RIPPLY2
protein-codingripply transcriptional repressor 2
Gene summary
This gene encodes a nuclear protein that belongs to a novel family of proteins required for vertebrate somitogenesis. Members of this family have a tetrapeptide WRPW motif that is required for interaction with the transcriptional repressor Groucho and a carboxy-terminal Ripply homology domain/Bowline-DSCR-Ledgerline conserved region required for transcriptional repression. Null mutant mice die soon after birth and display defects in axial skeleton segmentation due to defective somitogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
- C6orf159
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014694
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0014694
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014694
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0010180
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014694
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RIPPLY2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001009994.3. 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 | 18 | 1 | 20 | ||
| missense | 46 | 2 | 48 | |||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 3 | |||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 2 | 54 | 20 | 1 | 77 |
Highest pathogenic variant AF is 0.0001722749
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001009994.1 | 4 | MANE Select | |
| Ensembl | ENSP00000358703.1 | 4 | MANE Select | |
| RefSeq | NP_001387828.1 | 2 | Standard | |
| RefSeq | NP_001387829.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene regulatory network modelling somitogenesis
Biological Process
- negative regulation of transcription by RNA polymerase II
- ossification
- somitogenesis
- Notch signaling pathway
- determination of left/right symmetry
Molecular Function
- protein binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369689
- Coding exons
- 4
- Length
- 4250
- Individuals with no LoFs
- 125687
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125719
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.555 | 82 | 69.0 | 1.19 | 0.00000314 | 817 |
| Missense (PolyPhen) | 25 | 20.427 | 1.2239 | 286 | ||
| Synonymous | 0.941 | 21 | 27.2 | 0.771 | 0.00000137 | 230 |
| Loss of Function | 1.11 | 4 | 7.22 | 0.554 | 3.05e-7 | 91 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00027 | 0.00027 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in somitogenesis. Required for somite segregation and establishment of rostrocaudal polarity in somites (By similarity). {ECO:0000250|UniProtKB:Q2WG76}.;
- Disease
- DISEASE: Spondylocostal dysostosis 6, autosomal recessive (SCDO6) [MIM:616566]: A form of spondylocostal dysostosis, a condition of variable severity associated with vertebral and rib segmentation defects. The main skeletal malformations include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and other rib malformations. Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the malformation and leads to a dwarf-like appearance. As the thorax is small, infants frequently have respiratory insufficiency and repeated respiratory infections resulting in life-threatening complications in the first year of life. {ECO:0000269|PubMed:25343988}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.419
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.231
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |