NTN4

protein-coding

netrin 4, the group of Netrins

Gene summary

This gene encodes a member of the netrin family of proteins, which function in various biological processes including axon guidance, tumorogenesis, and angiogenesis. Netrins are laminin-related proteins that have an N-terminal laminin-type domain, epidermal growth factor-like repeat domain, and a positively charged heparin-binding domain at the C-terminus. The protein encoded by this gene is involved in processes including neurite growth and migration, angiogenesis and mural cell adhesion to endothelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

MANE transcript

NM_021229.4

Inheritance

—

ClinVar variants

U:71B:12

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr12:95,657,807-95,791,189

External References & Databases

Ensembl (ENSG00000074527)

Transcript & Mutation Effects

hg38 • Region Span ~133.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NTN4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 10

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021229.4. 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				1 clinvar	2 clinvar	3
missense			69 clinvar	9 clinvar		78
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	71	10	2	83

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021229.4	RefSeq	NP_067052.2	10	MANE Select
ENST00000343702.9	Ensembl	ENSP00000340998.4	10	MANE Select
NM_001329700.2	RefSeq	NP_001316629.1	9	Standard
NM_001329701.2	RefSeq	NP_001316630.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Developmental Biology
Extracellular matrix organization
Netrin-1 signaling
Non-integrin membrane-ECM interactions

Biological Process

axon guidance
neuron remodeling
regulation of branching involved in salivary gland morphogenesis by extracellular matrix-epithelial cell signaling

Molecular Function

protein binding
laminin-1 binding

Cellular Component

basement membrane
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343702
Coding exons: 10
Length: 133348
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125748
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.74	273	367	0.744	0.0000206	4120
Missense (PolyPhen)		81	143.33	0.56512		1618
Synonymous	0.779	125	137	0.915	0.00000792	1172
Loss of Function	4.49	6	34.4	0.174	0.00000205	379

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00012	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play an important role in neural, kidney and vascular development. Promotes neurite elongation from olfactory bulb explants. {ECO:0000269|PubMed:11038171}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.390
RVIS EVS: -0.26
RVIS percentile EVS: 34.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.455

Gene Damage Prediction

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