CHI3L1
protein-codingchitinase 3 like 1, the group of Chitinases
Gene summary
Chitinases catalyze the hydrolysis of chitin, which is an abundant glycopolymer found in insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 family of chitinases includes eight human family members. This gene encodes a glycoprotein member of the glycosyl hydrolase 18 family. The protein lacks chitinase activity and is secreted by activated macrophages, chondrocytes, neutrophils and synovial cells. The protein is thought to play a role in the process of inflammation and tissue remodeling. [provided by RefSeq, Sep 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0005090
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CHI3L1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001276.4. 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 | 1 | 1 | 2 | 4 | ||
| missense | 82 | 2 | 84 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 89 | 3 | 2 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001267.2 | 10 | MANE Select | |
| Ensembl | ENSP00000255409.3 | 10 | MANE Select | |
| Ensembl | ENSP00000385350.2 | 4 | Standard | |
| Ensembl | ENSP00000544833.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Mammary gland development pathway - Involution (Stage 4 of 4)
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- carbohydrate metabolic process
- apoptotic process
- inflammatory response
- activation of NF-kappaB-inducing kinase activity
- response to mechanical stimulus
Molecular Function
- chitinase activity
- extracellular matrix structural constituent
- protein binding
- chitin binding
- carbohydrate binding
Cellular Component
- extracellular region
- extracellular space
- cytoplasm
- endoplasmic reticulum
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000255409
- Coding exons
- 10
- Length
- 7819
- Individuals with no LoFs
- 125678
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 70
- Defined
- 125748
- p
- 0.000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.579 | 253 | 228 | 1.11 | 0.0000134 | 2514 |
| Missense (PolyPhen) | 86 | 80.826 | 1.064 | 1006 | ||
| Synonymous | -1.28 | 109 | 93.2 | 1.17 | 0.00000608 | 749 |
| Loss of Function | 1.82 | 11 | 19.7 | 0.558 | 9.27e-7 | 223 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0026 | 0.0026 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00019 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their environment. Plays a role in T-helper cell type 2 (Th2) inflammatory response and IL-13-induced inflammation, regulating allergen sensitization, inflammatory cell apoptosis, dendritic cell accumulation and M2 macrophage differentiation. Facilitates invasion of pathogenic enteric bacteria into colonic mucosa and lymphoid organs. Mediates activation of AKT1 signaling pathway and subsequent IL8 production in colonic epithelial cells. Regulates antibacterial responses in lung by contributing to macrophage bacterial killing, controlling bacterial dissemination and augmenting host tolerance. Also regulates hyperoxia-induced injury, inflammation and epithelial apoptosis in lung. {ECO:0000269|PubMed:16472595, ECO:0000269|PubMed:19414556, ECO:0000269|PubMed:20558631, ECO:0000269|PubMed:9492324}.;
- Disease
- DISEASE: Asthma-related traits 7 (ASRT7) [MIM:611960]: Asthma- related traits include clinical symptoms of asthma, such as coughing, wheezing, dyspnea, bronchial hyperresponsiveness as assessed by methacholine challenge test, serum IgE levels, atopy and atopic dermatitis. {ECO:0000269|PubMed:18403759}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:17160890, ECO:0000269|PubMed:20051317}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.349
Intolerance Scores
- LoFtool
- 0.727
- RVIS EVS
- -0.13
- RVIS percentile EVS
- 43.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.563
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | Medium | High |