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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NOTO
notochord homeobox
Chromosome 2 · 2p13.2
NCBI Gene: 344022Ensembl: ENSG00000214513.4HGNC: HGNC:31839UniProt: A8MTQ0
8PubMed Papers
11Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sequence-specific double-stranded DNA bindingprotein bindingRNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription factor activity, RNA polymerase II-specificintelligenceosteomyelitisbreast carcinomarectosigmoid junction neoplasm
✦AI Summary

NOTO (notochord homeobox) is a transcription factor essential for early embryonic development, particularly in notochord and node formation. Acting downstream of FOXA2 and Brachyury, NOTO regulates cell identity through complex gene-regulatory networks during zebrafish embryogenesis 1. A primary function of NOTO involves controlling cilia formation in the posterior notochord and mediating left-right axis patterning by acting upstream of ciliary regulators FOXJ1 and RFX3. NOTO activates transcription of multiple ciliary proteins required for axonemal assembly and function. The gene also plays a critical role in regulating axial versus paraxial mesoderm cell fate specification 1. NOTO mutations have been identified as notochord regulators with documented phenotypic consequences during development, as demonstrated through systematic in silico transcription factor perturbation studies. Loss of noto function produces previously unreported developmental phenotypes, highlighting its importance in coordinating cell identity decisions during embryogenesis 1. These functions establish NOTO as a key developmental transcription factor with implications for understanding left-right asymmetry, ciliogenesis, and mesodermal patterning during vertebrate development.

Sources cited
1
NOTO is an established notochord regulator; loss of noto produces documented phenotypes; NOTO functions in zebrafish embryogenesis and cell identity regulation through transcription factor networks
PMID: 36755098
⚠Limited data available — This gene has 1 indexed publication. Summary and analysis may be incomplete.
Disease Associationsⓘ11
intelligenceOpen Targets
0.29Weak
osteomyelitisOpen Targets
0.24Weak
breast carcinomaOpen Targets
0.04Suggestive
rectosigmoid junction neoplasmOpen Targets
0.02Suggestive
nail-patella syndromeOpen Targets
0.01Suggestive
osteoporosisOpen Targets
0.01Suggestive
agingOpen Targets
0.00Suggestive
gastric carcinomaOpen Targets
0.00Suggestive
atrial fibrillationOpen Targets
0.00Suggestive
lung cancerOpen Targets
0.00Suggestive
ovarian serous cystadenocarcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EMX1Shared pathway100%EMX2Shared pathway100%VAX1Shared pathway100%GSX1Shared pathway100%TBXTProtein interaction82%FOXA1Protein interaction79%
Tissue Expression6 tissues
Ovary
100%
Brain
100%
Lung
80%
Liver
80%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
NOTOEMX1EMX2VAX1GSX1TBXTFOXA1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt A8MTQ0
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.60LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.09 [0.76–1.60]
RankingsWhere NOTO stands among ~20K protein-coding genes
  • #17,662of 20,598
    Most Researched8
  • #15,654of 17,882
    Most Constrained (LOEUF)1.60
Genes detectedNOTO
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
Dissecting cell identity via network inference and in silico gene perturbation.
PMID: 36755098
Nature · 2023
1.00
2
Metabolomics in Newborns.
PMID: 27117660
Adv Clin Chem · 2016
0.90
3
PMID: 30335291
0.80
4
The impact of FMR1 gene mutations on human reproduction and development: a systematic review.
PMID: 27432256
J Assist Reprod Genet · 2016
0.70
5
Gut dysbiosis and multiple sclerosis.
PMID: 32169440
Clin Immunol · 2022
0.60