ONECUT1

Summary

ONECUT1 (one cut homeobox 1, HGNC:8138) is a protein-coding gene on chromosome 15q21.3, encoding Hepatocyte nuclear factor 6 (Q9UBC0). Transcriptional activator.

This gene encodes a member of the Cut homeobox family of transcription factors. Expression of the encoded protein is enriched in the liver, where it stimulates transcription of liver-expressed genes, and antagonizes glucocorticoid-stimulated gene transcription. This gene may influence a variety of cellular processes including glucose metabolism, cell cycle regulation, and it may also be associated with cancer. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3175 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neonatal diabetes mellitus (Strong, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 62 total
• Phenotypes (HPO): 1
• Transcription factor: yes — 38 downstream targets (CollecTRI)
• MANE Select transcript: NM_004498

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8138
Approved symbol	ONECUT1
Name	one cut homeobox 1
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	HNF-6
Ensembl gene	ENSG00000169856
Ensembl biotype	protein_coding
OMIM	604164
Entrez	3175

Gene structure

Transcript identifiers

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

ENST00000305901, ENST00000560699, ENST00000561401, ENST00000570208

RefSeq mRNA: 1 — MANE Select: NM_004498 NM_004498

CCDS: CCDS10150

Canonical transcript exons

ENST00000305901 — 2 exons

Exon	Start	End
ENSE00001125651	52755053	52757847
ENSE00001224516	52788780	52790336

Expression profiles

Bgee: expression breadth broad, 56 present calls, max score 86.48.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1569 / max 151.9046, expressed in 247 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150046	0.9704	210
150047	0.0807	35
150044	0.0559	25
150048	0.0297	14
150045	0.0201	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	86.48	gold quality
right lobe of liver	UBERON:0001114	85.18	gold quality
gall bladder	UBERON:0002110	82.63	gold quality
pancreas	UBERON:0001264	82.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.80	gold quality
islet of Langerhans	UBERON:0000006	77.92	gold quality
buccal mucosa cell	CL:0002336	77.63	silver quality
liver	UBERON:0002107	76.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.70	gold quality
pancreatic ductal cell	CL:0002079	69.46	silver quality
right testis	UBERON:0004534	68.60	gold quality
left testis	UBERON:0004533	66.95	gold quality
testis	UBERON:0000473	64.71	gold quality
endometrium epithelium	UBERON:0004811	60.95	gold quality
diaphragm	UBERON:0001103	60.53	gold quality
mucosa of paranasal sinus	UBERON:0005030	54.12	gold quality
quadriceps femoris	UBERON:0001377	53.20	gold quality
epithelial cell of pancreas	CL:0000083	52.84	gold quality
vastus lateralis	UBERON:0001379	52.53	gold quality
Brodmann (1909) area 10	UBERON:0013541	52.12	gold quality
tibialis anterior	UBERON:0001385	51.67	silver quality
ileal mucosa	UBERON:0000331	51.25	silver quality
cerebellar vermis	UBERON:0004720	50.92	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
bone marrow cell	CL:0002092	49.73	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
thymus	UBERON:0002370	49.27	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	1565.11
E-GEOD-137537	yes	1434.48
E-MTAB-8495	yes	473.07
E-MTAB-6911	yes	251.27
E-MTAB-10553	yes	19.07
E-GEOD-83139	yes	10.81
E-ANND-3	yes	4.80

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

38 targets.

Target	Regulation
ABCC2
AFP	Unknown
ALB
CCN2	Repression
CCND1	Repression
CREBBP
CYP3A4
CYP51A1
FOXA1	Unknown
FOXA2
G6PC1
GCK
GH1
HNF1B
HNF4A
HSPH1
INS	Unknown
LCT
MAFA
MIR122
MITF	Unknown
MMP7	Activation
NEUROG3	Unknown
NUPR1	Activation
ONECUT1
ONECUT3	Unknown
PCK1
PDX1
PROC	Activation
S100A8

JASPAR motifs

Motif	Name	Family
MA0679.1	ONECUT1	HD-CUT
MA0679.2	ONECUT1	HD-CUT
MA0679.3	ONECUT1	HD-CUT

JASPAR matrix evidence (PMIDs): PMID:8887657

Upstream regulators (CollecTRI, top): CEBPA, EZH2, FOXA2, FOXM1, HNF1B, HNF4A, ONECUT1, ONECUT3, STAT5A, TBX3

miRNA regulators (miRDB)

30 targeting ONECUT1, 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-9-5P	100.00	72.28	2361
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-657	99.48	66.02	848
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-219B-5P	97.91	65.80	531
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-1278	97.75	67.55	628
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-7703	97.64	67.00	965
HSA-MIR-610	96.84	67.98	905
HSA-MIR-490-5P	96.75	65.81	661
HSA-MIR-4529-3P	96.40	66.46	582
HSA-MIR-549A-5P	96.35	68.08	587
HSA-MIR-431-5P	96.16	66.50	652
HSA-MIR-3622B-5P	94.62	64.58	835

Literature-anchored findings (GeneRIF, showing 22)

• HNF6 has a role as a coactivator protein to potentiate the transcriptional activity of another liver factor, FoxA2 (PMID:12509444)
• These findings define a precursor cellular stage of the embryonic pancreas and place Hnf1beta in a genetic hierarchy that regulates the generation of pancreatic endocrine cells. (PMID:14570708)
• identifed systematically the genes occupied by the transcriptional regulators HNF1alpha, HNF4alpha, and HNF6, together with RNA polymerase II in human liver and pancreatic islets (PMID:14988562)
• HNF6 protein stability is controlled by CBP acetylation (PMID:15304484)
• A comparision of gene expression patterns induced by hepatic nuclear factors, HNF6, HNF4alpha and HNF1beta, in a pancreatic beta-cell line. (PMID:15520459)
• HNF6 DNA binding is selectively abrogated through lack of post-translational modification and interaction with FOXA2. Targeting of FOXA2 and HNF6 may therefore enable mechanism-based therapy for colorectal liver metastases (PMID:17283222)
• ONECUT1 expression is lost in pancreatic cancer cells, suggesting a tumor suppressor function in this malignancy. (PMID:18097590)
• Results suggest that HNF-6 is a novel target of small heterodimer partner in the regulation of gluconeogenesis. (PMID:18459945)
• functional knockdown of FOXA2 recovered HNF6 activity and inhibited growth of tumor-cells and may possibly represent a novel therapeutic target in primary and secondary liver malignancies (PMID:20967225)
• Hepatocyte nuclear factor 6 is one of the liver-enriched transcription factors, it utilizes the bipartite onecut-homeodomain sequence to localize to the nuclear compartment and bind specific DNA sequences of numerous target gene promoters (PMID:21893194)
• HNF6 and Sox9 are new biomarkers of pancreatic acinar-to-ductal metaplasia and constitute candidate targets for preventive treatment in cases when acinar-to-ductal metaplasia may lead to cancer. (PMID:22271799)
• HNF6 plays an important role in the gene regulation of CYP3A4 during development from the fetal period to the postnatal period. (PMID:23291635)
• Mutations at the -5/-6 site of the F9 promotor account for the majority of hemophilia B Leyden cases and disrupt the binding of ONECUT1 and ONECUT2. (PMID:23472758)
• HNF6 inhibits EMT, cell migration, and invasive growth through a mechanism involving the transcriptional activation of p53. (PMID:24022481)
• The negative correlation between HNF6 expression and pancreatic cancer progression suggests that HNF6 maintains pancreatic epithelial homeostasis, and that its loss contributes to the progression from intraepithelial neoplasms to ductal adenocarcinoma. (PMID:24638272)
• HNF6 is a novel host factor that can restrict hepatitis B virus replication via both transcriptional and posttranscriptional mechanisms. (PMID:25653429)
• Reduced HNF6 expression is associated with metastasis of cholangiocarcinoma. (PMID:26825606)
• HNF6 promoted colorectal cancer cell proliferation and tumor growth, and may contribute to liver metastasis via conferring cell resistance to anoikis. (PMID:30256389)
• Data show that chromatin regions that contain the ONECUT motif were in- or lowly accessible in fibroblasts and became accessible after the overexpression of ONECUT1, ONECUT2 or ONECUT3. (PMID:31049588)
• Mutations and variants of ONECUT1 in diabetes. (PMID:34663987)
• Transcriptional changes and the role of ONECUT1 in hPSC pancreatic differentiation. (PMID:34789845)
• Contribution of ONECUT1 variants to different forms of non-autoimmune diabetes mellitus in Italian patients. (PMID:35482136)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	onecut1	ENSDARG00000007982
mus_musculus	Onecut1	ENSMUSG00000043013
rattus_norvegicus	Onecut1	ENSRNOG00000008095
drosophila_melanogaster	onecut	FBGN0028996
caenorhabditis_elegans		WBGENE00000444
caenorhabditis_elegans		WBGENE00000459
caenorhabditis_elegans		WBGENE00000460
caenorhabditis_elegans		WBGENE00015934
caenorhabditis_elegans		WBGENE00017538

Paralogs (2): ONECUT2 (ENSG00000119547), ONECUT3 (ENSG00000205922)

Protein

Protein identifiers

Hepatocyte nuclear factor 6 — Q9UBC0 (reviewed: Q9UBC0)

Alternative names: One cut domain family member 1, One cut homeobox 1

All UniProt accessions (2): Q9UBC0, U3KQR8

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator. Binds the consensus sequence 5’-DHWATTGAYTWWD-3’ on a variety of gene promoters such as those of HNF3B and TTR. Important for liver genes transcription.

Subunit / interactions. Binds DNA as a monomer.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in liver; lower expression in testis and skin.

Similarity. Belongs to the CUT homeobox family.

RefSeq proteins (1): NP_004489* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR003350	CUT_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR010982	Lambda_DNA-bd_dom_sf	Homologous_superfamily
IPR051649	CUT_Homeobox	Family

Pfam: PF00046, PF02376

UniProt features (16 total): sequence conflict 5, region of interest 4, compositionally biased region 3, DNA-binding region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBC0-F1	60.78	0.28

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-210744	Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells
R-HSA-210747	Regulation of gene expression in early pancreatic precursor cells
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells
R-HSA-9937080	Developmental Lineage of Multipotent Pancreatic Progenitor Cells

MSigDB gene sets: 180 (showing top): GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GRUETZMANN_PANCREATIC_CANCER_DN, E2F4DP1_01, GOBP_B_CELL_ACTIVATION, GOBP_EPITHELIAL_CELL_DEVELOPMENT, TAL1ALPHAE47_01, SP1_Q2_01, GOBP_PANCREAS_DEVELOPMENT, PATIL_LIVER_CANCER, E2F_Q3, UEDA_PERIFERAL_CLOCK, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY

GO Biological Process (24): liver development (GO:0001889), regulation of cell-matrix adhesion (GO:0001952), epithelial cell development (GO:0002064), type B pancreatic cell differentiation (GO:0003309), pancreatic A cell differentiation (GO:0003310), pancreatic D cell differentiation (GO:0003311), glucose metabolic process (GO:0006006), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transforming growth factor beta receptor signaling pathway (GO:0007179), Notch signaling pathway (GO:0007219), endoderm development (GO:0007492), anatomical structure morphogenesis (GO:0009653), cell migration (GO:0016477), B cell differentiation (GO:0030183), positive regulation of cell migration (GO:0030335), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), cell fate commitment (GO:0045165), positive regulation of transcription by RNA polymerase II (GO:0045944), spleen development (GO:0048536), cilium assembly (GO:0060271), pancreas development (GO:0031016), endocrine pancreas development (GO:0031018), enteroendocrine cell differentiation (GO:0035883)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Cell Lineages of the Exocrine Pancreas	3
Regulation of beta-cell development	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endocrine pancreas development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
enteroendocrine cell differentiation	2
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
gland development	1
hepaticobiliary system development	1
cell-matrix adhesion	1
regulation of cell-substrate adhesion	1
epithelial cell differentiation	1
cell development	1
intestinal type D enteroendocrine cell differentiation	1
hexose metabolic process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell surface receptor signaling pathway	1
tissue development	1
developmental process	1
anatomical structure development	1
cell motility	1
lymphocyte differentiation	1
B cell activation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
cell differentiation	1
cellular developmental process	1
positive regulation of DNA-templated transcription	1
hematopoietic or lymphoid organ development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1

Protein interactions and networks

STRING

1360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ONECUT1	FOXA2	Q9Y261	948
ONECUT1	HNF1A	P20823	914
ONECUT1	NEUROG3	Q9Y4Z2	874
ONECUT1	HNF4A	P41235	855
ONECUT1	FOXA1	P55317	846
ONECUT1	HNF1B	P35680	827
ONECUT1	NR1D1	P20393	797
ONECUT1	PROX1	Q92786	753
ONECUT1	SOX9	P48436	752
ONECUT1	CEBPA	P49715	725
ONECUT1	PDX1	P52945	720
ONECUT1	HHEX	Q03014	718
ONECUT1	RFX6	Q8HWS3	707
ONECUT1	PTF1A	Q7RTS3	705
ONECUT1	FOXM1	Q08050	704

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ONECUT1	SERPINB13	psi-mi:“MI:0915”(physical association)	0.400
ONECUT1	CDS1	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): SERPINB13 (Affinity Capture-MS), ONECUT1 (Affinity Capture-MS), ONECUT1 (Reconstituted Complex), KAT2B (Reconstituted Complex), KAT2B (Phenotypic Enhancement), ONECUT1 (Reconstituted Complex), ONECUT1 (Reconstituted Complex), ONECUT1 (Affinity Capture-Western), ONECUT1 (Affinity Capture-Western), SERPINB13 (Affinity Capture-MS), CDS1 (Affinity Capture-MS), ONECUT1 (Reconstituted Complex), ST6GALNAC1 (Cross-Linking-MS (XL-MS)), ONECUT1 (Co-fractionation), ONECUT1 (Co-fractionation)

ESM2 similar proteins: O08755, O16011, O43312, O60422, O77638, O88532, O88942, O95948, P0CL69, P17544, P54288, P70512, P98201, Q01826, Q02930, Q08289, Q08DV5, Q13469, Q3UR85, Q5R9C9, Q5REX3, Q5VTB9, Q60591, Q60611, Q6NT76, Q6P1E1, Q6P9S0, Q6PDX6, Q6UFS5, Q6UUV9, Q6XBJ3, Q765P7, Q7TMA2, Q8BIE6, Q8BJA3, Q8C0V0, Q8CIE2, Q8HXD5, Q8K557, Q8NF64

Diamond homologs: O08755, O14529, O60422, O95948, P70298, P70512, Q04650, Q19720, Q22811, Q22812, Q6XBJ3, Q8K557, Q8TE12, Q9BL02, Q9JKU8, Q9NJB5, Q9UBC0, P34237, P39880, P39881, P53564, P53565, P70403, Q13948, Q5R8V1, P10180, O42115, Q8IA98

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

612 predictions. Top by Δscore:

Variant	Effect	Δscore
15:52757845:ATG:A	acceptor_gain	1.0000
15:52757846:TG:T	acceptor_gain	1.0000
15:52757847:GCTG:G	acceptor_loss	1.0000
15:52757848:C:CC	acceptor_gain	1.0000
15:52757849:T:G	acceptor_loss	1.0000
15:52757843:GCATG:G	acceptor_gain	0.9900
15:52757844:CATG:C	acceptor_gain	0.9900
15:52757844:CATGC:C	acceptor_gain	0.9900
15:52788775:CTCA:C	donor_loss	0.9900
15:52788776:TCA:T	donor_loss	0.9900
15:52788779:C:A	donor_loss	0.9900
15:52757850:G:GC	acceptor_gain	0.9800
15:52780594:G:A	donor_gain	0.9800
15:52780599:A:AC	donor_gain	0.9700
15:52788779:CCTG:C	donor_gain	0.9700
15:52757847:GCTGT:G	acceptor_gain	0.9500
15:52757850:G:C	acceptor_gain	0.9500
15:52788831:T:TA	donor_gain	0.9300
15:52757845:ATGCT:A	acceptor_gain	0.9200
15:52759363:ACTT:A	acceptor_gain	0.9200
15:52759364:CTTC:C	acceptor_gain	0.9200
15:52757848:CTGTG:C	acceptor_gain	0.9100
15:52759365:T:A	acceptor_gain	0.9100
15:52760212:C:CA	donor_gain	0.9100
15:52780591:A:AC	donor_gain	0.9000
15:52780619:C:CA	donor_gain	0.9000
15:52780897:A:C	acceptor_gain	0.9000
15:52788235:CT:C	donor_gain	0.8800
15:52757846:TGCT:T	acceptor_gain	0.8700
15:52757845:A:C	acceptor_gain	0.8500

AlphaMissense

3085 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:52757636:C:A	R439S	1.000
15:52757636:C:G	R439S	1.000
15:52757637:C:A	R439M	1.000
15:52757637:C:G	R439T	1.000
15:52757638:T:A	R439W	1.000
15:52757638:T:C	R439G	1.000
15:52757639:C:A	R438S	1.000
15:52757639:C:G	R438S	1.000
15:52757640:C:A	R438M	1.000
15:52757640:C:G	R438T	1.000
15:52757641:T:A	R438W	1.000
15:52757641:T:C	R438G	1.000
15:52757642:T:A	R437S	1.000
15:52757642:T:G	R437S	1.000
15:52757643:C:A	R437I	1.000
15:52757643:C:G	R437T	1.000
15:52757644:T:C	R437G	1.000
15:52757647:C:G	A436P	1.000
15:52757648:G:C	N435K	1.000
15:52757648:G:T	N435K	1.000
15:52757649:T:A	N435I	1.000
15:52757649:T:C	N435S	1.000
15:52757649:T:G	N435T	1.000
15:52757650:T:C	N435D	1.000
15:52757650:T:G	N435H	1.000
15:52757651:C:A	M434I	1.000
15:52757651:C:G	M434I	1.000
15:52757651:C:T	M434I	1.000
15:52757652:A:G	M434T	1.000
15:52757652:A:T	M434K	1.000

dbSNP variants (sampled 300 via entrez): RS1000109858 (15:52786965 A>G), RS1000335948 (15:52787651 G>A), RS1000368646 (15:52787768 G>T), RS1000405149 (15:52769435 C>A), RS1000448091 (15:52780979 C>T), RS1000584956 (15:52762523 T>C), RS1000597725 (15:52764541 T>A), RS1000684852 (15:52776771 T>A,G), RS1000830339 (15:52785611 C>A), RS1000858868 (15:52769070 A>T), RS1000979883 (15:52791647 C>G), RS1001061640 (15:52779335 G>A), RS1001149496 (15:52758194 C>A), RS1001199170 (15:52755474 A>C), RS1001261183 (15:52757227 T>C)

Disease associations

OMIM: gene MIM:604164 | disease phenotypes: MIM:174050

GenCC curated gene-disease

Disease	Classification	Inheritance
neonatal diabetes mellitus	Strong	Autosomal recessive

Mondo (2): autosomal dominant polycystic liver disease (MONDO:0000447), neonatal diabetes mellitus (MONDO:0016391)

Orphanet (1): Isolated polycystic liver disease (Orphanet:2924)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0006557	Polycystic liver disease

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002935_25	Lead levels	9.000000e-06
GCST005143_4	Telomere length	4.000000e-06
GCST007576_255	Chronotype	5.000000e-11
GCST007615_39	C-reactive protein levels	7.000000e-09
GCST007615_4	C-reactive protein levels	4.000000e-09
GCST008362_55	Birth weight	4.000000e-08
GCST009379_201	Type 2 diabetes	5.000000e-09
GCST009391_848	Metabolite levels	7.000000e-06
GCST010988_552	Adult body size	5.000000e-08
GCST010988_553	Adult body size	3.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0004458	C-reactive protein measurement
EFO:0004344	birth weight
EFO:0010400	triacylglycerol 46:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	3
Cyclosporine	decreases expression	3
Acetaminophen	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
deguelin	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrimidifen	decreases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
picoxystrobin	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Antimycin A	decreases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Tretinoin	affects expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Serpentine	decreases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1
Palmitic Acid	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4Z9	SEES3-1V human ONECUT1, clone1	Embryonic stem cell	Male
CVCL_A5A0	SEES3-1V human ONECUT1, clone2	Embryonic stem cell	Male
CVCL_A5A1	SEES3-1V human ONECUT1, clone3	Embryonic stem cell	Male
CVCL_D3XF	HepG2/8F_HS	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01157858	PHASE2	COMPLETED	Everolimus and LongActing Octreotide Trial in Polycystic Livers
NCT01670110	PHASE2	COMPLETED	Pasireotide LAR in Severe Polycystic Liver Disease
NCT02021110	PHASE2	COMPLETED	Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease
NCT05478083	PHASE2	RECRUITING	A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
NCT00426153	PHASE2/PHASE3	COMPLETED	Octreotide in Severe Polycystic Liver Disease
NCT00565097	PHASE2/PHASE3	COMPLETED	Lanreotide as Treatment of Polycystic Livers
NCT00771888	PHASE2/PHASE3	UNKNOWN	Open-Label Extension of LOCKCYST Trial
NCT01315795	PHASE2/PHASE3	COMPLETED	Lanreotide Autogel in the Treatment of Symptomatic Polycystic Liver Disease
NCT05281328	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With PLD
NCT00934791	Not specified	TERMINATED	Polycystic Liver Disease in Kidney Transplant
NCT01354405	Not specified	COMPLETED	Somatostatin Analogues as a Volume Reducing Treatment of Polycystic Livers (RESOLVE)
NCT02173080	Not specified	COMPLETED	Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).
NCT03960710	Not specified	UNKNOWN	Automatic Segmentation of Polycystic Liver
NCT04111692	Not specified	RECRUITING	A Prospective Observational Study of Foam Sclerotherapy .
NCT04645251	Not specified	RECRUITING	Polycystic Liver Disease Registry (UK)
NCT05215964	Not specified	UNKNOWN	The Association Between Skeletal Muscle Mass and Severity of Polycystic Liver Disease and Polycystic Kidney Disease
NCT05500157	Not specified	UNKNOWN	Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts