CUX1

Chr 7AD

cut like homeobox 1

Also known as: CASP, CDP, CDP/Cut, CDP1, COY1, CUTL1, CUX, Clox

NCBI Gene: 1523ENSG00000257923UniProt: P39880OMIM: 116896

CUX1 encodes a transcription factor that controls neuronal differentiation, dendrite development, and synaptogenesis in the brain, particularly in cortical layers II-III. Mutations cause autosomal dominant neurodevelopmental disorder with developmental delay and variable motor or speech delays. The gene is highly constrained against loss-of-function variants, indicating that proper CUX1 function is critical for normal development.

OMIMResearchSummary from OMIM, UniProt
LOFmechanismADLOEUF 0.161 OMIM phenotype
Clinical Summary— CUX1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 7.25
OE 0.08 (0.04–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.75Z-score
OE missense 0.64 (0.59–0.69)
543 obs / 850.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.08 (0.04–0.16)
0≤0.351.4
Missense OE0.64 (0.59–0.69)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 6 / 72.7Missense obs/exp: 543 / 850.7Syn Z: -0.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateCUX1-related neurodevelopmental disorderLOFAD
DN
0.3793th %ile
GOF
0.3293th %ile
LOF
0.74top 10%

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

LOFprediction above median · 1 literature citation · LOEUF 0.16

Literature Evidence

LOFHaploinsufficiency of CUX1 Causes Nonsyndromic Global Developmental Delay With Possible Catch-up Development.PMID:30014507

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

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CUX1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
HK2-driven histone H3K18 lactylation promotes stromal cell senescence and decidualization deficiency in URSA via CUX1-mediated SASP factor transcription.
Zhao X et al.·Cell Mol Biol Lett
2026Open Access
CUX1::MET fusion defines an indolent subtype of diffuse low-grade glioma, MAPK pathway-altered.
Nagashima H et al.·Acta Neuropathol Commun
2026Open Access
Functional characterization of CASP, a CUX1 isoform, reveals its tumor-promoting role in colorectal cancer via TRIM21-mediated signaling.
Zhou B et al.·iScience
2026Open AccessFunctional
CUX1 restrains latent hematopoietic stem cell plasticity by suppressing stem cell-intrinsic inflammatory pathways.
Martinez TC et al.·Blood
2025
The transcription factor CUX1 exerts opposing roles in human and mouse adipocyte differentiation.
Chen Y et al.·Mol Metab
2026Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients