NRG4
protein-codingneuregulin 4, the group of Neuregulins
Gene summary
The neuregulins, including NRG4, activate type-1 growth factor receptors (see EGFR; MIM 131550) to initiating cell-to-cell signaling through tyrosine phosphorylation (Harari et al., 1999 [PubMed 10348342]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~123.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NRG4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_138573.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 18 | 1 | 19 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 18 | 0 | 1 | 19 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_612640.1 | 5 | MANE Select | |
| Ensembl | ENSP00000378367.3 | 5 | MANE Select | |
| Ensembl | ENSP00000431810.1 | 3 | Standard | |
| Ensembl | ENSP00000432751.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- ErbB signaling pathway - Homo sapiens (human)
- EGF-Core
- ErbB Signaling Pathway
- SHC1 events in ERBB2 signaling
- Signaling by PTK6
Biological Process
- MAPK cascade
- nervous system development
- regulation of signaling receptor activity
- peptidyl-tyrosine phosphorylation
- intracellular signal transduction
Molecular Function
- protein tyrosine kinase activity
- Ras guanyl-nucleotide exchange factor activity
- signaling receptor binding
- protein binding
- growth factor activity
Cellular Component
- extracellular region
- extracellular space
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394907
- Coding exons
- 5
- Length
- 123827
- Individuals with no LoFs
- 125683
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 50
- Defined
- 125734
- p
- 0.000203
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.406 | 54 | 63.1 | 0.856 | 0.00000313 | 760 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000088 | 0.000088 | rare |
| South Asian | 0.0011 | 0.0011 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.0813
Intolerance Scores
- LoFtool
- 0.701
- RVIS EVS
- 0.19
- RVIS percentile EVS
- 66.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.368
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |