NRG3

neuregulin 3, the group of Neuregulins

Basic information

Region (hg38): 10:81875193-82987179

Links

ENSG00000185737 ∙ NCBI:10718 ∙ OMIM:605533 ∙ HGNC:7999 ∙ Uniprot:P56975 ∙ 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 NRG3 gene.

• Inborn genetic diseases (27 variants)
• not provided (9 variants)
• Aganglionic megacolon (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NRG3 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				1	4	5
missense			27	1	3	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	27	2	7

Variants in NRG3

This is a list of pathogenic ClinVar variants found in the NRG3 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-81875413-A-T		not specified	Uncertain significance (Aug 04, 2021)
10-81875426-C-A		not specified	Uncertain significance (Mar 01, 2023)
10-81875485-C-T		not specified	Uncertain significance (Dec 16, 2023)
10-81875492-A-T		not specified	Uncertain significance (Aug 04, 2023)
10-81875515-G-A		not specified	Uncertain significance (Jun 01, 2023)
10-81875624-A-G		not specified	Uncertain significance (Dec 05, 2022)
10-81875637-C-T			Benign (Mar 29, 2018)
10-81875651-A-G		not specified	Uncertain significance (Feb 05, 2024)
10-81875663-T-G		not specified	Uncertain significance (Apr 06, 2022)
10-81875732-C-G		not specified	Uncertain significance (May 09, 2022)
10-81875865-C-G		not specified	Uncertain significance (Aug 02, 2021)
10-81875891-C-T		not specified	Uncertain significance (Aug 29, 2022)
10-81875893-C-G		not specified	Uncertain significance (Aug 17, 2022)
10-81875974-G-C		not specified	Uncertain significance (Apr 07, 2023)
10-81875981-G-A		not specified	Uncertain significance (Nov 08, 2022)
10-81876001-A-G		not specified	Uncertain significance (Oct 12, 2021)
10-81876028-G-T		not specified	Uncertain significance (Oct 18, 2021)
10-81876031-A-G		not specified	Uncertain significance (Oct 26, 2021)
10-81876041-A-T		not specified	Uncertain significance (Apr 07, 2023)
10-81876042-C-T			Benign (Jul 19, 2018)
10-81876058-C-G		not specified	Uncertain significance (Nov 18, 2022)
10-81876136-C-G		not specified	Uncertain significance (Jan 29, 2024)
10-81878019-C-G		Aganglionic megacolon	Uncertain significance (May 16, 2019)
10-82358744-A-G		not specified	Uncertain significance (Feb 08, 2023)
10-82358754-C-T		not specified	Uncertain significance (Feb 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NRG3	protein_coding	protein_coding	ENST00000372141	9	1111866

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.109	0.891	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.257	385	371	1.04	0.0000187	4473
Missense in Polyphen		124	152.48	0.81323		1770
Synonymous	-1.04	171	155	1.11	0.00000833	1464
Loss of Function	3.85	8	31.2	0.256	0.00000189	329

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000340	0.000337
Ashkenazi Jewish	0.00199	0.00199
East Asian	0.000164	0.000163
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000247	0.000246
Middle Eastern	0.000164	0.000163
South Asian	0.000261	0.000261
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Direct ligand for the ERBB4 tyrosine kinase receptor. Binding results in ligand-stimulated tyrosine phosphorylation and activation of the receptor. Does not bind to the EGF receptor, ERBB2 or ERBB3 receptors. May be a survival factor for oligodendrocytes. {ECO:0000269|PubMed:16478787, ECO:0000269|PubMed:9275162}.
• 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;GPCR signaling-G alpha s Epac and ERK;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;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: 0.103

Intolerance Scores

• loftool: 0.580
• rvis_EVS: -0.46
• rvis_percentile_EVS: 23.57

Haploinsufficiency Scores

• pHI: 0.157
• hipred: Y
• hipred_score: 0.655
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.639

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nrg3
• Phenotype: endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of cell growth;activation of transmembrane receptor protein tyrosine kinase activity;pattern specification process;regulation of signaling receptor activity;chemorepulsion involved in interneuron migration from the subpallium to the cortex;intracellular signal transduction;modulation of chemical synaptic transmission;mammary placode formation;negative regulation of neuron migration
• Cellular component: extracellular region;extracellular space;integral component of plasma membrane;glutamatergic synapse
• Molecular function: signaling receptor binding;growth factor activity;transmembrane receptor protein tyrosine kinase activator activity;receptor tyrosine kinase binding;chemorepellent activity