NOTO

notochord homeobox, the group of NKL subclass homeoboxes and pseudogenes

Basic information

Region (hg38): 2:73202574-73212513

Links

ENSG00000214513 ∙ NCBI:344022 ∙ ∙ HGNC:31839 ∙ Uniprot:A8MTQ0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NOTO gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			22	3		25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	22	3	0

Variants in NOTO

This is a list of pathogenic ClinVar variants found in the NOTO region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-73202739-G-A		not specified	Uncertain significance (Dec 07, 2021)
2-73202752-C-T		not specified	Uncertain significance (Jan 01, 2025)
2-73202820-G-A		not specified	Uncertain significance (Jul 09, 2024)
2-73202833-C-G		not specified	Uncertain significance (Feb 04, 2025)
2-73202900-C-G		not specified	Likely benign (Mar 13, 2023)
2-73202922-G-T		not specified	Uncertain significance (Sep 26, 2023)
2-73202988-T-C		not specified	Uncertain significance (Jan 08, 2025)
2-73203021-T-C		not specified	Uncertain significance (Aug 15, 2023)
2-73208454-C-T		not specified	Uncertain significance (Nov 13, 2023)
2-73208474-G-A		not specified	Uncertain significance (Jan 08, 2024)
2-73208496-G-A		not specified	Uncertain significance (Nov 09, 2024)
2-73208527-G-C		not specified	Uncertain significance (Feb 02, 2022)
2-73208531-G-A		not specified	Uncertain significance (Dec 07, 2024)
2-73208568-A-C		not specified	Uncertain significance (May 23, 2023)
2-73208591-C-T		not specified	Uncertain significance (Jun 05, 2023)
2-73208600-C-G		not specified	Uncertain significance (May 21, 2024)
2-73208610-A-G		not specified	Uncertain significance (Jul 03, 2024)
2-73210774-A-G		not specified	Uncertain significance (Oct 06, 2021)
2-73210811-A-G		not specified	Uncertain significance (Apr 07, 2023)
2-73210846-G-A		not specified	Uncertain significance (Sep 30, 2021)
2-73210846-G-C		not specified	Uncertain significance (Dec 06, 2023)
2-73210864-G-A		not specified	Uncertain significance (Aug 30, 2021)
2-73210880-C-T		not specified	Uncertain significance (Apr 12, 2022)
2-73210882-A-G		not specified	Uncertain significance (Oct 09, 2024)
2-73210883-T-A		not specified	Likely benign (Jun 23, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NOTO	protein_coding	protein_coding	ENST00000398468	3	10256

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00211	0.764	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.236	106	113	0.937	0.00000563	1559
Missense in Polyphen		29	30.258	0.95841		428
Synonymous	1.56	36	50.0	0.720	0.00000275	557
Loss of Function	0.941	5	7.84	0.637	4.26e-7	84

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)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription regulator acting downstream of both FOXA2 and Brachyury (T) during notochord development. Required for node morphogenesis. Is essential for cilia formation in the posterior notochord (PNC) and for left-right patterning; acts upstream of FOXJ1 and RFX3 in this process and is required for the expression of various components important for axonemal assembly and function. Plays a role in regulating axial versus paraxial cell fate. Activates the transcription of ciliary proteins C11orf97 homolog, FAM183B and SPACA9 in the embryonic ventral node (By similarity). {ECO:0000250|UniProtKB:Q5TIS6}.

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.191

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Noto
• Phenotype: limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype

Zebrafish Information Network

• Gene name: noto
• Affected structure: podocyte
• Phenotype tag: abnormal
• Phenotype quality: mislocalised laterally

Gene ontology

• Biological process: heart looping;regulation of transcription by RNA polymerase II;embryonic pattern specification;dorsal/ventral pattern formation;notochord development;motile cilium assembly;regulation of cilium assembly
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding