NHS Gene

Name	Nance-Horan syndrome (congenital cataracts and dental anomalies)
Description	This gene encodes a protein containing four conserved nuclear localization signals. The encoded protein functions in eye, tooth, craniofacial and brain development, and it can regulate actin remodeling and cell morphology. Mutations in this gene have been shown to cause Nance-Horan syndrome, and also X-linked cataract-40. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe NHS gene plays a pivotal role during early development by orchestrating the formation and differentiation of multiple organ systems including the eye, tooth, brain, and craniofacial structures. Expression studies in humans and animal models demonstrate that NHS is temporally and spatially regulated during embryogenesis, and its localization on Xp22.13 has allowed the identification of many mutations that disrupt these developmental processes and lead to congenital cataracts and associated malformations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the cellular level the NHS protein exists as multiple isoforms—most notably NHS-A and NHS-1A—that display distinct subcellular localizations and functions. The NHS-A isoform has been shown to concentrate at the cell membrane and particularly at cell–cell contacts, where it co-localizes with tight junction proteins (for example, ZO-1) and localizes to regions associated with lamellipodia and focal adhesions. These studies also reveal a role for NHS in regulating actin cytoskeletal remodeling and maintaining proper cell morphology, with its N-terminal WAVE homology domain mediating interactions with actin regulatory proteins."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComprehensive mutational analyses have identified that various disruptive alterations—including protein-truncating mutations, copy number variations, and even missense changes—lead to loss or misregulation of NHS function. Such molecular defects interfere with NHS’s role in coordinating cytoskeletal dynamics, regulating intercellular adhesion, and facilitating proper signal transduction during development. The resulting cascade of pathophysiological effects manifests as a spectrum of clinical features, from severe bilateral congenital cataracts and dental anomalies to craniofacial dysmorphism and intellectual disability. These findings underscore the multifaceted regulatory functions of NHS in development and cellular architecture, and highlight how different mutational mechanisms—from aberrant transcriptional control to complete loss-of-function—contribute to phenotypic heterogeneity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kathryn P Burdon, James D McKay, Michèle M Sale, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/379381"}], "href": "https://doi.org/10.1086/379381"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14564667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14564667"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S P Brooks, N D Ebenezer, S Poopalasundaram, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the gene for Nance-Horan syndrome (NHS)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2004.022517"}], "href": "https://doi.org/10.1136/jmg.2004.022517"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15466011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15466011"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Vedam Lakshmi Ramprasad, Alka Thool, Sakthivel Murugan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Truncating mutation in the NHS gene: phenotypic heterogeneity of Nance-Horan syndrome in an asian Indian family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.04-0477"}], "href": "https://doi.org/10.1167/iovs.04-0477"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15623749"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15623749"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kristen M Huang, Junhua Wu, Simon P Brooks, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A novel Xp22.13 microdeletion in Nance-Horan syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Birth Defects Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/bdr2.1032"}], "href": "https://doi.org/10.1002/bdr2.1032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28464487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28464487"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Nadav Shoshany, Isaac Avni, Yair Morad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NHS Gene Mutations in Ashkenazi Jewish Families with Nance-Horan Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Eye Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/02713683.2017.1304560"}], "href": "https://doi.org/10.1080/02713683.2017.1304560"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28557584"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28557584"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Laura Gómez-Laguna, Alejandro Martínez-Herrera, Alejandra Del Pilar Reyes-de la Rosa, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Nance-Horan syndrome protein, NHS, associates with epithelial cell junctions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddl120"}], "href": "https://doi.org/10.1093/hmg/ddl120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16675532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16675532"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shiwani Sharma, Kathryn P Burdon, Alpana Dave, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The Nance-Horan syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddq125"}], "href": "https://doi.org/10.1093/hmg/ddq125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20332100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20332100"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Margherita Coccia, Simon P Brooks, Tom R Webb, et al. "}, {"type": "b", "children": [{"type": "t", "text": "X-linked cataract and Nance-Horan syndrome are allelic disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp206"}], "href": "https://doi.org/10.1093/hmg/ddp206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19414485"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19414485"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Manèl Chograni, Imen Rejeb, Lamia Ben Jemaa, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A Turkish family with Nance-Horan Syndrome due to a novel mutation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2013.03.094"}], "href": "https://doi.org/10.1016/j.gene.2013.03.094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23566852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23566852"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Wenmin Sun, Xueshan Xiao, Shiqiang Li, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Zhejiang Univ Sci B (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1631/jzus.B1300321"}], "href": "https://doi.org/10.1631/jzus.B1300321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25091991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25091991"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Aijun Li, Bingzhen Li, Lemeng Wu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Whole exome sequencing identified a novel truncation mutation in the NHS gene associated with Nance-Horan syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12881-018-0725-3"}], "href": "https://doi.org/10.1186/s12881-018-0725-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30642278"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30642278"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "V Hernández, I Pascual-Camps, M J Aparisi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Great clinical variability of Nance Horan syndrome due to deleterious "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "NHS"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " mutations in two unrelated Spanish families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ophthalmic Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/13816810.2019.1692362"}], "href": "https://doi.org/10.1080/13816810.2019.1692362"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31755796"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31755796"}]}]}]}
Synonyms	CTRCT40, SCML1, CXN
Proteins	NHS_HUMAN
NCBI Gene ID	4810
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NHS has 7,669 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 113 datasets.

Click the + buttons to view associations for NHS from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NHS Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NHS gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of NHS gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of NHS gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NHS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of NHS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NHS gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NHS gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NHS gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of NHS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NHS protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NHS gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NHS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NHS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of NHS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with NHS gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with NHS gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing NHS protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NHS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NHS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NHS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with NHS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of NHS gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NHS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NHS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NHS gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with NHS gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NHS protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by NHS gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving NHS gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving NHS gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with NHS gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NHS gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with NHS gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with NHS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NHS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NHS gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NHS gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NHS gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing NHS from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with NHS gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.