FRMD4B
protein-codingFERM domain containing 4B, the group of FERM domain containing
Gene summary
This gene encodes a GRP1-binding protein which contains a FERM protein interaction domain as well as two coiled coil domains. This protein may play a role as a scaffolding protein. [provided by RefSeq, Mar 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~373.8 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 FRMD4B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015123.3. 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 | 162 | 6 | 168 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 168 | 7 | 0 | 175 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055938.2 | 23 | MANE Select | |
| Ensembl | ENSP00000381549.3 | 23 | MANE Select | |
| Ensembl | ENSP00000417550.1 | 4 | Standard | |
| Ensembl | ENSP00000418023.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- establishment of epithelial cell polarity
Cellular Component
- ruffle
- extracellular space
- cytoplasm
- cytoskeleton
- adherens junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398540
- Coding exons
- 23
- Length
- 372594
- Individuals with no LoFs
- 124618
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 124637
- p
- 0.0000762
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0405 | 547 | 544 | 1.00 | 0.0000292 | 6671 |
| Missense (PolyPhen) | 224 | 229.02 | 0.97808 | 2733 | ||
| Synonymous | -0.402 | 220 | 213 | 1.04 | 0.0000121 | 1924 |
| Loss of Function | 5.71 | 14 | 62.8 | 0.223 | 0.00000360 | 729 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000057 | 0.000056 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000082 | 0.000080 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.00019 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Member of GRP1 signaling complexes that are acutely recruited to plasma membrane ruffles in response to insulin receptor signaling. May function as a scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex. Plays a redundant role with FRMD4A in epithelial polarization. {ECO:0000250|UniProtKB:Q920B0}.;
Recessive Scores
- pRec
- 0.100
Intolerance Scores
- LoFtool
- 0.114
- RVIS EVS
- 0.86
- RVIS percentile EVS
- 88.52
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.152
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |