NTN1

protein-coding

netrin 1, the group of Netrins

Gene summary

Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon guidance and cell migration during development. Mutations and loss of expression of netrin suggest that variation in netrin may be involved in cancer development. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004822.3

Inheritance

ClinVar variants

P:2U:87B:24

Top phenotype

Mirror movements 4

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr17:9,021,510-9,244,000

External References & Databases

Ensembl (ENSG00000065320)

Transcript & Mutation Effects

hg38 • Region Span ~222.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial congenital mirror movementsSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016558

Submitter: Orphanet

mirror movements 4STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032641

Submitter: Labcorp Genetics (formerly Invitae)

multiple congenital anomalies/dysmorphic syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019042

Submitter: Ambry Genetics

mirror movements 4STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032641

Submitter: PanelApp Australia

mirror movements 4LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032641

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Mirror movements 4AD

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 28945198

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NTN1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 92

NTN1-related disorderTotal: 28

Mirror movements 4Total: 6

not providedTotal: 5

Mirror movements 1Total: 2

Orofacial cleft 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004822.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				16 clinvar	3 clinvar	19
missense	2 clinvar		85 clinvar	5 clinvar		92
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	2	0	87	21	3	113

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004822.3	RefSeq	NP_004813.2	6	MANE Select
ENST00000173229.7	Ensembl	ENSP00000173229.2	6	MANE Select
ENST00000436734.1	Ensembl	ENSP00000389375.2	4	Standard
ENST00000962853.1	Ensembl	ENSP00000632912.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ntn1a	Danio rerio	Structure: VaP motor neuron Quality: increased branchiness abnormal

Gene / Model

Organism

Observed Phenotype

ntn1a

Danio rerio

Structure: VaP motor neuron

Quality: increased branchiness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Spinal Cord Injury
Chromosomal and microsatellite instability in colorectal cancer
Developmental Biology
DSCAM interactions

Biological Process

neuron migration
apoptotic process
substrate-dependent cell migration, cell extension
nuclear migration
Ras protein signal transduction

Molecular Function

protein binding

Cellular Component

extracellular region
basement membrane
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000173229
Coding exons: 6
Length: 222459
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125711
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.27	248	371	0.668	0.0000204	3935
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000076	0.000058	rare
Ashkenazi Jewish	0.00013	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000099	0.000092	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00054	0.00049	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.255

Intolerance Scores

LoFtool: 0.164
RVIS EVS: -0.63
RVIS percentile EVS: 17.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.859

Gene Damage Prediction

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