NRG4

neuregulin 4, the group of Neuregulins

Basic information

Region (hg38): 15:75935968-76059795

Links

ENSG00000169752 ∙ NCBI:145957 ∙ OMIM:610894 ∙ HGNC:29862 ∙ Uniprot:Q8WWG1 ∙ 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 NRG4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NRG4 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			8		1	9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	0	1

Variants in NRG4

This is a list of pathogenic ClinVar variants found in the NRG4 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-75955953-T-C		not specified	Uncertain significance (Aug 15, 2023)
15-75955955-G-A		not specified	Uncertain significance (Dec 27, 2023)
15-75955974-C-T		not specified	Uncertain significance (Apr 23, 2024)
15-75955994-C-G		not specified	Uncertain significance (Nov 21, 2023)
15-75961846-G-T		not specified	Uncertain significance (Oct 13, 2023)
15-75961912-T-G		not specified	Uncertain significance (Aug 09, 2021)
15-75961945-C-A		not specified	Uncertain significance (Jul 20, 2021)
15-75961957-G-A		not specified	Uncertain significance (May 30, 2024)
15-75961970-C-T			Benign (Jun 14, 2018)
15-76009215-G-A		not specified	Uncertain significance (Apr 18, 2023)
15-76009236-C-A		not specified	Uncertain significance (Jul 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NRG4	protein_coding	protein_coding	ENST00000394907	5	123827

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0280	0.811	125683	1	50	125734	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.406	54	63.1	0.856	0.00000313	760
Missense in Polyphen		15	19.148	0.78338		252
Synonymous	0.283	22	23.8	0.926	0.00000136	211
Loss of Function	1.07	3	5.78	0.519	2.43e-7	76

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000882	0.0000879
Middle Eastern	0.000111	0.000109
South Asian	0.00112	0.00108
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Low affinity ligand for the ERBB4 tyrosine kinase receptor. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. Does not bind to the ERBB1, ERBB2 and ERBB3 receptors (By similarity). {ECO:0000250}.
• Pathway: ErbB signaling pathway - Homo sapiens (human);EGF-Core;ErbB Signaling Pathway;SHC1 events in ERBB2 signaling;Signaling by PTK6;Disease;Signal Transduction;g-secretase mediated erbb4 signaling pathway;ERBB2 Activates PTK6 Signaling;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;GPCR signaling-G alpha s Epac and ERK;Downregulation of ERBB2 signaling;GPCR signaling-G alpha s PKA and ERK;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;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: 0.0813

Intolerance Scores

• loftool: 0.701
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.57

Haploinsufficiency Scores

• pHI: 0.0675
• hipred: N
• hipred_score: 0.307
• ghis: 0.469

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.368

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nrg4
• Phenotype: normal phenotype

Gene ontology

• Biological process: MAPK cascade;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;protein binding;growth factor activity;phosphatidylinositol-4,5-bisphosphate 3-kinase activity