ONECUT2

protein-coding

one cut homeobox 2, the group of CUT class homeoboxes and pseudogenes

Gene summary

This gene encodes a member of the onecut family of transcription factors, which are characterized by a cut domain and an atypical homeodomain. The protein binds to specific DNA sequences and stimulates expression of target genes, including genes involved in melanocyte and hepatocyte differentiation. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004852.3

Inheritance

—

ClinVar variants

U:73B:6

Top phenotype

Autosomal dominant polycystic liver disease

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr18:57,435,374-57,491,298

External References & Databases

Ensembl (ENSG00000119547)

Transcript & Mutation Effects

hg38 • Region Span ~55.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ONECUT2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 5

Autosomal dominant polycystic liver diseaseTotal: 3

Autosomal dominant polycystic kidney diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004852.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	2 clinvar	5
missense			73 clinvar	1 clinvar		74
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	73	4	2	79

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004852.3	RefSeq	NP_004843.2	2	MANE Select
ENST00000491143.3	Ensembl	ENSP00000419185.2	2	MANE Select
XM_047437945.1	RefSeq	XP_047293901.1	2	Standard
XM_047437946.1	RefSeq	XP_047293902.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

liver development
regulation of cell-matrix adhesion
epithelial cell development
animal organ morphogenesis
cell differentiation

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA binding

Cellular Component

nucleus
nucleoplasm
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000491143
Coding exons: 2
Length: 55613
Individuals with no LoFs: 124347
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 124348
p: 0.00000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.32	219	281	0.779	0.0000147	3248
Missense (PolyPhen)		87	111.01	0.7837		1150
Synonymous	-1.02	133	119	1.12	0.00000608	1058
Loss of Function	2.95	1	12.1	0.0830	6.06e-7	127

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000089	0.0000089	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional activator. Activates the transcription of a number of liver genes such as HNF3B.;

Recessive Scores

pRec: 0.184

Intolerance Scores

LoFtool: 0.0369
RVIS EVS: -0.6
RVIS percentile EVS: 17.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.991

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium