NISCH nischarin [Homo sapiens (human)] - Gene

Summary

Official Symbol: NISCHprovided by HGNC
Official Full Name: nischarinprovided by HGNC
Primary source: HGNC:HGNC:18006
See related: Ensembl:ENSG00000010322 MIM:615507; AllianceGenome:HGNC:18006
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: I-1; IR1; IRAS; hIRAS
Summary: This gene encodes a nonadrenergic imidazoline-1 receptor protein that localizes to the cytosol and anchors to the inner layer of the plasma membrane. The orthologous mouse protein has been shown to influence cytoskeletal organization and cell migration by binding to alpha-5-beta-1 integrin. In humans, this protein has been shown to bind to the adapter insulin receptor substrate 4 (IRS4) to mediate translocation of alpha-5 integrin from the cell membrane to endosomes. Expression of this protein was reduced in human breast cancers while its overexpression reduced tumor growth and metastasis; possibly by limiting the expression of alpha-5 integrin. In human cardiac tissue, this gene was found to affect cell growth and death while in neural tissue it affected neuronal growth and differentiation. Alternative splicing results in multiple transcript variants encoding differerent isoforms. Some isoforms lack the expected C-terminal domains of a functional imidazoline receptor. [provided by RefSeq, Jan 2013]
Expression: Ubiquitous expression in testis (RPKM 30.5), prostate (RPKM 22.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.1

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (52455604..52493068)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (52488505..52525966)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (52489620..52527084)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Contribution of Nischarin/IRAS in CNS development, injury and diseases.
Title: Contribution of Nischarin/IRAS in CNS development, injury and diseases.
Identification of a psychiatric risk gene NISCH at 3p21.1 GWAS locus mediating dendritic spine morphogenesis and cognitive function.
Title: Identification of a psychiatric risk gene NISCH at 3p21.1 GWAS locus mediating dendritic spine morphogenesis and cognitive function.
Nischarin expression may have differing roles in male and female melanoma patients.
Title: Nischarin expression may have differing roles in male and female melanoma patients.
Transcription factor KLF15 inhibits the proliferation and migration of gastric cancer cells via regulating the TFAP2A-AS1/NISCH axis.
Title: Transcription factor KLF15 inhibits the proliferation and migration of gastric cancer cells via regulating the TFAP2A-AS1/NISCH axis.
These experiments demonstrate an important role of Nischarin in regulating cell attachment, which adds to our understanding of the early events of the metastatic process in breast cancer.
Title: Nischarin regulates focal adhesion and Invadopodia formation in breast cancer cells.
In the prefrontal cortex of long-term opiate/cocaine abusers, IRAS content was increased when compared to matched controls.
Title: Upregulation of IRAS/nischarin (I(1)-imidazoline receptor), a regulatory protein of μ-opioid receptor trafficking, in postmortem prefrontal cortex of long-term opiate and mixed opiate/cocaine abusers.
IRAS is a new mu opioid receptor interacting protein that regulates agonist-induced trafficking of mu opioid receptor.
Title: IRAS Modulates Opioid Tolerance and Dependence by Regulating μ Opioid Receptor Trafficking.
The present data confirmed that Nishcharin might be a novel tumor suppressor and plays an important role in breast cancer cell apoptosis and metastasis, which can be used as a potential therapeutic target for breast cancer treatment.
Title: Expression of Nischarin negatively correlates with estrogen receptor and alters apoptosis, migration and invasion in human breast cancer.
Data found that NISCH was significantly downregulated in ovarian neoplasm through its promotor silencing with hypermethylation and its expression was correlated with poor prognosis.
Title: Frequent Loss of NISCH Promotes Tumor Proliferation and Invasion in Ovarian Cancer via Inhibiting the FAK Signal Pathway.
Nischarin expression may therefore be used as a marker to predict the invasiveness and metastasis of primary breast cancer
Title: Expression of integrin-binding protein Nischarin in metastatic breast cancer.

Submit: New GeneRIF Correction See all GeneRIFs (28)

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
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 13 new risk loci for schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. 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

RH17807 (e-PCR)
- UniSTS:51483

RH91377 (e-PCR)
- UniSTS:91695

MARC_5975-5976:997299498:1 (e-PCR)
- UniSTS:269627

SHGC-32372 (e-PCR)
- UniSTS:21198

WI-18469 (e-PCR)
- UniSTS:55535

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables integrin binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol 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 Rac protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell migration	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in early endosome	IEA Inferred from Electronic Annotation more info
located_in intercellular bridge	IDA Inferred from Direct Assay more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in membrane	HDA more info	PubMed
located_in microtubule cytoskeleton	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in recycling endosome	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: nischarin

Names: I-1 receptor candidate protein; I1R candidate protein; imidazoline receptor 1; imidazoline receptor antisera selected

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_033112.2 RefSeqGene

Range

5002..42466

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001276293.2 → NP_001263222.2 nischarin isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) has its transcription extend past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR, compared to variant 1. It encodes isoform 2 (also known as IRAS-L) which is shorter and has a distinct C-terminus, compared to isoform 1. This isoform lacks multiple domains which are believed to be required by functional imidazoline receptors.

Source sequence(s)

AC006208

Consensus CDS

CCDS63652.1

UniProtKB/TrEMBL

C9J715

Related

ENSP00000417812.1, ENST00000488380.5

Conserved Domains (3) summary

cd06875
Location:14 → 129

PX_IRAS; The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected

COG4886
Location:289 → 418

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:289 → 311

LRR_RI; leucine-rich repeat [structural motif]
NM_001276294.2 → NP_001263223.2 nischarin isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks several exons and includes an alternate 3' terminal exon, resulting in a novel 3' coding region and 3' UTR, compared to variant 1. It encodes isoform 3 (also known as IRAS-S) which is shorter and has a distinct C-terminus, compared to isoform 1. This isoform lacks multiple domains which are believed to be required by functional imidazoline receptors.

Source sequence(s)

AC006208

Consensus CDS

CCDS63651.1

Related

ENSP00000392484.2, ENST00000420808.2

Conserved Domains (3) summary

cd06875
Location:14 → 129

PX_IRAS; The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected

COG4886
Location:289 → 418

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:289 → 311

LRR_RI; leucine-rich repeat [structural motif]
NM_007184.4 → NP_009115.3 nischarin isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1; also known as IRAS-M).

Source sequence(s)

AC006208

Consensus CDS

CCDS33767.1

UniProtKB/Swiss-Prot

C9J245, Q6PGP3, Q6PIB4, Q7L8M3, Q7Z2X6, Q9UES6, Q9UEU4, Q9UFW3, Q9Y2I1

UniProtKB/TrEMBL

B3KNF9

Related

ENSP00000339958.4, ENST00000345716.9

Conserved Domains (3) summary

cd06875
Location:14 → 129

PX_IRAS; The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected

COG4886
Location:289 → 418

LRR; Leucine-rich repeat (LRR) protein [Transcription]

sd00033
Location:289 → 311

LRR_RI; leucine-rich repeat [structural motif]