland.

The protein encoded by this gene belongs to the acetyltransferase superfamily. It is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. Melatonin is essential for the function of the circadian clock that influences activity and sleep. This enzyme is regulated by cAMP-dependent phosphorylation that promotes its interaction with 14-3-3 proteins and thus protects the enzyme against proteasomal degradation. This gene may contribute to numerous genetic diseases such as delayed sleep phase syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 15 — RefSeq curated summary.

At a glance

• Gene–disease (curated): delayed sleep phase syndrome, susceptibility to (Limited, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 67 total — 5 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001088

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19
Approved symbol	AANAT
Name	aralkylamine N-acetyltransferase
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	SNAT
Ensembl gene	ENSG00000129673
Ensembl biotype	protein_coding
OMIM	600950
Entrez	15

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000250615, ENST00000392492, ENST00000585649, ENST00000587798, ENST00000878873, ENST00000915260, ENST00000915261, ENST00000970297

RefSeq mRNA: 2 — MANE Select: NM_001088 NM_001088, NM_001166579

CCDS: CCDS11745, CCDS54169

Canonical transcript exons

ENST00000392492 — 4 exons

Exon	Start	End
ENSE00000745230	76469173	76469327
ENSE00000745232	76469665	76470117
ENSE00001512157	76467603	76467727
ENSE00003475230	76468672	76468909

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 86.32.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8702 / max 1311.9859, expressed in 29 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162844	0.9947	18
162845	0.4858	16
162843	0.3558	18
162841	0.0186	3
162842	0.0154	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.54	gold quality
granulocyte	CL:0000094	75.87	gold quality
right testis	UBERON:0004534	71.26	gold quality
left testis	UBERON:0004533	71.03	gold quality
thymus	UBERON:0002370	70.43	silver quality
testis	UBERON:0000473	70.03	gold quality
monocyte	CL:0000576	68.94	gold quality
blood	UBERON:0000178	67.76	gold quality
leukocyte	CL:0000738	67.72	gold quality
cerebellar vermis	UBERON:0004720	65.99	gold quality
spleen	UBERON:0002106	65.31	gold quality
vermiform appendix	UBERON:0001154	65.21	gold quality
substantia nigra	UBERON:0002038	64.40	gold quality
spinal cord	UBERON:0002240	63.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	63.83	gold quality
lymph node	UBERON:0000029	63.41	gold quality
vastus lateralis	UBERON:0001379	60.86	gold quality
quadriceps femoris	UBERON:0001377	60.54	gold quality
hypothalamus	UBERON:0001898	59.89	gold quality
left uterine tube	UBERON:0001303	59.72	gold quality
metanephric glomerulus	UBERON:0004736	59.22	gold quality
trachea	UBERON:0003126	59.07	gold quality
dorsal plus ventral thalamus	UBERON:0001897	59.03	gold quality
left adrenal gland cortex	UBERON:0035825	58.71	gold quality
dorsal root ganglion	UBERON:0000044	58.67	gold quality
right adrenal gland cortex	UBERON:0035827	58.49	gold quality
bone marrow	UBERON:0002371	58.43	gold quality
Ammon’s horn	UBERON:0001954	58.37	gold quality
right frontal lobe	UBERON:0002810	58.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	1339.27
E-GEOD-137537	yes	19.08
E-ANND-3	no	1.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CREB1, CREM, CRX, FOS, JUN, NFKB, NPAS2

miRNA regulators (miRDB)

6 targeting AANAT, 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-4663	99.62	65.33	957
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-626	98.89	66.21	762
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-6777-3P	95.35	64.30	699

Literature-anchored findings (GeneRIF, showing 20)

• effect of FliI protein on actin remodelling is a vital part of cellular motility, contraction and adhesion. Exact signaling pathways and mechanisms underpinning FliI effects in wound healing are yet to be fully identified[review] (PMID:17526423)
• The results showed that Drosophila FliI regulates the expression of metabolic genes, and that dysregulation of the transcription controlled by FliI gives rise to metabolic stress and problems in the development and physiology of Drosophila. (PMID:30060781)
• The actin polymerization factor Diaphanous and the actin severing protein Flightless I collaborate to regulate sarcomere size. (PMID:32980309)
• Drosophila flightless-I gene, highly conserved in C. elegans and humans, is involved in gastrulation and muscle degeneration (PMID:8248259)
• The crystal structure of the gp15 hexamer is reported and its interactions are described in T4 virions that have either an extended tail or a contracted tail; its structural relationship to other phage proteins is discussed. (PMID:23434847)
• There is a significant increase in AANAT allele positivity at the single nucleotide polymorphism (alanine 129–> threonine) at between patients with DSPS & controls. AA-NAT could be a susceptibility gene for DSPS. (PMID:12736803)
• Data suggest that the -263G/C single nucleotide polymorphism of arylalkylamine-N-acetyl-transferase (AA-NAT) may be an important determinant of the late/short sleep pattern. (PMID:15332344)
• Single nucleotide polymorphisms in the AANAT gene identified thus far cannot explain the observed interindividual differences for nocturnal melatonin profiles in the subjects investigated. (PMID:18569588)
• AANAT polymorphisms were not associated with adolescent idiopathic scoliosis. (PMID:18794762)
• Identified 17 sequence changes in AANAT gene of patients with major depression. Show evidence of the association of genetic variability in the AANAT gene with susceptibility to major depression. (PMID:20459461)
• The functional expression of human SNA protein was closely associated with the elevated synthesis of N-acetylserotonin and melatonin in transgenic rice plants. (PMID:20586889)
• The expression of AANAT in epithelial cells of striated ducts in human submandibular glands. (PMID:21437622)
• There is dysregulation of the AANAT/ASMT/melatonin –> melatonin receptor axis in cholangiocarcinoma, which inhibited melatonin secretion and subsequently enhanced CCA growth. (PMID:21778461)
• these and related results indicate both a major involvement of the N-end rule pathway in the control of rodent AANATs and substantial differences in the regulation of rodent and human AANATs that stem from differences in their N-terminal sequences. (PMID:27339900)
• Data show that arylalkymine N-acetyltransferase (AANAT) levels and melatonin synthesis change after transient receptor potential channel 4 (TRPV4 channel) stimulation in ciliary body epithelial cells. (PMID:28368307)
• Aggregate genetic variation in circadian rhythm and melatonin pathways were significantly associated with the risk of prostate cancer in data combining GAME-ON and PLCO, after Bonferroni correction (ppathway < 0.00625). The two most significant genes were NPAS2 (pgene = 0.0062) and AANAT (pgene = 0.00078); the latter being significant after Bonferroni correction. (PMID:28699174)
• Two SNPs of AANAT gene (rs8150 and rs3760138) associated with the risk of systemic lupus erythematosus. (PMID:31815152)
• [Association of polymorphic variants of DDC (AADC), AANAT and ASMT genes encoding enzymes for melatonin synthesis with the higher risk of neuropsychiatric disorders].", trans “Assotsiatsiya polimorfizmov genov DDC (AADC), AANAT i ASMT, kodiruyushchikh fermenty sinteza melatonina, s riskom razvitiya psikhonevrologicheskikh rasstroistv. (PMID:34184492)
• Downregulation of AANAT by c-Fos in tubular epithelial cells with membranous nephropathy. (PMID:34763165)
• Variation in the AA-NAT gene G203A is associated with Awassi and Hamdani sheep fertility. (PMID:38753969)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	aanat1	ENSDARG00000036567
mus_musculus	Aanat	ENSMUSG00000020804
rattus_norvegicus	Aanat	ENSRNOG00000011182

Protein

Protein identifiers

Serotonin N-acetyltransferase — Q16613 (reviewed: Q16613)

Alternative names: Aralkylamine N-acetyltransferase

All UniProt accessions (4): Q16613, F1T0I5, K7ERF6, K7ESH7

UniProt curated annotations — full annotation on UniProt →

Function. Controls the night/day rhythm of melatonin production in the pineal gland. Catalyzes the N-acetylation of serotonin into N-acetylserotonin, the penultimate step in the synthesis of melatonin.

Subunit / interactions. Monomer. Interacts with several 14-3-3 proteins, including YWHAB, YWHAE, YWHAG and YWHAZ, preferentially when phosphorylated at Thr-31. Phosphorylation on Ser-205 also allows binding to YWHAZ, but with lower affinity. The interaction with YWHAZ considerably increases affinity for arylalkylamines and acetyl-CoA and protects the enzyme from dephosphorylation and proteasomal degradation. It may also prevent thiol-dependent inactivation.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in pineal gland and at lower levels in the retina. Weak expression in several brain regions and in the pituitary gland.

Post-translational modifications. cAMP-dependent phosphorylation on both N-terminal Thr-31 and C-terminal Ser-205 regulates AANAT activity by promoting interaction with 14-3-3 proteins.

Pathway. Aromatic compound metabolism; melatonin biosynthesis; melatonin from serotonin: step 1/2.

Similarity. Belongs to the acetyltransferase family. AANAT subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16613-1	1	yes
Q16613-2	2

RefSeq proteins (2): NP_001079, NP_001160051 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000182	GNAT_dom	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR051635	SNAT-like	Family

Pfam: PF00583

Enzyme classification (BRENDA):

• EC 2.3.1.87 — aralkylamine N-acetyltransferase (BRENDA: 46 organisms, 152 substrates, 81 inhibitors, 196 Km, 87 kcat entries)

Substrate kinetics (BRENDA)

48 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
TRYPTAMINE	0.0017–4.3	33
ACETYL-COA	0.0003–1.11	25
SEROTONIN	0.042–13	20
HISTAMINE	0.0023–16	13
OCTOPAMINE	0.002–30	9
DOPAMINE	0.0097–11	8
TYRAMINE	0.0015–57	7
5-HYDROXYTRYPTAMINE	0.024–0.314	6
NOREPINEPHRINE	0.05–0.38	6
2-PHENYLETHYLAMINE	0.17–9.5	3
5-METHOXYTRYPTAMINE	0.042–0.63	3
BUTANOYL-COA	0.0018–0.045	3
PROPIONYL-COA	0.066–0.47	3
2-(2,3-DICHLOROPHENYL)-ETHYLAMINE	0.34–3.46	2
2-(2-CHLOROPHENYL)-ETHYLAMINE	0.9–2.74	2

Catalyzed reactions (Rhea), 1 shown:

• a 2-arylethylamine + acetyl-CoA = an N-acetyl-2-arylethylamine + CoA + H(+) (RHEA:20497)

UniProt features (16 total): binding site 5, modified residue 2, sequence variant 2, site 2, chain 1, domain 1, splice variant 1, mutagenesis site 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6T80	X-RAY DIFFRACTION	2.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16613-F1	86.75	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 (2): 120 (important for the catalytic mechanism; involved in substrate deprotonation); 122 (important for the catalytic mechanism; involved in substrate deprotonation)

Ligand- & substrate-binding residues (5): 124–126; 124; 132–137; 159; 168–170

Post-translational modifications (2): 31, 205

Mutagenesis-validated functional residues (1):

Position	Phenotype
31	loss of activation by camp.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-209931	Serotonin and melatonin biosynthesis
R-HSA-1430728	Metabolism
R-HSA-209776	Metabolism of amine-derived hormones
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 154 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_CIRCADIAN_RHYTHM, RNGTGGGC_UNKNOWN, GOBP_N_TERMINAL_PROTEIN_AMINO_ACID_ACETYLATION, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MORF_FLT1, GOBP_RESPONSE_TO_ZINC_ION, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, GOBP_RESPONSE_TO_PEPTIDE, GOBP_PHOTOPERIODISM, GOBP_RESPONSE_TO_CORTICOSTEROID, MODULE_45, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RESPONSE_TO_COPPER_ION

GO Biological Process (17): N-terminal protein amino acid acetylation (GO:0006474), circadian rhythm (GO:0007623), response to light stimulus (GO:0009416), photoperiodism (GO:0009648), response to zinc ion (GO:0010043), melatonin biosynthetic process (GO:0030187), response to insulin (GO:0032868), response to cytokine (GO:0034097), response to prostaglandin E (GO:0034695), indolalkylamine biosynthetic process (GO:0046219), response to copper ion (GO:0046688), response to corticosterone (GO:0051412), response to calcium ion (GO:0051592), cellular response to cAMP (GO:0071320), rhythmic process (GO:0048511), response to cAMP (GO:0051591), response to peptide (GO:1901652)

GO Molecular Function (8): aralkylamine N-acetyltransferase activity (GO:0004059), arylamine N-acetyltransferase activity (GO:0004060), 14-3-3 protein binding (GO:0071889), protein binding (GO:0005515), N-acetyltransferase activity (GO:0008080), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of amine-derived hormones	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to metal ion	3
cellular anatomical structure	3
indole-containing compound biosynthetic process	2
response to alcohol	2
response to ketone	2
N-acetyltransferase activity	2
cytoplasm	2
protein acetylation	1
N-terminal protein amino acid modification	1
protein maturation	1
rhythmic process	1
response to radiation	1
response to light stimulus	1
melatonin metabolic process	1
hormone biosynthetic process	1
response to peptide hormone	1
response to peptide	1
response to prostaglandin	1
biogenic amine biosynthetic process	1
response to glucocorticoid	1
response to mineralocorticoid	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
biological_process	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
response to chemical	1
protein binding	1
binding	1
acetyltransferase activity	1
catalytic activity	1
transferase activity	1
acyltransferase activity	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1196 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AANAT	ASMT	P46597	940
AANAT	YWHAZ	P29213	929
AANAT	OPN4	Q9UHM6	853
AANAT	GLYATL1	Q969I3	776
AANAT	SLC38A2	Q96QD8	720
AANAT	ESCO1	Q5FWF5	715
AANAT	ESCO2	Q56NI9	714
AANAT	SLC38A1	Q9H2H9	696
AANAT	BMAL1	O00327	671
AANAT	SLC38A4	Q969I6	670
AANAT	PER2	O15055	656
AANAT	MTNR1A	P48039	654
AANAT	TPH1	P17752	651
AANAT	DDC	P20711	634
AANAT	TPH2	Q8IWU9	633

IntAct

26 interactions, top by confidence:

A	B	Type	Score
AANAT	BHLHE40	psi-mi:“MI:0915”(physical association)	0.720
MDFI	AANAT	psi-mi:“MI:0915”(physical association)	0.720
AANAT	MDFI	psi-mi:“MI:0915”(physical association)	0.720
GRB10	AANAT	psi-mi:“MI:0915”(physical association)	0.560
AANAT	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
AANAT	EIF4E3	psi-mi:“MI:0915”(physical association)	0.560
CIDEB	SNCG	psi-mi:“MI:0914”(association)	0.350
AANAT	UBB	psi-mi:“MI:0914”(association)	0.350
YWHAZ	AANAT	psi-mi:“MI:0914”(association)	0.350
AANAT	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.000
AANAT	GRB10	psi-mi:“MI:0915”(physical association)	0.000
EIF4E3	AANAT	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): MDFI (Two-hybrid), BHLHE40 (Two-hybrid), BHLHE40 (Two-hybrid), MDFI (Two-hybrid), TOP1 (Negative Genetic), SSTR5 (Negative Genetic), P2RY6 (Negative Genetic), SPHK1 (Positive Genetic), AANAT (Two-hybrid), EIF4E3 (Two-hybrid), KRTAP8-1 (Two-hybrid), AANAT (Co-crystal Structure), AANAT (Co-purification), UBB (Affinity Capture-MS), AANAT (Affinity Capture-MS)

ESM2 similar proteins: A5YM72, D3KCC4, D3ZUM2, D4ABH7, I3L5V6, O02785, O43304, O88816, O95382, O95398, O97756, P0DPD7, P0DPE0, P10938, P11086, P51657, P79774, Q16613, Q29495, Q29S19, Q32PY6, Q4KLI9, Q4KLY6, Q561R2, Q5IS55, Q5QJC3, Q5RFI3, Q60806, Q64666, Q6AY27, Q6PDS3, Q6SZW1, Q6VY05, Q6ZPS2, Q8BH02, Q8BH83, Q8C7W7, Q8IYX4, Q8VC03, Q91YP1

Diamond homologs: O02785, O88816, O97756, P79774, Q16613, Q29495, Q5IS55, Q64666, Q9R0A9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	AANAT	phosphorylation
serotonin	“up-regulates activity”	AANAT	“chemical activation”
AANAT	“up-regulates quantity”	N-acetylserotonin	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	43
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
4279221	GRCh37/hg19 17q24.3-25.3(chr17:70161447-81041938)x3	Pathogenic
443446	GRCh37/hg19 17q25.1-25.3(chr17:73951701-81041938)x3	Pathogenic
443488	GRCh37/hg19 17q24.2-25.3(chr17:67002415-81041938)x3	Pathogenic
564463	GRCh37/hg19 17q24.1-25.3(chr17:63689671-81041938)x3	Pathogenic
689209	GRCh37/hg19 17q24.1-25.3(chr17:62778720-81041938)x3	Pathogenic
624519	GRCh37/hg19 17q24.1-25.2(chr17:64159738-74891024)x3	Likely pathogenic

SpliceAI

518 predictions. Top by Δscore:

Variant	Effect	Δscore
17:76467725:CAGG:C	donor_loss	1.0000
17:76467726:AG:A	donor_loss	1.0000
17:76468669:CAGG:C	acceptor_loss	1.0000
17:76468670:A:AG	acceptor_gain	1.0000
17:76468671:G:GA	acceptor_loss	1.0000
17:76468671:G:GG	acceptor_gain	1.0000
17:76469325:CAGGT:C	donor_loss	1.0000
17:76469326:AGGTG:A	donor_loss	1.0000
17:76469327:GG:G	donor_loss	1.0000
17:76469328:GTG:G	donor_loss	1.0000
17:76469660:CCCA:C	acceptor_loss	1.0000
17:76469662:CAG:C	acceptor_loss	1.0000
17:76469664:GGA:G	acceptor_gain	1.0000
17:76468659:T:A	acceptor_gain	0.9900
17:76468667:A:AG	acceptor_gain	0.9900
17:76468670:AG:A	acceptor_gain	0.9900
17:76468670:AGGT:A	acceptor_gain	0.9900
17:76468671:GG:G	acceptor_gain	0.9900
17:76468671:GGT:G	acceptor_gain	0.9900
17:76468671:GGTG:G	acceptor_gain	0.9900
17:76468671:GGTGC:G	acceptor_gain	0.9900
17:76468910:G:GA	donor_loss	0.9900
17:76468910:G:GG	donor_gain	0.9900
17:76468911:T:G	donor_loss	0.9900
17:76469076:T:TA	acceptor_gain	0.9900
17:76469077:G:A	acceptor_gain	0.9900
17:76469083:C:CA	acceptor_gain	0.9900
17:76469084:G:A	acceptor_gain	0.9900
17:76469171:A:AG	acceptor_gain	0.9900
17:76469172:G:GG	acceptor_gain	0.9900

AlphaMissense

1341 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:76469262:T:C	F85L	0.962
17:76469264:C:A	F85L	0.962
17:76469264:C:G	F85L	0.962
17:76469175:T:C	F56L	0.957
17:76469177:C:A	F56L	0.957
17:76469177:C:G	F56L	0.957
17:76469286:T:C	F93L	0.956
17:76469288:C:A	F93L	0.956
17:76469288:C:G	F93L	0.956
17:76469908:T:C	F188L	0.940
17:76469910:C:A	F188L	0.940
17:76469910:C:G	F188L	0.940
17:76469863:T:C	F173L	0.931
17:76469865:C:A	F173L	0.931
17:76469865:C:G	F173L	0.931
17:76468855:T:C	F37L	0.919
17:76468857:T:A	F37L	0.919
17:76468857:T:G	F37L	0.919
17:76469845:T:C	F167L	0.915
17:76469847:C:A	F167L	0.915
17:76469847:C:G	F167L	0.915
17:76469226:T:C	F73L	0.914
17:76469228:C:A	F73L	0.914
17:76469228:C:G	F73L	0.914
17:76468902:G:C	E52D	0.908
17:76468902:G:T	E52D	0.908
17:76468891:T:C	F49L	0.900
17:76468893:T:A	F49L	0.900
17:76468893:T:G	F49L	0.900
17:76469259:T:A	W84R	0.879

dbSNP variants (sampled 300 via entrez): RS1000264570 (17:76456668 A>C,T), RS1000319825 (17:76468133 A>T), RS1000553110 (17:76466726 C>G,T), RS1000623179 (17:76467810 A>G), RS1000795618 (17:76466493 CG>C,CGG), RS1001200426 (17:76461963 C>T), RS1001262500 (17:76455939 G>C), RS1001344102 (17:76467280 C>G), RS1001494762 (17:76455327 T>C), RS1001607925 (17:76461914 A>G), RS1001790349 (17:76467469 C>T), RS1002378306 (17:76451756 A>G), RS1002451600 (17:76457285 A>C), RS1002690818 (17:76454897 C>A,G,T), RS1002770225 (17:76456174 A>T)

Disease associations

OMIM: gene MIM:600950 | disease phenotypes: MIM:614163

GenCC curated gene-disease

Disease	Classification	Inheritance
delayed sleep phase syndrome, susceptibility to	Limited	Autosomal dominant

Mondo (1): delayed sleep phase syndrome, susceptibility to (MONDO:0800001)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004611_130	High light scatter reticulocyte count	3.000000e-21
GCST004612_78	High light scatter reticulocyte percentage of red cells	2.000000e-21
GCST90002385_322	High light scatter reticulocyte count	4.000000e-11
GCST90002386_197	High light scatter reticulocyte percentage of red cells	4.000000e-13
GCST90002387_200	Immature fraction of reticulocytes	4.000000e-14
GCST90002390_537	Mean corpuscular hemoglobin	3.000000e-13
GCST90002396_673	Mean reticulocyte volume	4.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196091 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

3 measured of 15 human assays (15 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
AANAT bisubstrate analog, 3	KI	32 nM
AANAT bisubstrate analog, 1	KI	48 nM
AANAT bisubstrate analog, 2	KI	67 nM

ChEMBL bioactivities

6 potent at pChembl≥5 of 7 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.32	Ki	48	nM	CHEMBL1231884
6.82	IC50	150	nM	CHEMBL1231884
6.75	IC50	180	nM	CHEMBL6132947
6.30	IC50	500	nM	CHEMBL290406
6.21	IC50	610	nM	CHEMBL6141798
5.28	IC50	5200	nM	CHEMBL6152629

PubChem BioAssay actives

14 with measured affinity, of 15 total; 14 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
[[(2R,3S,4S)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-3-hydroxy-4-[[3-[2-[6-(1H-indol-3-yl)-3-oxohexyl]sulfanylethylamino]-3-oxopropyl]amino]-2,2-dimethyl-4-oxobutyl] hydrogen phosphate	1799641: Spectrophotometric Assay from Article 10.1016/S0045-2068(03)00081-6: “Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: the importance of being neutral.”	ki	0.0320	uM
[[(2R,3S,4S)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-4-[[3-[2-[2-[2-(4,7-dihydro-1H-indol-3-yl)ethylamino]-2-oxoethyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl] hydrogen phosphate	1799641: Spectrophotometric Assay from Article 10.1016/S0045-2068(03)00081-6: “Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: the importance of being neutral.”	ki	0.0480	uM
[[(2R,3S,4S)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-4-[[3-[2-[3-[2-(4,7-dihydro-1H-indol-3-yl)ethylamino]-3-oxopropyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl] hydrogen phosphate	1799641: Spectrophotometric Assay from Article 10.1016/S0045-2068(03)00081-6: “Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: the importance of being neutral.”	ki	0.0670	uM
2-bromo-N-[2-(5-hydroxy-1-benzothiophen-3-yl)ethyl]acetamide	1799670: AANAT Assay from Article 10.1080/1475636021000005721: “Design, synthesis and in vitro evaluation of novel derivatives as serotonin N-acetyltransferase inhibitors.”	ic50	0.1800	uM
[[(2R,3S,4S)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-3-hydroxy-4-[[3-[2-[4-(1H-indol-3-yl)butylsulfanyl]ethylamino]-3-oxopropyl]amino]-2,2-dimethyl-4-oxobutyl] hydrogen phosphate	1799641: Spectrophotometric Assay from Article 10.1016/S0045-2068(03)00081-6: “Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: the importance of being neutral.”	ki	0.3100	uM
[[(2R,3S,4S)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-3-hydroxy-4-[[3-[2-[5-(1H-indol-3-yl)pentylsulfanyl]ethylamino]-3-oxopropyl]amino]-2,2-dimethyl-4-oxobutyl] hydrogen phosphate	1799641: Spectrophotometric Assay from Article 10.1016/S0045-2068(03)00081-6: “Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: the importance of being neutral.”	ki	0.3600	uM
2-bromo-N-[2-(5-fluoro-1-benzothiophen-3-yl)ethyl]acetamide	1799670: AANAT Assay from Article 10.1080/1475636021000005721: “Design, synthesis and in vitro evaluation of novel derivatives as serotonin N-acetyltransferase inhibitors.”	ic50	0.3900	uM
2-bromo-N-[2-(5-methoxy-1-benzothiophen-3-yl)ethyl]acetamide	1799670: AANAT Assay from Article 10.1080/1475636021000005721: “Design, synthesis and in vitro evaluation of novel derivatives as serotonin N-acetyltransferase inhibitors.”	ic50	0.6100	uM
N-[2-(1-benzothiophen-3-yl)ethyl]-2-bromoacetamide	1799670: AANAT Assay from Article 10.1080/1475636021000005721: “Design, synthesis and in vitro evaluation of novel derivatives as serotonin N-acetyltransferase inhibitors.”	ic50	0.6800	uM
2-bromo-N-[2-(5-ethyl-1-benzothiophen-3-yl)ethyl]acetamide	1799670: AANAT Assay from Article 10.1080/1475636021000005721: “Design, synthesis and in vitro evaluation of novel derivatives as serotonin N-acetyltransferase inhibitors.”	ic50	0.7000	uM
[[(2R,3S,4S)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R)-3-hydroxy-4-[[3-[2-[3-(1H-indol-3-yl)propylsulfanyl]ethylamino]-3-oxopropyl]amino]-2,2-dimethyl-4-oxobutyl] hydrogen phosphate	1799641: Spectrophotometric Assay from Article 10.1016/S0045-2068(03)00081-6: “Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: the importance of being neutral.”	ki	0.8400	uM
2-bromo-N-[2-(1H-indol-3-yl)ethyl]acetamide	1799670: AANAT Assay from Article 10.1080/1475636021000005721: “Design, synthesis and in vitro evaluation of novel derivatives as serotonin N-acetyltransferase inhibitors.”	ic50	1.4300	uM
2-bromo-N-[2-(5-bromo-1-benzothiophen-3-yl)ethyl]acetamide	1799670: AANAT Assay from Article 10.1080/1475636021000005721: “Design, synthesis and in vitro evaluation of novel derivatives as serotonin N-acetyltransferase inhibitors.”	ic50	3.7800	uM
3-[2-[3-[[(2R)-4-[[[(2R,3S,4S)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethylsulfanyl]propyl-[2-(1H-indol-3-yl)ethyl]azanium	1799641: Spectrophotometric Assay from Article 10.1016/S0045-2068(03)00081-6: “Novel bisubstrate analog inhibitors of serotonin N-acetyltransferase: the importance of being neutral.”	ki	5.8400	uM

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
uranyl acetate	affects expression	1
propionaldehyde	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Uranium	affects expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6084868	Binding	Inhibition of AANAT (unknown origin)	AANAT kinetics of CoASH-targeted electrophiles of tryptamine and related analogs. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_LH55	CHO-hAANAT	Spontaneously immortalized cell line	Female
CVCL_LH58	COS-7 1E7	Transformed cell line	Male

Clinical trials (associated diseases)

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