NGEF
protein-codingneuronal guanine nucleotide exchange factor, the group of Dbl family Rho GEFs
Gene summary
Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in ephrin receptor signaling pathway; negative regulation of dendritic spine morphogenesis; and regulation of actin cytoskeleton organization. Predicted to be located in cytosol. Predicted to be active in postsynapse. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~134.6 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 NGEF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_019850.3. 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 | 1 | 1 | 2 | |||
| missense | 69 | 6 | 75 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 70 | 7 | 1 | 78 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_062824.2 | 14 | MANE Select | |
| Ensembl | ENSP00000264051.3 | 14 | MANE Select | |
| RefSeq | NP_001107562.1 | 13 | Standard | |
| Ensembl | ENSP00000362653.4 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Developmental Biology
- Signaling by GPCR
- Signal Transduction
- EPH-Ephrin signaling
Biological Process
- G protein-coupled receptor signaling pathway
- regulation of Rho protein signal transduction
- positive regulation of apoptotic process
- regulation of GTPase activity
- ephrin receptor signaling pathway
Molecular Function
- guanyl-nucleotide exchange factor activity
- Rho guanyl-nucleotide exchange factor activity
Cellular Component
- cytosol
- membrane
- growth cone
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264051
- Coding exons
- 14
- Length
- 134587
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.66 | 335 | 432 | 0.775 | 0.0000270 | 4687 |
| Missense (PolyPhen) | 107 | 178.83 | 0.59832 | 1821 | ||
| Synonymous | -0.00816 | 181 | 181 | 1.00 | 0.0000120 | 1343 |
| Loss of Function | 4.31 | 7 | 34.2 | 0.205 | 0.00000153 | 402 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a guanine nucleotide exchange factor (GEF) which differentially activates the GTPases RHOA, RAC1 and CDC42. Plays a role in axon guidance regulating ephrin-induced growth cone collapse and dendritic spine morphogenesis. Upon activation by ephrin through EPHA4, the GEF activity switches toward RHOA resulting in its activation. Activated RHOA promotes cone retraction at the expense of RAC1- and CDC42-stimulated growth cone extension (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- LoFtool
- 0.462
- RVIS EVS
- -0.33
- RVIS percentile EVS
- 30.82
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.850
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |