RAPGEF6
protein-codingRap guanine nucleotide exchange factor 6, the group of PDZ domain containing
Gene summary
Enables several functions, including GTP-dependent protein binding activity; guanyl-nucleotide exchange factor activity; and phosphatidic acid binding activity. Involved in positive regulation of microvillus assembly. Located in apical plasma membrane; cytosol; and endocytic vesicle. [provided by Alliance of Genome Resources, Jun 2026]
- PDZGEF2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~211.3 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 RAPGEF6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016340.6. 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 | 3 | 5 | ||
| missense | 191 | 3 | 1 | 195 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 197 | 4 | 4 | 205 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057424.3 | 28 | MANE Select | |
| Ensembl | ENSP00000421684.1 | 28 | MANE Select | |
| RefSeq | NP_001157858.1 | 29 | Standard | |
| RefSeq | NP_001157859.1 | 29 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tight junction - Homo sapiens (human)
- Rap1 signaling pathway - Homo sapiens (human)
Biological Process
- Ras protein signal transduction
- microvillus assembly
- regulation of GTPase activity
- positive regulation of GTPase activity
- protein localization to plasma membrane
Molecular Function
- guanyl-nucleotide exchange factor activity
- protein binding
- Ras GTPase binding
- GTP-dependent protein binding
- phosphatidic acid binding
Cellular Component
- centrosome
- cytosol
- plasma membrane
- apical plasma membrane
- endocytic vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296859
- Coding exons
- 29
- Length
- 211316
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 125748
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.56 | 723 | 851 | 0.850 | 0.0000428 | 10665 |
| Missense (PolyPhen) | 302 | 417.88 | 0.7227 | 5281 | ||
| Synonymous | -0.763 | 313 | 296 | 1.06 | 0.0000150 | 3000 |
| Loss of Function | 6.74 | 14 | 78.3 | 0.179 | 0.00000409 | 989 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00032 | 0.00032 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Guanine nucleotide exchange factor (GEF) for Rap1A, Rap2A and M-Ras GTPases. Does not interact with cAMP. {ECO:0000269|PubMed:11524421, ECO:0000269|PubMed:12581858}.;
Recessive Scores
- pRec
- 0.0989
Intolerance Scores
- LoFtool
- 0.778
- RVIS EVS
- -1.67
- RVIS percentile EVS
- 2.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.853
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |