RALBP1
protein-codingralA binding protein 1
Gene summary
RALBP1 plays a role in receptor-mediated endocytosis and is a downstream effector of the small GTP-binding protein RAL (see RALA; MIM 179550). Small G proteins, such as RAL, have GDP-bound inactive and GTP-bound active forms, which shift from the inactive to the active state through the action of RALGDS (MIM 601619), which in turn is activated by RAS (see HRAS; MIM 190020) (summary by Feig, 2003 [PubMed 12888294]).[supplied by OMIM, Nov 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~63.1 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 RALBP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006788.4. 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 | 4 | 4 | ||||
| missense | 80 | 3 | 2 | 85 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 81 | 7 | 2 | 90 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006779.1 | 9 | MANE Select | |
| Ensembl | ENSP00000372924.3 | 9 | MANE Select | |
| Ensembl | ENSP00000019317.4 | 9 | Standard | |
| Ensembl | ENSP00000019317.4 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Doxorubicin Pathway (Cancer Cell), Pharmacodynamics
- Ras signaling pathway - Homo sapiens (human)
- Doxorubicin Pathway, Pharmacokinetics
- Pathways in cancer - Homo sapiens (human)
- Carbamazepine Pathway, Pharmacokinetics
Biological Process
- drug transmembrane transport
- endocytosis
- chemotaxis
- signal transduction
- small GTPase mediated signal transduction
Molecular Function
- GTPase activator activity
- protein binding
- drug transmembrane transporter activity
- Ral GTPase binding
- transmembrane transporter activity
Cellular Component
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000019317
- Coding exons
- 9
- Length
- 63108
- Individuals with no LoFs
- 125719
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 29
- Defined
- 125748
- p
- 0.000115
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.01 | 254 | 361 | 0.703 | 0.0000204 | 4341 |
| Missense (PolyPhen) | 42 | 83.523 | 0.50285 | 1220 | ||
| Synonymous | 0.485 | 129 | 136 | 0.947 | 0.00000815 | 1180 |
| Loss of Function | 3.94 | 8 | 32.1 | 0.249 | 0.00000182 | 393 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00014 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00049 | 0.00046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00013 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Can activate specifically hydrolysis of GTP bound to RAC1 and CDC42, but not RALA. Mediates ATP-dependent transport of S-(2,4-dinitrophenyl)-glutathione (DNP-SG) and doxorubicin (DOX) and is the major ATP-dependent transporter of glutathione conjugates of electrophiles (GS-E) and DOX in erythrocytes. Can catalyze transport of glutathione conjugates and xenobiotics, and may contribute to the multidrug resistance phenomenon. Serves as a scaffold protein that brings together proteins forming an endocytotic complex during interphase and also with CDK1 to switch off endocytosis, One of its substrates would be EPN1/Epsin. {ECO:0000269|PubMed:11437348, ECO:0000269|PubMed:12775724, ECO:0000269|PubMed:7673236}.;
Recessive Scores
- pRec
- 0.171
Intolerance Scores
- LoFtool
- 0.390
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.935
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |