NTN1

netrin 1, the group of Netrins

Basic information

Region (hg38): 17:9021509-9244000

Links

ENSG00000065320 ∙ NCBI:9423 ∙ OMIM:601614 ∙ HGNC:8029 ∙ Uniprot:O95631 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial congenital mirror movements (Supportive), mode of inheritance: AD
• mirror movements 4 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mirror movements 4	AD	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	Neurologic	28945198

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NTN1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NTN1 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				13	5	18
missense			37	3		40
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding					1	1
Total	0	0	40	16	6

Variants in NTN1

This is a list of pathogenic ClinVar variants found in the NTN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-9022381-G-T		not specified	Uncertain significance (May 28, 2024)
17-9022419-G-T		not specified	Likely benign (Apr 07, 2023)
17-9022489-A-G		not specified	Uncertain significance (Jan 09, 2024)
17-9022490-T-C		NTN1-related disorder	Likely benign (Apr 17, 2023)
17-9022493-C-T		NTN1-related disorder	Likely benign (Jul 01, 2024)
17-9022592-C-T		NTN1-related disorder	Likely benign (Jun 21, 2023)
17-9022593-C-T		not specified	Uncertain significance (Mar 08, 2024)
17-9022647-C-A		not specified	Uncertain significance (Jan 29, 2024)
17-9022715-G-T		NTN1-related disorder	Benign (Jun 05, 2019)
17-9022734-C-A		not specified	Uncertain significance (Feb 27, 2023)
17-9022744-A-C		not specified	Uncertain significance (Dec 01, 2022)
17-9022757-C-G		not specified	Uncertain significance (Aug 04, 2023)
17-9022859-C-G		not specified	Uncertain significance (May 04, 2022)
17-9022892-C-T			Likely benign (Jul 01, 2023)
17-9022893-T-C		not specified	Uncertain significance (Jun 29, 2023)
17-9022909-C-T		not specified	Uncertain significance (May 18, 2023)
17-9022930-A-G		not specified	Uncertain significance (Jul 05, 2023)
17-9022933-G-A		not specified	Uncertain significance (Mar 30, 2024)
17-9022984-C-G		not specified	Uncertain significance (Oct 18, 2021)
17-9023001-A-G		NTN1-related disorder	Likely benign (Apr 20, 2020)
17-9023004-C-A		NTN1-related disorder	Likely benign (Jul 28, 2020)
17-9023008-C-T		not specified	Uncertain significance (Sep 06, 2022)
17-9023098-T-C		Orofacial cleft 1	Uncertain significance (Nov 22, 2022)
17-9023103-G-A		NTN1-related disorder	Uncertain significance (Apr 02, 2023)
17-9023105-C-G		NTN1-related disorder	Likely benign (Aug 15, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NTN1	protein_coding	protein_coding	ENST00000173229	6	222459

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00313	125698	0	13	125711	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.27	248	371	0.668	0.0000204	3935
Missense in Polyphen		107	184.79	0.57905		1857
Synonymous	0.821	147	160	0.917	0.00000906	1160
Loss of Function	4.08	1	21.4	0.0468	9.14e-7	249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000756	0.0000756
Ashkenazi Jewish	0.000128	0.0000993
East Asian	0.00	0.00
Finnish	0.0000985	0.0000924
European (Non-Finnish)	0.0000357	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000542	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. It also serve as a survival factor via its association with its receptors which prevent the initiation of apoptosis. Involved in tumorigenesis by regulating apoptosis. {ECO:0000269|PubMed:15343335}.
• Pathway: Axon guidance - Homo sapiens (human);Spinal Cord Injury;Chromosomal and microsatellite instability in colorectal cancer;Developmental Biology;DSCAM interactions;Alpha6Beta4Integrin;Regulation of commissural axon pathfinding by SLIT and ROBO;DCC mediated attractive signaling;Netrin mediated repulsion signals;Role of second messengers in netrin-1 signaling;Netrin-1 signaling;Signaling by ROBO receptors;Axon guidance;Netrin-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.255

Intolerance Scores

• loftool: 0.164
• rvis_EVS: -0.63
• rvis_percentile_EVS: 17.03

Haploinsufficiency Scores

• pHI: 0.951
• ghis: 0.642

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.859

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ntn1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; cellular phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hearing/vestibular/ear phenotype

Zebrafish Information Network

• Gene name: ntn1a
• Affected structure: VaP motor neuron
• Phenotype tag: abnormal
• Phenotype quality: increased branchiness

Gene ontology

• Biological process: neuron migration;apoptotic process;substrate-dependent cell migration, cell extension;nuclear migration;Ras protein signal transduction;positive regulation of cell population proliferation;regulation of cell migration;negative regulation of axon extension;Cdc42 protein signal transduction;anterior/posterior axon guidance;inner ear morphogenesis;positive regulation of axon extension;regulation of synapse assembly;mammary gland duct morphogenesis;cell-cell adhesion;negative regulation of netrin-activated signaling pathway;positive regulation of cell motility
• Cellular component: extracellular region;basement membrane;cytoplasm
• Molecular function: protein binding