NHS

NHS actin remodeling regulator, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): X:17375200-17735994

Links

ENSG00000188158 ∙ NCBI:4810 ∙ OMIM:300457 ∙ HGNC:7820 ∙ Uniprot:Q6T4R5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Nance-Horan syndrome (Moderate), mode of inheritance: XL
• Nance-Horan syndrome (Supportive), mode of inheritance: XL
• early-onset nuclear cataract (Supportive), mode of inheritance: AD
• Nance-Horan syndrome (Definitive), mode of inheritance: XL
• Nance-Horan syndrome (Strong), mode of inheritance: XL
• Nance-Horan syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nance-Horan syndrome; Cataract 40	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	4470901; 458526; 11836358; 14564667; 15623749; 16736028; 17256798; 19414485; 20882036; 25266737

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NHS gene.

• Nance-Horan_syndrome (402 variants)
• Inborn_genetic_diseases (192 variants)
• not_provided (180 variants)
• not_specified (40 variants)
• NHS-related_disorder (35 variants)
• Cataract_40 (17 variants)
• Intellectual_disability (11 variants)
• Developmental_cataract (2 variants)
• See_cases (2 variants)
• History_of_neurodevelopmental_disorder (1 variants)
• X-linked_syndromic_intellectual_disability (1 variants)
• Congenital_ocular_coloboma (1 variants)
• Prostate_cancer (1 variants)
• Lymphedema (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NHS gene is commonly pathogenic or not. These statistics are base on transcript: NM_001291867.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	108	27	142
missense	1		244	88	28	361
nonsense	17	3	1			21
start loss						0
frameshift	27	8	1			36
splice donor/acceptor (+/-2bp)	7	2				9
Total	52	13	253	196	55

Highest pathogenic variant AF is 9.10615e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NHS	protein_coding	protein_coding	ENST00000380060	8	360572

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000507	120940	1	1	120942	0.00000827

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.82	495	623	0.795	0.0000505	10612
Missense in Polyphen		196	297.75	0.65828		4898
Synonymous	1.30	221	247	0.895	0.0000203	3406
Loss of Function	5.42	0	34.1	0.00	0.00000278	600

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000253	0.0000185
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function in cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. Involved in the regulation eye, tooth, brain and craniofacial development. {ECO:0000269|PubMed:20332100}.
• Disease: DISEASE: Cataract 40 (CTRCT40) [MIM:302200]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT40 manifests as a congenital nuclear opacity with severe visual impairment in affected males. Heterozygous females have suture cataracts and only slight reduction in vision. In some cases, cataract is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye. {ECO:0000269|PubMed:19414485}. Note=The disease is caused by mutations affecting the gene represented in this entry. Caused by copy number variations predicted to result in altered transcriptional regulation of the NHS gene: a 0.8 Mb segmental duplication-triplication encompassing the NHS, SCML1 and RAI2 genes, and an 4.8 kb intragenic deletion in NHS intron 1.

Recessive Scores

• pRec: 0.148

Intolerance Scores

• rvis_EVS: -0.73
• rvis_percentile_EVS: 14.24

Haploinsufficiency Scores

• pHI: 0.177
• hipred: Y
• hipred_score: 0.715
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0565

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nhs
• Phenotype: vision/eye phenotype

Gene ontology

• Biological process: lens development in camera-type eye;cell differentiation
• Cellular component: Golgi apparatus;bicellular tight junction;focal adhesion;apical plasma membrane;nuclear body;lamellipodium;cell junction