CHRD
protein-codingchordin, the group of Chordin family
Gene summary
This gene encodes a secreted protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta-like bone morphogenetic proteins and sequestering them in latent complexes. The encoded protein may also have roles in organogenesis and during adulthood. It has been suggested that this gene could be a candidate gene for Cornelia de Lange syndrome. Reduced expression of this gene results in enhanced bone regeneration. Alternative splicing results in multiple transcript variants. Other alternative splice variants have been described but their full length sequence has not been determined. [provided by RefSeq, Jan 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005453
Submitter: ClinGen
*CHRD* was first reported in relation to autosomal recessive congenital heart disease in 2016 (Priest et al. 2016; PMID: 27058611). Two missense variants that have been reported in one proband in one publication (PMID: 27058611) are included in this curation. The mechanism of pathogenicity is unknown. This gene-disease relationship is also supported by biochemical function evidence (PMID: 15254540). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date October 17th, 2023 (SOP Version 9).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CHRD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003741.4. 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 | 3 | 3 | 10 | ||
| missense | 158 | 9 | 1 | 168 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 171 | 12 | 4 | 187 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003732.2 | 23 | MANE Select | |
| Ensembl | ENSP00000204604.1 | 23 | MANE Select | |
| RefSeq | NP_001291401.1 | 23 | Standard | |
| RefSeq | NP_001291402.1 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| chrd | Danio rerio | Structure: primordial germ cell Quality: mislocalised abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TGF-beta signaling pathway - Homo sapiens (human)
- Mesodermal Commitment Pathway
- alk in cardiac myocytes
- BMP receptor signaling
Biological Process
- skeletal system development
- osteoblast differentiation
- gastrulation with mouth forming second
- mesoderm formation
- positive regulation of mesenchymal cell proliferation
Molecular Function
- protein binding
- heparin binding
- cytokine binding
- syndecan binding
Cellular Component
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000204604
- Coding exons
- 23
- Length
- 10664
- Individuals with no LoFs
- 125705
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 43
- Defined
- 125748
- p
- 0.000171
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.46 | 462 | 559 | 0.826 | 0.0000335 | 5937 |
| Missense (PolyPhen) | 206 | 258.78 | 0.79604 | 2724 | ||
| Synonymous | -0.333 | 239 | 233 | 1.03 | 0.0000134 | 2088 |
| Loss of Function | 4.26 | 17 | 49.3 | 0.345 | 0.00000272 | 511 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00025 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0.00080 | 0.00079 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00031 | 0.00028 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Dorsalizing factor. Key developmental protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta family bone morphogenetic proteins (BMPs) and sequestering them in latent complexes (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.358
Intolerance Scores
- LoFtool
- 0.715
- RVIS EVS
- -0.68
- RVIS percentile EVS
- 15.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.661
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |