NRG2

neuregulin 2, the group of I-set domain containing|Neuregulins

Basic information

Region (hg38): 5:139846778-140043299

Links

ENSG00000158458 ∙ NCBI:9542 ∙ OMIM:603818 ∙ HGNC:7998 ∙ Uniprot:O14511 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NRG2 gene.

• Inborn genetic diseases (60 variants)
• not provided (3 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NRG2 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						0
missense			52	8		60
nonsense						0
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding						0
Total	0	0	53	8	1

Variants in NRG2

This is a list of pathogenic ClinVar variants found in the NRG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-139848050-G-A		not specified	Uncertain significance (Dec 01, 2023)
5-139848069-C-A		not specified	Uncertain significance (Jul 13, 2021)
5-139848071-C-G		not specified	Likely benign (Apr 07, 2023)
5-139848096-T-G		not specified	Uncertain significance (Feb 21, 2024)
5-139848102-C-T		not specified	Uncertain significance (Aug 19, 2023)
5-139848194-G-A		not specified	Uncertain significance (Nov 18, 2022)
5-139848200-C-G		not specified	Uncertain significance (Jun 22, 2023)
5-139848201-G-A		not specified	Uncertain significance (Oct 26, 2022)
5-139848207-G-C		not specified	Uncertain significance (Aug 15, 2023)
5-139848215-G-T		not specified	Uncertain significance (Jan 04, 2022)
5-139848221-C-A		not specified	Uncertain significance (Apr 25, 2022)
5-139848246-G-C		not specified	Uncertain significance (Apr 12, 2023)
5-139848261-A-G		not specified	Uncertain significance (Jun 30, 2022)
5-139848264-T-C		not specified	Uncertain significance (Mar 27, 2023)
5-139848273-A-G		not specified	Uncertain significance (Jul 20, 2021)
5-139848284-G-T		not specified	Uncertain significance (Sep 23, 2023)
5-139848291-G-A		not specified	Uncertain significance (May 31, 2022)
5-139848293-C-G		not specified	Uncertain significance (Apr 07, 2023)
5-139848348-G-C		not specified	Uncertain significance (Jan 08, 2024)
5-139848375-T-C		not specified	Uncertain significance (Nov 07, 2022)
5-139848380-A-G		not specified	Uncertain significance (Aug 30, 2021)
5-139848399-A-C		not specified	Uncertain significance (Jan 18, 2023)
5-139848420-G-A		not specified	Uncertain significance (Dec 16, 2023)
5-139848467-G-A		not specified	Uncertain significance (Oct 12, 2021)
5-139848479-G-C		not specified	Uncertain significance (Feb 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NRG2	protein_coding	protein_coding	ENST00000361474	10	196521

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000746	125724	0	2	125726	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.27	281	411	0.684	0.0000238	5373
Missense in Polyphen		110	175.49	0.62683		2177
Synonymous	1.06	161	179	0.899	0.0000110	1786
Loss of Function	4.70	2	29.6	0.0675	0.00000151	366

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000886	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. May also promote the heterodimerization with the EGF receptor.
• Pathway: ErbB signaling pathway - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;EGF-Core;ErbB Signaling Pathway;SHC1 events in ERBB2 signaling;Signaling by PTK6;Disease;Signal Transduction;neuroregulin receptor degredation protein-1 controls erbb3 receptor recycling;g-secretase mediated erbb4 signaling pathway;ERBB2 Activates PTK6 Signaling;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;ErbB4 signaling events;GPCR signaling-G alpha s Epac and ERK;Downregulation of ERBB2:ERBB3 signaling;Downregulation of ERBB2 signaling;GPCR signaling-G alpha s PKA and ERK;agrin in postsynaptic differentiation;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;GRB2 events in ERBB2 signaling;Signaling by Non-Receptor Tyrosine Kinases;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K events in ERBB2 signaling;GRB7 events in ERBB2 signaling;Signaling by ERBB2;ERBB2 Regulates Cell Motility;SHC1 events in ERBB4 signaling;PI3K/AKT Signaling in Cancer;PI3K events in ERBB4 signaling;GPCR signaling-G alpha i;Nuclear signaling by ERBB4;Signaling by ERBB4;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Diseases of signal transduction;ErbB receptor signaling network (Consensus)

Recessive Scores

• pRec: 0.148

Haploinsufficiency Scores

• pHI: 0.871
• hipred: Y
• hipred_score: 0.647
• ghis: 0.513

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.898

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nrg2
• Phenotype: reproductive system 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); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: nrg2a
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: MAPK cascade;signal transduction;nervous system development;regulation of signaling receptor activity;peptidyl-tyrosine phosphorylation;intracellular signal transduction;ERBB2 signaling pathway;phosphatidylinositol phosphorylation;positive regulation of protein kinase B signaling;regulation of cell motility
• Cellular component: extracellular region;extracellular space;plasma membrane;integral component of membrane
• Molecular function: protein tyrosine kinase activity;Ras guanyl-nucleotide exchange factor activity;signaling receptor binding;growth factor activity;phosphatidylinositol-4,5-bisphosphate 3-kinase activity