NDRG4
protein-codingNDRG family member 4, the group of NDRG family
Gene summary
This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that is required for cell cycle progression and survival in primary astrocytes and may be involved in the regulation of mitogenic signalling in vascular smooth muscles cells. Alternative splicing results in multiple transcripts encoding different isoforms.[provided by RefSeq, Jun 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~50.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0018852
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NDRG4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001242835.2. 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 | 3 | 7 | 10 | |||
| missense | 48 | 48 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 55 | 7 | 0 | 62 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001229764.1 | 15 | MANE Select | |
| Ensembl | ENSP00000457659.1 | 15 | MANE Select | |
| RefSeq | NP_001123959.1 | 16 | Standard | |
| RefSeq | NP_001229762.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ndrg4 | Danio rerio | Structure: cardiac muscle cell Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- heart looping
- signal transduction
- brain development
- visual learning
- negative regulation of platelet-derived growth factor receptor signaling pathway
Molecular Function
- molecular_function
- protein binding
Cellular Component
- cytoplasm
- mitochondrion
- endoplasmic reticulum membrane
- cytosol
- basolateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394282
- Coding exons
- 16
- Length
- 50783
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125745
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.572 | 207 | 232 | 0.894 | 0.0000140 | 2547 |
| Missense (PolyPhen) | 75 | 81.063 | 0.92521 | 872 | ||
| Synonymous | -0.0884 | 98 | 96.9 | 1.01 | 0.00000637 | 777 |
| Loss of Function | 3.14 | 8 | 24.9 | 0.321 | 0.00000117 | 281 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.000098 | 0.000097 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Contributes to the maintenance of intracerebral BDNF levels within the normal range, which is necessary for the preservation of spatial learning and the resistance to neuronal cell death caused by ischemic stress (By similarity). May enhance growth factor-induced ERK1 and ERK2 phosphorylation, including that induced by PDGF and FGF. May attenuate NGF-promoted ELK1 phosphorylation in a microtubule-dependent manner. {ECO:0000250, ECO:0000269|PubMed:12755708}.;
Recessive Scores
- pRec
- 0.121
Intolerance Scores
- LoFtool
- 0.787
- RVIS EVS
- -0.78
- RVIS percentile EVS
- 12.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.227
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |