CUX1

Chr 7AD

cut like homeobox 1

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

NCBI Gene: 1523ENSG00000257923UniProt: P39880

The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It may regulate gene expression, morphogenesis, and differentiation and it may also play a role in the cell cycle progession. Several alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Feb 2011]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with developmental delay and with or without motor or speech delayMIM #618330
AD
580
ClinVar variants
78
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
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.
📋
ClinVar Variants
78 Pathogenic / Likely Pathogenic· 359 VUS of 580 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.04–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.59–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 6 / 72.7Missense obs/exp: 543 / 850.7Syn Z: -0.54

ClinVar Variant Classifications

580 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic36
VUS359
Likely Benign109
Benign24
Conflicting10
42
Pathogenic
36
Likely Pathogenic
359
VUS
109
Likely Benign
24
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
36
0
42
Likely Pathogenic
19
1
16
0
36
VUS
15
303
40
1
359
Likely Benign
1
42
9
57
109
Benign
0
3
12
9
24
Conflicting
—10
Total4134911367580

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

View in 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.

Gene2Phenotype Curations

CUX1-related neurodevelopmental disorder

moderate
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
splice region variantframeshift variantstop gainedmissense variantwhole partial gene deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with developmental delay and with or without motor or speech delay

MIM #618330

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CUX1-related neurodevelopmental disorder: deep insights into phenotype-genotype spectrum and underlying pathology.
Oppermann H et al.·Eur J Hum Genet
2023
The significance of CUX1 and chromosome 7 in myeloid malignancies.
Jotte MRM et al.·Curr Opin Hematol
2022Review
Distinct clinical and biological implications of CUX1 in myeloid neoplasms.
Aly M et al.·Blood Adv
2019
Designing Myeloid Gene Panels.
Zhao F et al.·Arch Pathol Lab Med
2022
Genomic studies controvert the existence of the CUX1 p75 isoform.
Krishnan M et al.·Sci Rep
2022
Abnormal expression of CUX1 influences autophagy activation in paroxysmal nocturnal hemoglobinuria.
Wu J et al.·J Leukoc Biol
2024
Patient-specific mutation of Dync1h1 in mice causes brain and behavioral deficits.
Ramos RL et al.·Neurobiol Dis
2024
Inactivating CUX1 mutations promote tumorigenesis.
Wong CC et al.·Nat Genet
2014
The molecular pathogenesis of the myelodysplastic syndromes.
Pellagatti A et al.·Eur J Haematol
2015Review
Real world predictors of response and 24-month survival in high-grade TP53-mutated myeloid neoplasms.
Kaur A et al.·Blood Cancer J
2024
Top 10 resultsSearch 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
2026
CUX1::MET fusion defines an indolent subtype of diffuse low-grade glioma, MAPK pathway-altered.
Nagashima H et al.·Acta Neuropathol Commun
2026
Functional characterization of CASP, a CUX1 isoform, reveals its tumor-promoting role in colorectal cancer via TRIM21-mediated signaling.
Zhou B et al.·iScience
2026🔓 Open 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
2026🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools