CSRP1
protein-codingcysteine and glycine rich protein 1, the group of LIM domain containing
Gene summary
This gene encodes a member of the cysteine-rich protein (CSRP) family. This gene family includes a group of LIM domain proteins, which may be involved in regulatory processes important for development and cellular differentiation. The LIM/double zinc-finger motif found in this gene product occurs in proteins with critical functions in gene regulation, cell growth, and somatic differentiation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]
- CYRP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005453
Submitter: ClinGen
*CSRP1* was first reported in relation to autosomal dominant congenital heart disease in 2017 (Kamar et al., PMID: 29326753). One variant (frameshift) that has been reported in three affected probands from one family in one publication (PMIDs: 29326753) is included in this curation. This variant was not scored due to assertion for digenic inheritance with *TRPS1*. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is supported by experimental evidence (expression-level evidence; Descartes fetal expression data, PMID: 17592114). Expression-level evidence in zebrafish with knockdown of CSRP1 is indicative of cardiac bifida. In summary, the evidence supporting the relationship between *CSRP1 *and autosomal dominant Congenital Heart Disease has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role CSRP1 plays in this disease. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date July 2nd 2024 (SOP Version 10).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CSRP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004078.3. 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 | 4 | 1 | 2 | 7 | ||
| missense | 36 | 1 | 37 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 41 | 1 | 3 | 45 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004069.1 | 5 | MANE Select | |
| Ensembl | ENSP00000345079.2 | 5 | MANE Select | |
| RefSeq | NP_001180499.1 | 5 | Standard | |
| RefSeq | NP_001180500.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| csrp1a | Danio rerio | Structure: post-vent region Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in adipocytes - TarBase
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in leukocytes - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
Biological Process
- platelet aggregation
Molecular Function
- RNA binding
- zinc ion binding
Cellular Component
- nucleus
- focal adhesion
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367306
- Coding exons
- 5
- Length
- 25927
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 25
- Defined
- 125748
- p
- 0.0000994
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.215 | 107 | 113 | 0.943 | 0.00000613 | 1253 |
| Missense (PolyPhen) | 35 | 42.288 | 0.82766 | 471 | ||
| Synonymous | 0.510 | 43 | 47.5 | 0.906 | 0.00000295 | 365 |
| Loss of Function | 1.23 | 7 | 11.5 | 0.609 | 6.38e-7 | 131 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Could play a role in neuronal development.;
Recessive Scores
- pRec
- 0.133
Intolerance Scores
- LoFtool
- 0.261
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 67.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.981
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |