NTN4 netrin 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NTN4provided by HGNC
Official Full Name: netrin 4provided by HGNC
Primary source: HGNC:HGNC:13658
See related: Ensembl:ENSG00000074527 MIM:610401; AllianceGenome:HGNC:13658
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PRO3091
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]
Expression: Broad expression in spleen (RPKM 88.7), kidney (RPKM 62.7) and 20 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q22

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (95657807..95791155, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (95636970..95770314, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (96051583..96184933, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Hepatic Expression of NTN4 and Its Receptors in Patients with Hepatocellular Carcinoma.
Title: Hepatic Expression of NTN4 and Its Receptors in Patients with Hepatocellular Carcinoma.
RNA-binding protein quaking 5 inhibits the progression of non-small cell lung cancer by upregulating netrin-4 expression.
Title: RNA‑binding protein quaking 5 inhibits the progression of non‑small cell lung cancer by upregulating netrin‑4 expression.
Netrin-4: Focus on Its Role in Axon Guidance, Tissue Stability, Angiogenesis and Tumors.
Title: Netrin-4: Focus on Its Role in Axon Guidance, Tissue Stability, Angiogenesis and Tumors.
NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer.
Title: NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer.
The Interaction of NTN4 and miR-17-92 Polymorphisms on Breast Cancer Susceptibility in a Chinese Population.
Title: The Interaction of NTN4 and miR-17-92 Polymorphisms on Breast Cancer Susceptibility in a Chinese Population.
Netrin-4 expression by human endothelial cells inhibits endothelial inflammation and senescence.
Title: Netrin-4 expression by human endothelial cells inhibits endothelial inflammation and senescence.
Anti-Inflammatory Role of Netrin-4 in Diabetic Retinopathy.
Title: Anti-Inflammatory Role of Netrin-4 in Diabetic Retinopathy.
Enrichment of damaging missense variants in genes related with axonal guidance signalling in sporadic Meniere's disease.
Title: Enrichment of damaging missense variants in genes related with axonal guidance signalling in sporadic Meniere's disease.
eQTL Colocalization Analyses Identify NTN4 as a Candidate Breast Cancer Risk Gene.
Title: eQTL Colocalization Analyses Identify NTN4 as a Candidate Breast Cancer Risk Gene.
Findings indicate that activation of notch receptor 1 (Notch1) signalling significantly up-regulated Netrin4 (NTN4) mRNA and protein expressions.
Title: Notch1 activates angiogenic regulator Netrin4 in endothelial cells.

Submit: New GeneRIF Correction See all GeneRIFs (35)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study in Koreans identifies susceptibility loci for allergic nickel dermatitis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association studies identify four ER negative-specific breast cancer risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genotyping identifies 41 new loci associated with breast cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH103736 (e-PCR)
- UniSTS:98061

RH77787 (e-PCR)
- UniSTS:21642

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables laminin-1 binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in animal organ morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in basement membrane assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuron remodeling	IEA Inferred from Electronic Annotation more info
involved_in regulation of branching involved in salivary gland morphogenesis by extracellular matrix-epithelial cell signaling	IEA Inferred from Electronic Annotation more info
involved_in substrate adhesion-dependent cell spreading	IBA Inferred from Biological aspect of Ancestor more info
involved_in tissue development	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in extracellular region	IEA Inferred from Electronic Annotation more info
part_of laminin complex	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: netrin-4

Names: beta-netrin; hepar-derived netrin-like protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_051252.1 RefSeqGene

Range

5443..138400

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001329700.2 → NP_001316629.1 netrin-4 isoform 2 precursor

Status: REVIEWED

Source sequence(s)

AK290591, AK315796, AL137540, AY330211, BI549738, DB473670

Consensus CDS

CCDS86325.1

UniProtKB/TrEMBL

B2RE43

Related

ENSP00000447292.1, ENST00000553059.1

Conserved Domains (5) summary

smart00180
Location:395 → 446

EGF_Lam; Laminin-type epidermal growth factor-like domai

cd00055
Location:261 → 320

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

pfam00053
Location:332 → 392

Laminin_EGF; Laminin EGF domain

pfam00055
Location:43 → 260

Laminin_N; Laminin N-terminal (Domain VI)

cl02512
Location:504 → 603

NTR_like; NTR_like domain; a beta barrel with an oligosaccharide/oligonucleotide-binding fold found in netrins, complement proteins, tissue inhibitors of metalloproteases (TIMP), and procollagen C-proteinase enhancers (PCOLCE), amongst others. In netrins, the ...
NM_001329701.2 → NP_001316630.1 netrin-4 isoform 3

Status: REVIEWED

Source sequence(s)

AF297711, AK290591, AL137540, BP232567

Consensus CDS

CCDS86324.1

UniProtKB/TrEMBL

A8K3H6

Related

ENSP00000444432.1, ENST00000538383.5
NM_001329702.2 → NP_001316631.1 netrin-4 isoform 3

Status: REVIEWED

Source sequence(s)

AC008128, AC090001, AL137540

Consensus CDS

CCDS86324.1

UniProtKB/TrEMBL

A8K3H6
NM_021229.4 → NP_067052.2 netrin-4 isoform 1 precursor

See identical proteins and their annotated locations for NP_067052.2

Status: REVIEWED

Source sequence(s)

AC090001, AF297711, AL833767, BC013591, BI549738

Consensus CDS

CCDS9054.1

UniProtKB/Swiss-Prot

B2RNC2, Q658K9, Q7L3F1, Q7L9D6, Q7Z5B6, Q9BZP1, Q9HB63, Q9NT44, Q9P133

UniProtKB/TrEMBL

B2RE43

Related

ENSP00000340998.4, ENST00000343702.9

Conserved Domains (5) summary

smart00180
Location:395 → 446

EGF_Lam; Laminin-type epidermal growth factor-like domai

cd00055
Location:261 → 320

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd03578
Location:516 → 626

NTR_netrin-4_like; NTR domain, Netrin-4-like subfamily; composed of the C-terminal NTR domains of netrin-4 (beta netrin) and similar proteins. Netrins are secreted proteins that function as tropic cues in the direction of axon growth and cell migration during neural ...

pfam00053
Location:332 → 392

Laminin_EGF; Laminin EGF domain

pfam00055
Location:43 → 260

Laminin_N; Laminin N-terminal (Domain VI)