NOCT

Summary

NOCT (nocturnin, HGNC:14254) is a protein-coding gene on chromosome 4q31.1, encoding Nocturnin (Q9UK39). Phosphatase which catalyzes the conversion of NADP(+) to NAD(+) and of NADPH to NADH.

The protein encoded by this gene is highly similar to Nocturnin, a gene identified as a circadian clock regulated gene in Xenopus laevis. This protein and Nocturnin protein share similarity with the C-terminal domain of a yeast transcription factor, carbon catabolite repression 4 (CCR4). The mRNA abundance of a similar gene in mouse has been shown to exhibit circadian rhythmicity, which suggests a role for this protein in clock function or as a circadian clock effector.

Source: NCBI Gene 25819 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_012118

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14254
Approved symbol	NOCT
Name	nocturnin
Location	4q31.1
Locus type	gene with protein product
Status	Approved
Aliases	CCR4L, Ccr4c, NOC
Ensembl gene	ENSG00000151014
Ensembl biotype	protein_coding
OMIM	608468
Entrez	25819

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000280614, ENST00000515616, ENST00000630479, ENST00000866809

RefSeq mRNA: 1 — MANE Select: NM_012118 NM_012118

CCDS: CCDS3743

Canonical transcript exons

ENST00000280614 — 3 exons

Exon	Start	End
ENSE00000997224	139043074	139043343
ENSE00001147385	139044639	139045939
ENSE00001171305	139015781	139016171

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 93.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.8383 / max 1107.7725, expressed in 1808 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49727	34.0176	1807
49728	4.3559	978
49729	1.2913	332
49725	0.0972	36
49726	0.0763	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.57	gold quality
islet of Langerhans	UBERON:0000006	83.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.27	gold quality
stromal cell of endometrium	CL:0002255	79.16	gold quality
pancreatic ductal cell	CL:0002079	78.78	gold quality
muscle of leg	UBERON:0001383	77.99	gold quality
gall bladder	UBERON:0002110	77.92	gold quality
gastrocnemius	UBERON:0001388	77.71	gold quality
omental fat pad	UBERON:0010414	77.70	gold quality
secondary oocyte	CL:0000655	77.61	gold quality
peritoneum	UBERON:0002358	77.60	gold quality
right lobe of liver	UBERON:0001114	77.52	gold quality
bone marrow cell	CL:0002092	76.10	gold quality
adrenal tissue	UBERON:0018303	75.86	gold quality
adipose tissue of abdominal region	UBERON:0007808	75.78	gold quality
cortical plate	UBERON:0005343	75.22	gold quality
monocyte	CL:0000576	73.12	gold quality
prefrontal cortex	UBERON:0000451	73.12	gold quality
mononuclear cell	CL:0000842	72.99	gold quality
leukocyte	CL:0000738	72.86	gold quality
liver	UBERON:0002107	72.43	gold quality
ganglionic eminence	UBERON:0004023	72.43	gold quality
colonic epithelium	UBERON:0000397	72.40	gold quality
muscle organ	UBERON:0001630	72.14	gold quality
pancreas	UBERON:0001264	72.02	gold quality
vermiform appendix	UBERON:0001154	70.00	gold quality
tibialis anterior	UBERON:0001385	69.99	silver quality
blood	UBERON:0000178	69.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CLOCK, CREB1, FOXO1, PPARG

miRNA regulators (miRDB)

35 targeting NOCT, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-4475	97.36	66.95	761

Literature-anchored findings (GeneRIF, showing 11)

• A human lung cancer cell line SBC-5 that efficiently metastasized to bone when intravenously injected into SCID mice was found to express CCR4. (PMID:16821125)
• The transcription of human nocturnin gene displayed circadian oscillations in Huh7 cells (a human hepatoma cell line) and was regulated by CLOCK/BMAL1 heterodimer via the E-box of nocturnin promoter. (PMID:18587630)
• Ccr4d functions as an anti-proliferating protein through the induction of cell cycle arrest via a p21-dependent and p53-independent pathway and suggest that Ccr4d might have an important role in carcinogenesis. (PMID:22547059)
• Genetic variation in the NOC gene is associated with body mass index in Chinese subjects. (PMID:23922759)
• Three tag SNPs (rs938836, rs17050680, rs3805213) in the CCRN4L are significant correlation with genotype and allele frequency in lung cancer. (PMID:24821610)
• results highlight the clinical significance of PARN and NOC on the survival in SCC diagnosed patients. (PMID:26541675)
• NOCT is an exoribonuclease that can degrade mRNAs to inhibit protein expression (PMID:29860338)
• This review seeks to integrate these new discoveries into our understanding of Nocturnin’s regulatory functions and highlight the important remaining unanswered questions surrounding its regulation, biochemical activities, protein partners, and target mRNAs. (PMID:30257600)
• Study present a 2.7-A crystal structure of the catalytic domain of human NOCT. Our structure shows that NOCT has a close overall similarity to CCR4 deadenylase family members, PDE12 and CNOT6L, and to a DNA repair enzyme TDP2. All the key catalytic residues present in PDE12, CNOT6L and TDP2 are conserved in NOCT and have the same conformations. (PMID:30389976)
• Measuring NOCTURNIN expression levels in human peripheral blood lymphocytes can improve investigations on the relationship between changes in circadian rhythm and metabolic disorders. Shift workers show higher NOCTURNIN levels than daytime worker (PMID:31467910)
• Differential processing and localization of human Nocturnin controls metabolism of mRNA and nicotinamide adenine dinucleotide cofactors. (PMID:32839274)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nocta	ENSDARG00000077726
danio_rerio	noctb	ENSDARG00000078525
mus_musculus	Noct	ENSMUSG00000023087
rattus_norvegicus	Noct	ENSRNOG00000010799
drosophila_melanogaster	cu	FBGN0261808

Paralogs (5): ANGEL1 (ENSG00000013523), CNOT6 (ENSG00000113300), CNOT6L (ENSG00000138767), ANGEL2 (ENSG00000174606), PDE12 (ENSG00000174840)

Protein

Protein identifiers

Nocturnin — Q9UK39 (reviewed: Q9UK39)

Alternative names: Carbon catabolite repression 4-like protein

All UniProt accessions (2): Q9UK39, Q8WTX0

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatase which catalyzes the conversion of NADP(+) to NAD(+) and of NADPH to NADH. Shows a small preference for NADPH over NADP(+). Represses translation and promotes degradation of target mRNA molecules. Plays an important role in post-transcriptional regulation of metabolic genes under circadian control. Exerts a rhythmic post-transcriptional control of genes necessary for metabolic functions including nutrient absorption, glucose/insulin sensitivity, lipid metabolism, adipogenesis, inflammation and osteogenesis. Plays an important role in favoring adipogenesis over osteoblastogenesis and acts as a key regulator of the adipogenesis/osteogenesis balance. Promotes adipogenesis by facilitating PPARG nuclear translocation which activates its transcriptional activity. Regulates circadian expression of NOS2 in the liver and negatively regulates the circadian expression of IGF1 in the bone. Critical for proper development of early embryos.

Subunit / interactions. Interacts with PPARG.

Subcellular location. Cytoplasm. Nucleus. Perinuclear region. Mitochondrion.

Tissue specificity. Adipose tissue. Expression is higher in subcutaneous adipose tissue as compared to visceral adipose tissue.

Cofactor. Binds 2 magnesium ions, but the ions are only loosely bound to the protein.

Similarity. Belongs to the CCR4/nocturin family.

RefSeq proteins (1): NP_036250* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005135	Endo/exonuclease/phosphatase	Domain
IPR034965	Deadenylase_nocturnin	Domain
IPR036691	Endo/exonu/phosph_ase_sf	Homologous_superfamily
IPR050410	CCR4/nocturin_mRNA_transcr	Family

Pfam: PF03372

Enzyme classification (BRENDA):

• EC 3.1.3.108 — nocturnin (BRENDA: 7 organisms, 6 substrates, 2 inhibitors, 7 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADPH	0.098–0.77	4
NADP+	0.14–0.54	3

Catalyzed reactions (Rhea), 2 shown:

• NADP(+) + H2O = phosphate + NAD(+) (RHEA:28050)
• NADPH + H2O = phosphate + NADH (RHEA:60664)

UniProt features (67 total): strand 19, mutagenesis site 14, helix 10, binding site 7, sequence conflict 5, turn 5, region of interest 2, compositionally biased region 2, transit peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6BT1	X-RAY DIFFRACTION	1.48
6BT2	X-RAY DIFFRACTION	2.41
6MAL	X-RAY DIFFRACTION	2.6
6NF0	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UK39-F1	83.72	0.74

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 (7): 286–289; 324–326; 414; 195; 195; 219–221; 263

Mutagenesis-validated functional residues (14):

Position	Phenotype
149	slightly decreased activity as transcriptional repressor.
160	lack of catalytic activity.
195	slightly increased activity as transcriptional repressor. lack of catalytic activity.
219	reduced catalytic activity.
286	no effect on activity as transcriptional repressor.
286	lack of catalytic activity.
288	reduced catalytic activity.
290	lack of catalytic activity.
324	no effect on activity as transcriptional repressor.
326	no effect on activity as transcriptional repressor.
365	no effect on catalytic activity.
367	reduced catalytic activity.
377	slightly decreased activity as transcriptional repressor.
414	decreased activity as transcriptional repressor.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression

MSigDB gene sets: 0 (showing top):

GO Biological Process (15): deadenylation-dependent decapping of nuclear-transcribed mRNA (GO:0000290), transcription by RNA polymerase II (GO:0006366), NADP+ metabolic process (GO:0006739), negative regulation of gene expression (GO:0010629), response to lipopolysaccharide (GO:0032496), circadian regulation of gene expression (GO:0032922), P-body assembly (GO:0033962), regulation of circadian rhythm (GO:0042752), positive regulation of fat cell differentiation (GO:0045600), negative regulation of osteoblast differentiation (GO:0045668), regulation of embryonic development (GO:0045995), mRNA stabilization (GO:0048255), nucleobase-containing compound metabolic process (GO:0006139), circadian rhythm (GO:0007623), rhythmic process (GO:0048511)

GO Molecular Function (11): 3’-5’-RNA exonuclease activity (GO:0000175), mRNA binding (GO:0003729), poly(A)-specific ribonuclease activity (GO:0004535), NADP phosphatase activity (GO:0019178), metal ion binding (GO:0046872), NADPH phosphatase activity (GO:0102757), RNA binding (GO:0003723), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788)

GO Cellular Component (6): P-body (GO:0000932), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Circadian clock	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of gene expression	2
circadian rhythm	2
phosphatase activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
nuclear-transcribed mRNA catabolic process	1
mRNA methylguanosine-cap decapping	1
DNA-templated transcription	1
purine nucleotide metabolic process	1
nicotinamide nucleotide metabolic process	1
gene expression	1
negative regulation of macromolecule biosynthetic process	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
membraneless organelle assembly	1
regulation of biological process	1
fat cell differentiation	1
positive regulation of cell differentiation	1
regulation of fat cell differentiation	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
embryo development	1
regulation of multicellular organismal development	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
primary metabolic process	1
rhythmic process	1
biological_process	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
RNA binding	1
3’-5’-RNA exonuclease activity	1
cation binding	1
nucleic acid binding	1
molecular_function	1

Protein interactions and networks

STRING

957 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOCT	BMAL1	O00327	688
NOCT	PARN	O95453	684
NOCT	PER2	O15055	608
NOCT	NR1D1	P20393	585
NOCT	PNLDC1	Q8NA58	578
NOCT	CNOT8	Q9UFF9	562
NOCT	CLOCK	O15516	555
NOCT	THRA	P10827	548
NOCT	CRY1	Q16526	546
NOCT	PER3	P56645	546
NOCT	CRY2	Q49AN0	544
NOCT	DEDD	O75618	522
NOCT	CNOT7	Q9UIV1	510
NOCT	CNOT9	Q92600	509
NOCT	CNOT3	O75175	500

IntAct

58 interactions, top by confidence:

A	B	Type	Score
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
MAP2K2	TUBA4A	psi-mi:“MI:0914”(association)	0.640
NUP210	NOCT	psi-mi:“MI:0915”(physical association)	0.560
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
RAB8B	BLTP3B	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
CD79A	METTL15	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
MYO18A	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PDCD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
LRRTM1	TMEM223	psi-mi:“MI:0914”(association)	0.350
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
CHRM3		psi-mi:“MI:0914”(association)	0.350
SLC22A16	AGPAT2	psi-mi:“MI:0914”(association)	0.350
TRMT1	HDAC3	psi-mi:“MI:0914”(association)	0.350

BioGRID (66): CCRN4L (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), DBT (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), PINX1 (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), ETNK1 (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS)

ESM2 similar proteins: A0JPH4, A6H7I3, A8MS41, A9JRL3, B2RYM0, E1C3P4, F1ND48, O35710, O81916, P55265, P55266, P57097, P79942, P97573, Q09M05, Q0WKY2, Q149N8, Q1RMU2, Q2TBA3, Q4U2V3, Q5E9N9, Q5R6Z9, Q5RED8, Q5RGT6, Q5VTE6, Q5XIX3, Q60805, Q66H62, Q6DD21, Q6P549, Q7TPQ3, Q80TQ2, Q8K1C0, Q8K2I9, Q8K4J0, Q8NFZ0, Q8VCU0, Q96MI9, Q99MU3, Q99MV5

Diamond homologs: A8JQX3, O35710, P79942, Q9ET55, Q9UK39, Q5XH73, Q6IR85, Q8K1C0, A6H7I3, Q5RGT6, Q5VTE6, Q8VEG6, Q96LI5, A8MS41, B2RYM0, C4V7I7, O74874, Q08DF7, Q0WKY2, Q24239, Q4P9T3, Q6CEJ6, Q6L8Q7, Q8SU52, Q8VCU0, Q8VYU4, Q9LS39, Q9UNK9, A1CIJ6, A1CW67, A2BHJ4, A2Q9L0, P0CP22, P0CP23, P31384, Q0CT27, Q0U7W4, Q1EA11, Q2UUI3, Q4WQG5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

703 predictions. Top by Δscore:

Variant	Effect	Δscore
4:139043072:A:AG	acceptor_gain	1.0000
4:139043072:A:G	acceptor_loss	1.0000
4:139043073:G:GA	acceptor_gain	1.0000
4:139043073:GT:G	acceptor_gain	1.0000
4:139043073:GTGT:G	acceptor_gain	1.0000
4:139044634:TTCA:T	acceptor_loss	1.0000
4:139044636:CAGCT:C	acceptor_loss	1.0000
4:139044637:A:AG	acceptor_gain	1.0000
4:139044637:A:T	acceptor_loss	1.0000
4:139044638:G:GA	acceptor_gain	1.0000
4:139044638:GC:G	acceptor_gain	1.0000
4:139044638:GCT:G	acceptor_gain	1.0000
4:139044638:GCTC:G	acceptor_gain	1.0000
4:139044638:GCTCT:G	acceptor_gain	1.0000
4:139016172:G:A	donor_loss	0.9900
4:139016173:T:A	donor_loss	0.9900
4:139041799:GATTT:G	donor_gain	0.9900
4:139043069:C:CA	acceptor_gain	0.9900
4:139043072:AGT:A	acceptor_gain	0.9900
4:139043072:AGTGT:A	acceptor_gain	0.9900
4:139043073:GTG:G	acceptor_gain	0.9900
4:139043073:GTGTG:G	acceptor_gain	0.9900
4:139043220:G:GT	donor_gain	0.9900
4:139043339:CCAAG:C	donor_loss	0.9900
4:139043340:CAAGG:C	donor_loss	0.9900
4:139043341:AAG:A	donor_loss	0.9900
4:139043342:AGG:A	donor_loss	0.9900
4:139043345:T:A	donor_loss	0.9900
4:139043503:G:T	donor_gain	0.9800
4:139044635:TCAG:T	acceptor_gain	0.9800

AlphaMissense

2783 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:139043325:T:A	W148R	1.000
4:139043325:T:C	W148R	1.000
4:139043330:C:A	N149K	1.000
4:139043330:C:G	N149K	1.000
4:139044662:T:C	F162L	1.000
4:139044664:T:A	F162L	1.000
4:139044664:T:G	F162L	1.000
4:139044692:T:A	W172R	1.000
4:139044692:T:C	W172R	1.000
4:139044694:G:C	W172C	1.000
4:139044694:G:T	W172C	1.000
4:139044702:G:T	R175M	1.000
4:139044703:G:C	R175S	1.000
4:139044703:G:T	R175S	1.000
4:139044756:T:C	L193P	1.000
4:139044762:A:T	E195V	1.000
4:139044835:A:C	K219N	1.000
4:139044835:A:T	K219N	1.000
4:139044850:T:G	C224W	1.000
4:139044878:G:C	D234H	1.000
4:139044881:G:C	G235R	1.000
4:139044882:G:A	G235D	1.000
4:139044886:T:G	C236W	1.000
4:139044888:C:A	A237D	1.000
4:139044975:C:A	A266D	1.000
4:139045038:T:C	L287P	1.000
4:139045042:A:C	K288N	1.000
4:139045042:A:T	K288N	1.000
4:139045089:T:C	L304P	1.000
4:139045145:G:T	G323W	1.000

dbSNP variants (sampled 300 via entrez): RS1000016577 (4:139026721 T>C), RS1000030192 (4:139033309 G>A), RS1000053783 (4:139027594 G>T), RS1000361355 (4:139039335 A>G,T), RS1000437551 (4:139046354 C>T), RS1000553328 (4:139021492 C>G), RS1000576760 (4:139019947 G>A), RS1000631399 (4:139015719 G>T), RS1000683810 (4:139015835 A>G,T), RS1000978470 (4:139031805 C>T), RS1001000585 (4:139013940 C>G,T), RS1001031049 (4:139019689 T>C), RS1001141335 (4:139025655 G>A), RS1001238500 (4:139025277 G>C), RS1001326984 (4:139041608 A>G)

Disease associations

OMIM: gene MIM:608468 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006296_4	Response to ziprazidone in schizophrenia	3.000000e-06
GCST007576_131	Chronotype	1.000000e-09
GCST008839_348	Height	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Cisplatin	decreases expression, increases expression, affects cotreatment	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Asbestos, Crocidolite	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
titanium dioxide	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases abundance, increases expression	1
potassium chromate(VI)	increases expression, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
avobenzone	increases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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