NUCKS1

Summary

NUCKS1 (nuclear casein kinase and cyclin dependent kinase substrate 1, HGNC:29923) is a protein-coding gene on chromosome 1q32.1, encoding Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (Q9H1E3). Chromatin-associated protein involved in DNA repair by promoting homologous recombination (HR).

This gene encodes a nuclear protein that is highly conserved in vertebrates. The conserved regions of the protein contain several consensus phosphorylation sites for casein kinase II and cyclin-dependent kinases, two putative nuclear localization signals, and a basic DNA-binding domain. It is phosphorylated in vivo by Cdk1 during mitosis of the cell cycle.

Source: NCBI Gene 64710 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_022731

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29923
Approved symbol	NUCKS1
Name	nuclear casein kinase and cyclin dependent kinase substrate 1
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	NUCKS
Ensembl gene	ENSG00000069275
Ensembl biotype	protein_coding
OMIM	611912
Entrez	64710

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000367142, ENST00000464938, ENST00000875217, ENST00000875218, ENST00000937279, ENST00000937280

RefSeq mRNA: 1 — MANE Select: NM_022731 NM_022731

CCDS: CCDS30987

Canonical transcript exons

ENST00000367142 — 7 exons

Exon	Start	End
ENSE00001069372	205727700	205727805
ENSE00001133436	205723926	205723981
ENSE00001381812	205720501	205720653
ENSE00001388725	205729572	205729621
ENSE00001443624	205749957	205750182
ENSE00001642294	205712822	205718479
ENSE00002290643	205719527	205719676

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.6070 / max 1285.2682, expressed in 1816 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17029	50.7734	1815
17028	12.2665	1678
17030	1.7488	1076
201900	1.5640	1001
17019	0.8855	534
17020	0.2545	68
17018	0.1141	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.95	gold quality
parietal pleura	UBERON:0002400	99.88	gold quality
medial globus pallidus	UBERON:0002477	99.87	gold quality
germinal epithelium of ovary	UBERON:0001304	99.84	gold quality
globus pallidus	UBERON:0001875	99.83	gold quality
visceral pleura	UBERON:0002401	99.83	gold quality
middle temporal gyrus	UBERON:0002771	99.81	gold quality
lateral globus pallidus	UBERON:0002476	99.76	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.71	gold quality
seminal vesicle	UBERON:0000998	99.68	gold quality
tibia	UBERON:0000979	99.67	gold quality
substantia nigra pars compacta	UBERON:0001965	99.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.64	gold quality
inferior vagus X ganglion	UBERON:0005363	99.63	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.61	gold quality
caput epididymis	UBERON:0004358	99.60	gold quality
renal medulla	UBERON:0000362	99.58	gold quality
ventral tegmental area	UBERON:0002691	99.58	gold quality
corpus epididymis	UBERON:0004359	99.56	gold quality
cauda epididymis	UBERON:0004360	99.56	gold quality
cranial nerve II	UBERON:0000941	99.52	gold quality
superior vestibular nucleus	UBERON:0007227	99.49	gold quality
entorhinal cortex	UBERON:0002728	99.46	gold quality
trigeminal ganglion	UBERON:0001675	99.44	gold quality
pleura	UBERON:0000977	99.42	gold quality
pylorus	UBERON:0001166	99.41	gold quality
pons	UBERON:0000988	99.40	gold quality
medulla oblongata	UBERON:0001896	99.40	gold quality
nipple	UBERON:0002030	99.38	gold quality
subthalamic nucleus	UBERON:0001906	99.37	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	2434.59
E-CURD-79	yes	1803.13
E-MTAB-7037	yes	349.61
E-CURD-114	yes	62.29
E-CURD-112	yes	44.27
E-HCAD-10	yes	36.83
E-CURD-122	yes	25.65
E-GEOD-125970	yes	23.59
E-MTAB-7316	yes	16.99
E-MTAB-8142	yes	15.11
E-MTAB-10042	yes	11.73
E-MTAB-10553	yes	8.93
E-CURD-88	yes	5.53
E-MTAB-11121	no	2084.96
E-MTAB-8530	no	1631.80

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
INSR	Unknown

miRNA regulators (miRDB)

238 targeting NUCKS1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784

Literature-anchored findings (GeneRIF, showing 33)

• Two putative nuclear localization signals have been identified and characterized in NUCKS. (PMID:17604136)
• NUCKS appears to have the highest ratio of modified to unmodified residues of any protein so far described. (PMID:18491381)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• The results show overexpression of the NUCKS protein and RNA in a number of non malignant breast lesions and cancerous tissues. In particular, the NUCKS overexpression in ADH and DCIS indicates a significant role of this protein in neoplastic progression. (PMID:19664271)
• Overexpression of NUCKS can play significant role in breast cancer biology. (PMID:20069058)
• Through a combination of gene expression and copy number analysis, NUCKS1 was identified as a candidate gene involved in the distant metastasis of colorectal cancer. (PMID:23065711)
• The expression of Nucks in both proliferating and quiescent cells and its correlation with Bax levels and apoptosis strongly suggest that Nucks plays complex roles in cell homeostasis. (PMID:24140890)
• Authors suggest that NUCKS is involved in cellular responses following PDT. (PMID:24284105)
• NUCKS-1 overexpression is associated with obesity and with breast cancer. (PMID:24568505)
• NUCKS1 overexpression may be associated with tumour progression and recurrence in cervical squamous cell carcinoma (PMID:24819170)
• NUCKS is a physiological regulator of energy homeostasis and glucose metabolism that works by regulating chromatin accessibility and RNA polymerase II recruitment to the promoters of IR and other insulin pathway modulators. (PMID:24931609)
• NUCKS1 expression did not increase Tat nuclear localization. (PMID:25116364)
• We would like to emphasize that NUCKS abundance in malignant skin tumors is higher than that of the well-known proliferation marker Ki67, thus allowing more precise assessment of tumor proliferation potential. (PMID:25119009)
• The results show that NUCKS1 is a chromatin-associated protein with a role in the DNA damage response and in homologous recombination, a DNA repair pathway critical for tumor suppression. (PMID:26323318)
• NUCKS1 was identified as a potential oncogene at chromosomal 1q32.1 in patients with HCC, and it might be a valuable immunodiagnostic marker for HCC (PMID:26968889)
• High NUCKS1 expression is associated with drug resistance in lung cancer. (PMID:26989074)
• Chinese patients with allele T of rs951366 on the NUCKS1 gene are more vulnerable to the incidence of adolescent idiopathic sclerosis as well as late onset of menarche. (PMID:28338576)
• NUCKS overexpression had prognostic potential for overall survival and disease-free survival in advanced ovarian cancers and only for disease-free survival in early ovarian cancers . Our data suggest that NUCKS overexpression may contribute to progression and poor prognosis in ovarian cancer especially in advanced ovarian cancer (PMID:28877654)
• NUCKS1 may be involved in DNA double-strand breakage repair and/or inflammatory signaling in ulcerative colitis (PMID:29462394)
• our results suggested that there was a significant association of a minor allele (G) in rs823114 with reduced risk of Parkinson’s disease development (P = 0.017, OR = 0.768, 95%CI = 0.618 - 0.955). We conclude that NUCKS1 rs823114 indicates a decreased risk of susceptibility to Parkinson’s disease and shows a male genetic distribution bias in the Han Chinese population. (PMID:29607885)
• The insulin-like growth factor 1 receptor (IGF-1R) gene was found to be a potential downstream target of NUCKS1 in GC cells. (PMID:30371738)
• NUCKS1 promotes RAD54 activity in homologous recombination DNA repair. (PMID:32876692)
• NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer. (PMID:32958058)
• NUCKS1 Acts as a Promising Novel Biomarker for the Prognosis of Patients with Hepatocellular Carcinoma. (PMID:33601927)
• Upregulation of NUCKS1 in Lung Adenocarcinoma is Associated with a Poor Prognosis. (PMID:33683970)
• Nucks1 gene polymorphism rs823114 is associated with the positive symptoms and neurocognitive function of patients with schizophrenia in parts of southern China. (PMID:34030174)
• NUCKS Promotes the Proliferation, Migration and Invasion of Lung Cancer Cells Through Pi3k/Akt Signalling Pathway. (PMID:34152708)
• The NUCKS1-SKP2-p21/p27 axis controls S phase entry. (PMID:34845229)
• CircRNA circ_0008037 facilitates tumor growth and the Warburg effect via upregulating NUCKS1 by binding to miR-433-3p in non-small cell lung cancer. (PMID:34850570)
• miR-641 Inhibited Cell Proliferation and Induced Apoptosis by Targeting NUCKS1/PI3K/AKT Signaling Pathway in Breast Cancer. (PMID:35069784)
• NUCKS1 promotes the progression of colorectal cancer via activating PI3K/AKT/mTOR signaling pathway. (PMID:37226932)
• Roles of increased NUCKS1 expression in endometriosis. (PMID:37582772)
• NUCB2 inhibition antagonizes osteosarcoma progression and promotes anti-tumor immunity through inactivating NUCKS1/CXCL8 axis. (PMID:38636892)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nucks1b	ENSDARG00000012777
danio_rerio	nucks1a	ENSDARG00000078473
mus_musculus	Nucks1	ENSMUSG00000026434
rattus_norvegicus	LOC120093168	ENSRNOG00000004262
rattus_norvegicus	Nucks1	ENSRNOG00000047287

Paralogs (1): RAD51AP1 (ENSG00000111247)

Protein

Protein identifiers

Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 — Q9H1E3 (reviewed: Q9H1E3)

Alternative names: P1

All UniProt accessions (1): Q9H1E3

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin-associated protein involved in DNA repair by promoting homologous recombination (HR). Binds double-stranded DNA (dsDNA) and secondary DNA structures, such as D-loop structures, but with less affinity than RAD51AP1.

Subunit / interactions. Does not interact with RAD51.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Widely expressed, with highest levels in thyroid gland, prostate and uterus and in fetal liver, thymus and lung.

Post-translational modifications. Phosphorylated in an ATM-dependent manner in response to DNA damage. Phosphorylated by CDK1 and casein kinase.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H1E3-1	1	yes
Q9H1E3-2	2

RefSeq proteins (1): NP_073568* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR052003	HR_DNA-Binding_Protein	Family

UniProt features (37 total): modified residue 23, compositionally biased region 8, sequence variant 2, chain 1, region of interest 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1E3-F1	58.25	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (23): 13, 14, 19, 26, 54, 58, 61, 73, 75, 79, 113, 130, 132, 144, 179, 181, 202, 204, 214, 223 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 338 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_IONIZING_RADIATION, HORIUCHI_WTAP_TARGETS_DN, CCAWYNNGAAR_UNKNOWN, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_TRANSCRIPTION, AAGCCAT_MIR135A_MIR135B, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GCM_BCL2L1

GO Biological Process (18): double-strand break repair via homologous recombination (GO:0000724), intracellular glucose homeostasis (GO:0001678), regulation of DNA replication (GO:0006275), chromatin organization (GO:0006325), replication fork processing (GO:0031297), gene conversion (GO:0035822), interstrand cross-link repair (GO:0036297), host-mediated activation of viral transcription (GO:0043923), host-mediated perturbation of viral genome replication (GO:0044827), host-mediated activation of viral genome replication (GO:0044829), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of insulin receptor signaling pathway (GO:0046626), positive regulation of insulin receptor signaling pathway (GO:0046628), regulation of DNA strand elongation (GO:0060382), cellular response to X-ray (GO:0071481), DNA repair (GO:0006281), DNA damage response (GO:0006974), glucose homeostasis (GO:0042593)

GO Molecular Function (7): chromatin binding (GO:0003682), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of DNA metabolic process	2
host-mediated activation of viral process	2
positive regulation of DNA-templated transcription	2
insulin receptor signaling pathway	2
binding	2
DNA binding	2
nuclear lumen	2
intracellular membraneless organelle	2
recombinational repair	1
double-strand break repair	1
glucose homeostasis	1
intracellular chemical homeostasis	1
DNA replication	1
cellular component organization	1
DNA-templated DNA replication maintenance of fidelity	1
homologous recombination	1
DNA repair	1
host-mediated perturbation of viral transcription	1
host-mediated perturbation of viral process	1
host-mediated perturbation of viral genome replication	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
regulation of signal transduction	1
positive regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
positive regulation of cellular response to insulin stimulus	1
DNA strand elongation	1
response to X-ray	1
cellular response to ionizing radiation	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
carbohydrate homeostasis	1
transcription coregulator activity	1
nucleic acid binding	1
transcription factor binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUCKS1	RAB29	O14966	928
NUCKS1	PM20D1	Q6GTS8	927
NUCKS1	SLC41A1	Q8IVJ1	917
NUCKS1	SLC45A3	Q96JT2	803
NUCKS1	LRRK2	Q5S007	658
NUCKS1	CDK1	P06493	605
NUCKS1	SNCA	P37840	572
NUCKS1	MAPT	P10636	538
NUCKS1	TMEM175	Q9BSA9	506
NUCKS1	MCCC1	Q96RQ3	447
NUCKS1	FAM47E	Q6ZV65	445
NUCKS1	KPNA4	O00629	428
NUCKS1	POC5	Q8NA72	400
NUCKS1	ACMSD	Q8TDX5	395
NUCKS1	TOMM40	O96008	391

IntAct

25 interactions, top by confidence:

A	B	Type	Score
SLC30A5	SLC30A6	psi-mi:“MI:0914”(association)	0.840
GLP1R	NUCKS1	psi-mi:“MI:0915”(physical association)	0.510
MME		psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
TRIM24	DDTL	psi-mi:“MI:0914”(association)	0.350
PRKACG	HAX1	psi-mi:“MI:0914”(association)	0.350
RIPK4	TBCA	psi-mi:“MI:0914”(association)	0.350
RB1	EIF5B	psi-mi:“MI:0914”(association)	0.350
rep	HMGN4	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
NEK10		psi-mi:“MI:0914”(association)	0.350
NUCKS1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
SMARCB1	KIF2A	psi-mi:“MI:2364”(proximity)	0.270
SMARCB1	FAM186A	psi-mi:“MI:2364”(proximity)	0.270
CDC14B	PES1	psi-mi:“MI:2364”(proximity)	0.270
RO60	NACA	psi-mi:“MI:2364”(proximity)	0.270
NUCKS1	MDM2	psi-mi:“MI:0915”(physical association)	0.000
DOCK9	NUCKS1	psi-mi:“MI:0915”(physical association)	0.000
NUCKS1	AK5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (254): COPS2 (Co-fractionation), HEXIM1 (Co-fractionation), HUWE1 (Co-fractionation), NUCKS1 (Co-fractionation), PHAX (Co-fractionation), NUCKS1 (Proximity Label-MS), NUCKS1 (Biochemical Activity), NUCKS1 (Affinity Capture-MS), NUCKS1 (Proximity Label-MS), NUCKS1 (Affinity Capture-MS), NUCKS1 (Proximity Label-MS), NUCKS1 (Affinity Capture-MS), NUCKS1 (Affinity Capture-MS), AK5 (Two-hybrid), NUCKS1 (Proximity Label-MS)

ESM2 similar proteins: A1CQS5, A1D3N8, A2QPM6, A3LXX5, A4QYF9, A5DLG8, A5E145, A5PLC8, A6SMQ7, A6ZQX9, A7ER98, A7TR90, A8N7N4, B0D1Q8, F4IP06, G0S8I1, G0SC91, O14210, P34618, P38439, P40019, P49379, P91753, Q05021, Q05913, Q0C807, Q0V3E0, Q10239, Q1E4L8, Q29S11, Q2GNS7, Q2UBH8, Q4WJ31, Q4WRE2, Q54MB8, Q59RN6, Q5B2V2, Q6BSE7, Q6CF40, Q6CFG6

Diamond homologs: A0A3Q2UEI8, Q29S11, Q80XU3, Q8C551, Q96B01, Q9EPJ0, Q9H1E3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NUCKS1	up-regulates	DNA_repair
CDK1	“down-regulates activity”	NUCKS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
learning or memory	5	37.6×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1170 predictions. Top by Δscore:

Variant	Effect	Δscore
1:205718308:TCAG:T	donor_gain	1.0000
1:205718475:CGTCA:C	acceptor_gain	1.0000
1:205718476:GTCA:G	acceptor_gain	1.0000
1:205718477:TCA:T	acceptor_gain	1.0000
1:205718478:CA:C	acceptor_gain	1.0000
1:205718478:CAC:C	acceptor_gain	1.0000
1:205718479:AC:A	acceptor_loss	1.0000
1:205718480:C:CC	acceptor_gain	1.0000
1:205718480:CTG:C	acceptor_loss	1.0000
1:205718481:T:C	acceptor_loss	1.0000
1:205718486:A:AC	acceptor_gain	1.0000
1:205718486:A:C	acceptor_gain	1.0000
1:205719523:TTA:T	donor_loss	1.0000
1:205719524:TACCT:T	donor_loss	1.0000
1:205719525:A:C	donor_loss	1.0000
1:205719526:C:A	donor_loss	1.0000
1:205719584:TCTTA:T	donor_gain	1.0000
1:205719672:ATCTT:A	acceptor_gain	1.0000
1:205719673:TCTTC:T	acceptor_gain	1.0000
1:205719674:CTT:C	acceptor_gain	1.0000
1:205719674:CTTCT:C	acceptor_gain	1.0000
1:205719675:TT:T	acceptor_gain	1.0000
1:205719675:TTCTG:T	acceptor_loss	1.0000
1:205719676:TC:T	acceptor_loss	1.0000
1:205719677:C:CC	acceptor_gain	1.0000
1:205719677:CTGA:C	acceptor_loss	1.0000
1:205719678:T:G	acceptor_loss	1.0000
1:205720493:T:TA	donor_gain	1.0000
1:205720496:CATA:C	donor_gain	1.0000
1:205720498:TAC:T	donor_loss	1.0000

AlphaMissense

1620 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:205720571:T:A	R104S	1.000
1:205720571:T:G	R104S	1.000
1:205720572:C:G	R104T	1.000
1:205720588:C:G	A99P	1.000
1:205720589:T:A	K98N	1.000
1:205720589:T:G	K98N	1.000
1:205720596:G:T	A96E	1.000
1:205720600:C:G	A95P	1.000
1:205729602:A:G	Y13H	1.000
1:205719532:G:T	A176D	0.999
1:205719540:T:A	R173S	0.999
1:205719540:T:G	R173S	0.999
1:205719651:G:C	F136L	0.999
1:205719651:G:T	F136L	0.999
1:205719653:A:G	F136L	0.999
1:205720572:C:A	R104I	0.999
1:205720574:C:A	Q103H	0.999
1:205720574:C:G	Q103H	0.999
1:205720575:T:G	Q103P	0.999
1:205720577:T:A	K102N	0.999
1:205720577:T:G	K102N	0.999
1:205720582:A:G	S101P	0.999
1:205720584:G:T	A100D	0.999
1:205720587:G:T	A99E	0.999
1:205720588:C:T	A99T	0.999
1:205720590:T:A	K98I	0.999
1:205720591:T:C	K98E	0.999
1:205720593:G:A	S97F	0.999
1:205720594:A:G	S97P	0.999
1:205720597:C:G	A96P	0.999

dbSNP variants (sampled 300 via entrez): RS1000056285 (1:205745013 C>A), RS1000131928 (1:205744064 T>C), RS1000205082 (1:205724950 T>C), RS1000232199 (1:205744305 T>C,G), RS1000244953 (1:205714059 A>C,G), RS1000306429 (1:205720838 G>A), RS1000506919 (1:205726408 T>C), RS1000575053 (1:205718555 A>G), RS1000640497 (1:205718898 T>C), RS1000649294 (1:205728008 T>C), RS1000789813 (1:205733133 T>C), RS1000862804 (1:205712445 G>A,C), RS1000883075 (1:205739306 T>C), RS1000922995 (1:205725885 T>C), RS1000923578 (1:205749577 G>A)

Disease associations

OMIM: gene MIM:611912 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000528_7	Parkinson’s disease	7.000000e-08
GCST000530_4	Parkinson’s disease	2.000000e-12
GCST001796_1	Prostate-specific antigen levels	2.000000e-19
GCST001875_2	Pubertal anthropometrics	2.000000e-07
GCST002500_40	QT interval	6.000000e-07
GCST002541_35	Menarche (age at onset)	2.000000e-08
GCST002544_11	Parkinson’s disease	2.000000e-16
GCST002703_5	Prostate-specific antigen levels	5.000000e-13
GCST003984_8	Parkinson’s disease	6.000000e-12
GCST004902_40	Parkinson’s disease	1.000000e-23
GCST004904_111	Body mass index	4.000000e-08
GCST006061_200	Atrial fibrillation	8.000000e-09
GCST006061_85	Atrial fibrillation	1.000000e-09
GCST006414_111	Atrial fibrillation	2.000000e-08
GCST006896_19	Free thyroxine concentration	6.000000e-08
GCST008152_171	Weight	7.000000e-06
GCST008152_176	Weight	8.000000e-06
GCST009325_31	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-29
GCST010241_77	Apolipoprotein A1 levels	1.000000e-13
GCST010242_334	HDL cholesterol levels	3.000000e-13
GCST010697_7	Cortical surface area (min-P)	8.000000e-11
GCST010698_41	Subcortical volume (min-P)	8.000000e-12
GCST010699_29	Brain morphology (min-P)	3.000000e-09
GCST010700_18	Cortical thickness (MOSTest)	5.000000e-12
GCST010701_13	Cortical surface area (MOSTest)	3.000000e-08
GCST010702_124	Subcortical volume (MOSTest)	3.000000e-09
GCST010703_107	Brain morphology (MOSTest)	2.000000e-20
GCST010991_25	Parkinson’s disease	4.000000e-11
GCST012004_4	Posterior thalamic nuclei volume	2.000000e-09
GCST90000025_843	Appendicular lean mass	7.000000e-33

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:0004338	body weight
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0006935	thalamus volume
EFO:0004980	appendicular lean mass
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	5
Cadmium Chloride	increases expression, decreases expression, increases abundance	4
bisphenol A	decreases expression, increases expression	3
Fluorouracil	decreases expression, affects reaction	3
arsenite	affects expression, affects binding, increases reaction	2
sodium arsenite	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Cadmium	increases abundance, increases expression, decreases expression	2
Cocaine	decreases expression	2
Doxorubicin	affects reaction, affects phosphorylation, affects response to substance, decreases expression, increases phosphorylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
salinomycin	decreases expression	1
trichostatin A	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
coumarin	affects phosphorylation	1
cupric oxide	decreases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3CY	Abcam HEK293T NUCKS1 KO	Transformed cell line	Female
CVCL_W802	PC-53	Cancer cell line	Female

Clinical trials (associated diseases)

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