ONECUT2

Chr 18

one cut homeobox 2

Also known as: OC-2, OC2

The protein is a transcription factor that binds specific DNA sequences and activates expression of target genes involved in liver development and melanocyte differentiation. Mutations cause autosomal dominant or recessive neurodevelopmental disorders with intellectual disability, often accompanied by seizures and brain malformations. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein disruption.

Summary from RefSeq, UniProt
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0
Active trials
17
Pubs (1 yr)
66
P/LP submissions
0%
P/LP missense
0.39
LOEUF
LOF
Mechanism· predicted
Clinical SummaryONECUT2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
64 unique Pathogenic / Likely Pathogenic· 77 VUS of 151 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.39LOEUF
pLI 0.907
Z-score 2.95
OE 0.08 (0.030.39)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.32Z-score
OE missense 0.78 (0.700.87)
219 obs / 281.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.030.39)
00.351.4
Missense OE0.78 (0.700.87)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 1 / 12.1Missense obs/exp: 219 / 281.2Syn Z: -1.02
DN
0.4388th %ile
GOF
0.2895th %ile
LOF
0.86top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.39

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

151 submitted variants in ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic2
VUS77
Likely Benign4
Benign2
62
Pathogenic
2
Likely Pathogenic
77
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
2
0
2
VUS
0
72
5
0
77
Likely Benign
0
1
0
3
4
Benign
0
0
0
2
2
Total073695147

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ONECUT2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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