RHBDL2
protein-codingrhomboid like 2, the group of Rhomboid family
Gene summary
The protein encoded by this gene is a member of the rhomboid family of integral membrane proteins. This family contains proteins that are related to Drosophila rhomboid protein. Members of this family are found in both prokaryotes and eukaryotes and are thought to function as intramembrane serine proteases. The encoded protein is thought to release soluble growth factors by proteolytic cleavage of certain membrane-bound substrates, including ephrin B2 and ephrin B3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~56.0 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 RHBDL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017821.5. 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 | 0 | |||||
| missense | 43 | 2 | 45 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 46 | 2 | 0 | 48 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060291.2 | 7 | MANE Select | |
| Ensembl | ENSP00000362081.1 | 7 | MANE Select | |
| RefSeq | NP_001291675.1 | 8 | Standard | |
| Ensembl | ENSP00000289248.2 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- DroToll-like
Biological Process
- proteolysis
Molecular Function
- serine-type endopeptidase activity
Cellular Component
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000289248
- Coding exons
- 7
- Length
- 55993
- Individuals with no LoFs
- 125483
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 262
- Defined
- 125745
- p
- 0.00104
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0707 | 159 | 162 | 0.984 | 0.00000783 | 1991 |
| Missense (PolyPhen) | 39 | 47.562 | 0.81999 | 585 | ||
| Synonymous | 1.41 | 45 | 58.8 | 0.766 | 0.00000304 | 577 |
| Loss of Function | 0.539 | 12 | 14.2 | 0.846 | 6.83e-7 | 183 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.0014 | 0.0014 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00074 | 0.00074 | rare |
| European (Non-Finnish) | 0.0016 | 0.0016 | notable |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. Known substrate: EFNB3. {ECO:0000269|PubMed:11672525, ECO:0000269|PubMed:15047175}.;
Recessive Scores
- pRec
- 0.0856
Intolerance Scores
- LoFtool
- 0.812
- RVIS EVS
- 0.59
- RVIS percentile EVS
- 82.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |