ONECUT1

Chr 15

one cut homeobox 1

Also known as: HNF-6, HNF6, HNF6A

NCBI Gene: 3175 ENSG00000169856 UniProt: Q9UBC0

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. [provided by RefSeq, Dec 2012]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.59

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.523

Z-score 2.45

OE 0.19 (0.08–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.52Z-score

OE missense 0.91 (0.82–1.01)

237 obs / 260.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.08–0.59)

0≤0.351.4

Missense OE?0.91 (0.82–1.01)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 2 / 10.6Missense obs/exp: 237 / 260.8Syn Z: -0.36

Background carrier burden — how many people carry a rare variant somewhere in ONECUT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

681 rare PASS variants

Rare truncating (LoF)

1 in 11,000

34 rare PASS variants

Rare synonymous (reference)

1 in 240

304 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ONECUT1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 14,000
South Asian	~43k	1 in 110	≈ 1 in 40,000
Remaining (unassigned)	~30k	1 in 97	≈ 1 in 15,000
European (Finnish)	~27k	1 in 180	1 in 2,800
Admixed American	~22k	1 in 100	none seen
African / African American	~21k	1 in 120	1 in 3,100
East Asian	~20k	1 in 88	none seen
Ashkenazi Jewish	~13k	1 in 210	none seen
Middle Eastern	~2,884	1 in 79	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.