NOLC1

Summary

NOLC1 (nucleolar and coiled-body phosphoprotein 1, HGNC:15608) is a protein-coding gene on chromosome 10q24.32, encoding Nucleolar and coiled-body phosphoprotein 1 (Q14978). Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification. It is a selective cancer dependency (DepMap: 61.3% of cell lines).

Enables molecular function inhibitor activity; protein heterodimerization activity; and protein-macromolecule adaptor activity. Involved in neural crest cell development; neural crest formation; and regulation of translation. Acts upstream of or within axonogenesis and regulation of synaptic plasticity. Located in fibrillar center.

Source: NCBI Gene 9221 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 137 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 61.3% of screened cell lines
• MANE Select transcript: NM_004741

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15608
Approved symbol	NOLC1
Name	nucleolar and coiled-body phosphoprotein 1
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	P130, KIAA0035, NOPP140, NOPP130, Srp40
Ensembl gene	ENSG00000166197
Ensembl biotype	protein_coding
OMIM	602394
Entrez	9221

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 29 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000370007, ENST00000405356, ENST00000461421, ENST00000464969, ENST00000476468, ENST00000477977, ENST00000488254, ENST00000603946, ENST00000605788, ENST00000879605, ENST00000879606, ENST00000879607, ENST00000879608, ENST00000879609, ENST00000879610, ENST00000879611, ENST00000879612, ENST00000879613, ENST00000915036, ENST00000915037, ENST00000915038, ENST00000915039, ENST00000915040, ENST00000915041, ENST00000915042, ENST00000915043, ENST00000915044, ENST00000915045, ENST00000915046, ENST00000915047, ENST00000949543, ENST00000949544

RefSeq mRNA: 3 — MANE Select: NM_004741 NM_001284388, NM_001284389, NM_004741

CCDS: CCDS65925, CCDS65926, CCDS7530

Canonical transcript exons

ENST00000605788 — 13 exons

Exon	Start	End
ENSE00000000208	102152389	102152530
ENSE00003487441	102159193	102159308
ENSE00003506285	102159433	102159568
ENSE00003526135	102160233	102160343
ENSE00003537554	102160452	102161093
ENSE00003547298	102157189	102157328
ENSE00003549288	102161556	102161662
ENSE00003601093	102159896	102160024
ENSE00003623059	102158049	102158214
ENSE00003633820	102157019	102157074
ENSE00003659529	102161833	102161925
ENSE00003676659	102157431	102157555
ENSE00003903974	102162111	102163870

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.0954 / max 578.9577, expressed in 1821 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106685	71.9011	1821
106683	0.6954	380
106688	0.3333	134
106684	0.1656	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.03	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.72	gold quality
germinal epithelium of ovary	UBERON:0001304	97.79	gold quality
parietal pleura	UBERON:0002400	97.72	gold quality
cervix squamous epithelium	UBERON:0006922	97.72	gold quality
gingival epithelium	UBERON:0001949	97.58	gold quality
epithelium of nasopharynx	UBERON:0001951	97.53	gold quality
endothelial cell	CL:0000115	97.51	gold quality
epithelial cell of pancreas	CL:0000083	97.48	gold quality
squamous epithelium	UBERON:0006914	97.45	gold quality
pleura	UBERON:0000977	97.38	gold quality
esophagus squamous epithelium	UBERON:0006920	97.29	gold quality
gingiva	UBERON:0001828	97.24	gold quality
visceral pleura	UBERON:0002401	97.20	gold quality
sperm	CL:0000019	96.50	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.27	gold quality
tibia	UBERON:0000979	96.16	gold quality
epithelium of esophagus	UBERON:0001976	95.98	gold quality
male germ cell	CL:0000015	95.96	gold quality
amniotic fluid	UBERON:0000173	95.89	gold quality
cartilage tissue	UBERON:0002418	95.84	gold quality
colonic mucosa	UBERON:0000317	95.42	gold quality
oral cavity	UBERON:0000167	95.41	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.32	gold quality
superficial temporal artery	UBERON:0001614	95.19	gold quality
mammalian vulva	UBERON:0000997	95.16	gold quality
cauda epididymis	UBERON:0004360	95.16	gold quality
entorhinal cortex	UBERON:0002728	95.14	gold quality
type B pancreatic cell	CL:0000169	95.06	gold quality
corpus epididymis	UBERON:0004359	94.96	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	619.97
E-CURD-112	yes	8.62
E-MTAB-9689	no	453.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, NFKB1, NFKB, RELA

miRNA regulators (miRDB)

51 targeting NOLC1, 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-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-10399-5P	99.17	69.87	2610

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 61.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 27)

• NOPP140 is involved in a PKA signaling pathway that leads to agp activation (PMID:12167624)
• These data show that Nopp140 reversibly associates with snoRNPs in a phosphorylation-dependent manner, but this association has no effect on pseudouridylation of rRNA. (PMID:12446766)
• Hypoxia induces substantial p130 dephosphorylation and nuclear accumulation, leading to the formation of E2F4/p130 complexes and increased occupancy of E2F4 and p130 at the RAD51 and BRCA1 promoters. (PMID:17001309)
• hNopp140 serves as a negative regulator of CK2 and InsP(6) stimulates the activity of CK2 by blocking the interaction between hNopp140 and CK2 (PMID:17038328)
• Evolutionarily conserved multisubunit protein complex that contains p130 and E2F4 mediates the repression of cell cycle-dependent genes in quiescence. (PMID:17531812)
• hNopp140, a scaffold protein, is involved in the nucleolar assembly, fusion, and maintenance (PMID:18253863)
• InsP(6) specifically binds to CK2alpha and disrupts the interaction between CK2alpha and Nopp140 with an IC(50) value of 25 microM, thereby attenuating the Nopp140-mediated repression of CK2 activity. (PMID:18790693)
• The functional deficiency in spinal muscular atrophy cells is associated with decreased localization of the snoRNP chaperone Nopp140 in Cajal bodies that correlates with disease severity. (PMID:19129172)
• Nopp140 could be a component implicated in the early steps of pre-rRNA processing. (PMID:19381672)
• both NOLC1 and tumor protein 53 work together synergistically to activate the MDM2 promoter in NPC cells. (PMID:19541936)
• The regulation of NOCL1 protein is a critical role for the transcription NF-kB and cAMP response element-bing protein (PMID:21266110)
• Structural disorder and local order of hNopp140 (PMID:22906532)
• H5N1 viral NS1 interacts with host NOLC1 protein. (PMID:23188192)
• our study demonstrated that DNA methylation is a key mechanism of silenced NOLC1 expression in human hepatocellular carcinoma cells, and NOLC1 gene hypermethylation of the four CpG dinucleotides is a potential biomarker for hepatocellular carcinoma. (PMID:23970161)
• A Nopp140 fragment (residues 568-596) and inositol hexakisphosphate competitively bind to the catalytic subunit of CK2 (CK2alpha), and phospho-Ser574 of Nopp140 significantly enhances its interaction with CK2alpha. (PMID:24218616)
• pRb2/p130 cytoplasmic delocalization can lead to cell cycle deregulation (PMID:25205458)
• D120 and R195 of H5N1 influenza virus NS1 were crucial for the binding to host NOLC1. (PMID:25645906)
• In this study, the disordered feature of Nopp140 and the effect of CK2alpha on the structure of Nopp140 were examined using single-molecule fluorescence resonance energy transfer (smFRET) and electron paramagnetic resonance (EPR). (PMID:27297113)
• Nucleolar TRF2 attenuated nucleolus stress-induced hepatocellular carcinoma cell-cycle arrest by altering rRNA synthesis via interaction with NOLC1. (PMID:29725012)
• Identification and validation of NOLC1 might be a promising therapeutic strategy for the management of multidrug resistance of non-small cell lung cancer patients. (PMID:30505321)
• This study suggests that the dynamic distribution of telomerase between Cajal bodies and nucleoplasm uniquely impacts telomere length maintenance and identifies Nopp140 as a novel player in telomere biology. (PMID:31664887)
• Pten-NOLC1 fusion promotes cancers involving MET and EGFR signalings. (PMID:33323972)
• NOLC1 knockdown suppresses prostate cancer progressions by reducing AKT phosphorylation and beta-catenin accumulation. (PMID:36265288)
• Roles of NOLC1 in cancers and viral infection. (PMID:37296317)
• High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer. (PMID:37670166)
• T7 phage display reveals NOLC1 as a GM3 binding partner in human breast cancer MCF-7 cells. (PMID:37939867)
• Effects of the Nonstructural Protein-Nucleolar and Coiled-Body Phosphoprotein 1 Protein Interaction on rRNA Synthesis Through Telomeric Repeat-Binding Factor 2 Regulation Under Nucleolar Stress. (PMID:38062753)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nolc1	ENSDARG00000024561
mus_musculus	Nolc1	ENSMUSG00000015176
rattus_norvegicus	Nolc1	ENSRNOG00000018704
caenorhabditis_elegans	dao-5	WBGENE00000931

Protein

Protein identifiers

Nucleolar and coiled-body phosphoprotein 1 — Q14978 (reviewed: Q14978)

Alternative names: 140 kDa nucleolar phosphoprotein, Hepatitis C virus NS5A-transactivated protein 13, Nucleolar 130 kDa protein, Nucleolar phosphoprotein p130

All UniProt accessions (6): A0A0A0MRM9, Q14978, S4R341, S4R349, S4R3C2, S4R402

UniProt curated annotations — full annotation on UniProt →

Function. Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification. Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with TCOF1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification. Involved in nucleologenesis, possibly by playing a role in the maintenance of the fundamental structure of the fibrillar center and dense fibrillar component in the nucleolus. It has intrinsic GTPase and ATPase activities.

Subunit / interactions. Heterodimer; heterodimerizes with TCOF1 following monoubiquitination. Interacts with RNA polymerase I 194 kDa subunit (RPA194) and with casein kinase-II. Interacts with DKC1/NAP57, NOP58 and fibrillarin.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Post-translational modifications. Undergoes rapid and massive phosphorylation/dephosphorylation cycles on CK2 and PKC sites. NOLC1 is one of the mostly phosphorylated proteins in the cell. Ubiquitinated. Monoubiquitination by the BCR(KBTBD8) complex promotes the formation of a NOLC1-TCOF1 complex that acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification. Pyrophosphorylated by 5-diphosphoinositol pentakisphosphate (5-IP7). Serine pyrophosphorylation is achieved by Mg(2+)-dependent, but enzyme independent transfer of a beta-phosphate from a inositol pyrophosphate to a pre-phosphorylated serine residue.

Similarity. Belongs to the NOLC1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14978-1	Alpha	yes
Q14978-2	Beta
Q14978-3	3

RefSeq proteins (3): NP_001271317, NP_001271318, NP_004732* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006594	LisH	Conserved_site
IPR007718	Srp40_C	Domain
IPR039191	Nopp140-like	Family

Pfam: PF05022

UniProt features (84 total): modified residue 25, cross-link 22, compositionally biased region 14, repeat 11, region of interest 3, sequence conflict 3, splice variant 2, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14978-F1	54.48	0.12

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 (47): 33, 87, 90, 91, 91, 188, 362, 363, 366, 397, 415, 456, 508, 538, 563, 580, 582, 607, 610, 622 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 313 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, E2F_Q4, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_52, GOBP_RIBOSOME_BIOGENESIS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, E2F4DP1_01, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, MODULE_16, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

GO Biological Process (6): mitotic cell cycle (GO:0000278), rRNA processing (GO:0006364), regulation of translation (GO:0006417), nucleolus organization (GO:0007000), neural crest formation (GO:0014029), neural crest cell development (GO:0014032)

GO Molecular Function (9): RNA binding (GO:0003723), protein kinase inhibitor activity (GO:0004860), ATP binding (GO:0005524), GTP binding (GO:0005525), protein-macromolecule adaptor activity (GO:0030674), protein heterodimerization activity (GO:0046982), molecular function inhibitor activity (GO:0140678), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Cajal body (GO:0015030), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
purine ribonucleoside triphosphate binding	2
nuclear lumen	2
cell cycle	1
mitotic nuclear division	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nucleus organization	1
epithelial to mesenchymal transition	1
chordate embryonic development	1
anatomical structure formation involved in morphogenesis	1
neural crest cell differentiation	1
stem cell development	1
nucleic acid binding	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
adenyl ribonucleotide binding	1
guanyl ribonucleotide binding	1
protein binding	1
molecular adaptor activity	1
protein dimerization activity	1
molecular function regulator activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
nucleolus	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2852 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOLC1	COIL	P38432	962
NOLC1	FBL	P22087	955
NOLC1	DKC1	O60832	910
NOLC1	POLR1A	O95602	863
NOLC1	PHAX	Q9H814	846
NOLC1	NOP56	O00567	797
NOLC1	NUCLEOLIN	P19338	785
NOLC1	MKLN1	Q9UL63	766
NOLC1	OFD1	O75665	712
NOLC1	UBTF	P17480	670
NOLC1	TBL1X	O60907	663
NOLC1	KBTBD8	Q8NFY9	636
NOLC1	TCOF1	Q13428	625
NOLC1	NKTR	P30414	600
NOLC1	SUCLG2	Q96I99	586

IntAct

187 interactions, top by confidence:

A	B	Type	Score
YWHAG	NOLC1	psi-mi:“MI:0915”(physical association)	0.830
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
ARRB2	NOLC1	psi-mi:“MI:0915”(physical association)	0.760
RAB11FIP1	YWHAH	psi-mi:“MI:0914”(association)	0.740
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
PTK2	TGFB1I1	psi-mi:“MI:0914”(association)	0.680
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
NOP56	RPL7A	psi-mi:“MI:0914”(association)	0.640
CSNK2A2	PES1	psi-mi:“MI:0914”(association)	0.640
FGF12	TCOF1	psi-mi:“MI:0914”(association)	0.610
NOLC1	FGF12	psi-mi:“MI:0403”(colocalization)	0.590
NOLC1	FGF12	psi-mi:“MI:2364”(proximity)	0.590
NOLC1	FGF12	psi-mi:“MI:0914”(association)	0.590
YWHAZ	NOLC1	psi-mi:“MI:0915”(physical association)	0.590
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAE	SRSF10	psi-mi:“MI:0914”(association)	0.560
RNPC3	NOLC1	psi-mi:“MI:0915”(physical association)	0.540
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
NAPA	NBAS	psi-mi:“MI:0914”(association)	0.530
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
FAM9A	AP3B1	psi-mi:“MI:0914”(association)	0.530

BioGRID (466): NOLC1 (Affinity Capture-RNA), NOLC1 (Affinity Capture-RNA), NOLC1 (Affinity Capture-MS), NOLC1 (Affinity Capture-MS), NOLC1 (Affinity Capture-MS), NOLC1 (Affinity Capture-MS), NOLC1 (Affinity Capture-MS), NOLC1 (Affinity Capture-MS), NOLC1 (Affinity Capture-MS), NOLC1 (Affinity Capture-MS), NOLC1 (Affinity Capture-MS), BRIX1 (Co-fractionation), NOLC1 (Co-fractionation), NOLC1 (Co-fractionation), NOLC1 (Co-fractionation)

ESM2 similar proteins: A1L2F3, E9Q5C9, O08784, O35691, O45181, P08855, P12036, P16039, P16884, P19246, P41777, Q03111, Q08DU9, Q0P678, Q14978, Q1PEP5, Q24595, Q29S11, Q32N87, Q3TEA8, Q3UMU9, Q52KI8, Q56WH4, Q58CQ0, Q5I034, Q5SSJ5, Q5UQ16, Q5UQA4, Q5XGC9, Q5XXA7, Q5ZJJ1, Q5ZM33, Q6P4K1, Q6P747, Q6TQE1, Q7XTT4, Q7Z4V5, Q80XU3, Q86VM9, Q8C551

Diamond homologs: E9Q5C9, P32583, P41777, Q14978, Q9P785, Q9XVS4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKACA	up-regulates	NOLC1	phosphorylation
PRKACA	“up-regulates activity”	NOLC1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 193 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	5	28.0×	8e-05
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	24.7×	9e-05
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	24.7×	9e-05
Activation of BH3-only proteins	5	18.2×	3e-04
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	6	13.3×	3e-04
Intrinsic Pathway for Apoptosis	6	12.9×	3e-04
RHO GTPases activate PKNs	5	11.7×	2e-03
Apoptosis	9	11.1×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein import into nucleus	11	9.5×	3e-05
mRNA splicing, via spliceosome	10	5.5×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	104
Likely benign	14
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1498 predictions. Top by Δscore:

Variant	Effect	Δscore
10:102152526:GAGCT:G	donor_gain	1.0000
10:102152528:GCT:G	donor_gain	1.0000
10:102152531:G:GG	donor_gain	1.0000
10:102157075:G:GG	donor_gain	1.0000
10:102157184:A:AG	acceptor_gain	1.0000
10:102157185:G:GA	acceptor_gain	1.0000
10:102157298:G:GT	donor_gain	1.0000
10:102157325:GCTG:G	donor_gain	1.0000
10:102157327:TGG:T	donor_loss	1.0000
10:102157329:G:GG	donor_gain	1.0000
10:102157426:TTCA:T	acceptor_loss	1.0000
10:102157429:A:AG	acceptor_gain	1.0000
10:102157429:A:AT	acceptor_loss	1.0000
10:102157429:AGCT:A	acceptor_gain	1.0000
10:102157430:G:GA	acceptor_gain	1.0000
10:102157430:GCT:G	acceptor_gain	1.0000
10:102157430:GCTG:G	acceptor_gain	1.0000
10:102157430:GCTGT:G	acceptor_gain	1.0000
10:102157529:G:GT	donor_gain	1.0000
10:102157551:TCCAG:T	donor_loss	1.0000
10:102157552:CCAG:C	donor_loss	1.0000
10:102157554:AGGTT:A	donor_loss	1.0000
10:102157555:GGT:G	donor_loss	1.0000
10:102157556:G:A	donor_loss	1.0000
10:102157557:T:A	donor_loss	1.0000
10:102157580:GGGTT:G	donor_gain	1.0000
10:102158044:A:AG	acceptor_gain	1.0000
10:102158045:A:G	acceptor_gain	1.0000
10:102158047:A:AG	acceptor_gain	1.0000
10:102158047:A:T	acceptor_loss	1.0000

AlphaMissense

4588 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:102162129:T:A	W654R	1.000
10:102162129:T:C	W654R	1.000
10:102162131:G:C	W654C	1.000
10:102162131:G:T	W654C	1.000
10:102162154:T:C	L662S	1.000
10:102162177:T:C	F670L	1.000
10:102162178:T:C	F670S	1.000
10:102162178:T:G	F670C	1.000
10:102162179:T:A	F670L	1.000
10:102162179:T:G	F670L	1.000
10:102162189:A:G	K674E	1.000
10:102162191:A:C	K674N	1.000
10:102162191:A:T	K674N	1.000
10:102162195:A:G	K676E	1.000
10:102162197:G:C	K676N	1.000
10:102162197:G:T	K676N	1.000
10:102162201:A:G	K678E	1.000
10:102162133:G:A	G655E	0.999
10:102162142:C:A	A658D	0.999
10:102162168:G:C	G667R	0.999
10:102162168:G:T	G667C	0.999
10:102162169:G:A	G667D	0.999
10:102162169:G:T	G667V	0.999
10:102162177:T:G	F670V	0.999
10:102162181:G:C	R671P	0.999
10:102162183:C:G	H672D	0.999
10:102162188:G:C	E673D	0.999
10:102162188:G:T	E673D	0.999
10:102162189:A:C	K674Q	0.999
10:102162203:G:C	K678N	0.999

dbSNP variants (sampled 300 via entrez): RS1000194324 (10:102150419 T>G), RS1000390197 (10:102162930 C>A,T), RS1000522434 (10:102155308 T>C), RS1000658253 (10:102155079 A>G), RS1000670984 (10:102161764 A>G), RS1000735418 (10:102163169 G>C,T), RS1001226171 (10:102151341 C>G), RS1001610999 (10:102157196 A>G), RS1001661884 (10:102163755 A>C,G), RS1001763049 (10:102154244 T>A), RS1001787218 (10:102160180 T>G), RS1001841799 (10:102162201 A>C), RS1001896154 (10:102155616 C>G,T), RS1001903140 (10:102163480 G>A), RS1001966767 (10:102155976 C>A,T)

Disease associations

OMIM: gene MIM:602394 | 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
GCST010244_382	Triglyceride levels	1.000000e-10
GCST011703_47	Smoking initiation	2.000000e-10
GCST90013406_124	Liver enzyme levels (alkaline phosphatase)	3.000000e-83

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0005670	smoking initiation
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724612 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.86	Kd	13.87	nM	CHEMBL3752910
7.86	ED50	13.87	nM	CHEMBL3752910
7.20	Kd	63	nM	MOLIBRESIB
7.10	IC50	80	nM	MOLIBRESIB
6.75	Kd	177.6	nM	CHEMBL5653589
6.75	ED50	177.6	nM	CHEMBL5653589

PubChem BioAssay actives

4 with measured affinity, of 11 total; 3 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148878: Binding affinity to human NOLC1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0139	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179110: Binding affinity against NOLC1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0630	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148878: Binding affinity to human NOLC1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1776	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases abundance	5
Tretinoin	affects cotreatment, increases expression, decreases expression	4
Benzo(a)pyrene	decreases methylation, increases expression	3
Estradiol	increases expression, increases reaction	3
bisphenol A	decreases expression	2
deoxynivalenol	increases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Doxorubicin	decreases expression, affects binding, affects reaction	2
Nickel	increases expression	2
Ozone	increases abundance, affects cotreatment, increases oxidation	2
Valproic Acid	increases expression, increases methylation	2
Cyclosporine	increases expression, increases methylation	2
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bis(tri-n-butyltin)oxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
afimoxifene	decreases reaction, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651920	Binding	Binding affinity to human NOLC1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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