CRLF2
protein-codingcytokine receptor like factor 2, the group of Fibronectin type III domain containing|Pseudoautosomal region 1
Gene summary
This gene encodes a member of the type I cytokine receptor family. The encoded protein is a receptor for thymic stromal lymphopoietin (TSLP). Together with the interleukin 7 receptor (IL7R), the encoded protein and TSLP activate STAT3, STAT5, and JAK2 pathways, which control processes such as cell proliferation and development of the hematopoietic system. Rearrangement of this gene with immunoglobulin heavy chain gene (IGH) on chromosome 14, or with P2Y purinoceptor 8 gene (P2RY8) on the same X or Y chromosomes is associated with B-progenitor acute lymphoblastic leukemia (ALL) and Down syndrome ALL. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.2 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 CRLF2 variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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 | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 0 | 0 | 0 | 0 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| Ensembl | ENSP00000383641.3 | 8 | MANE Select | |
| RefSeq | NP_001012288.2 | 12 | Standard | |
| RefSeq | NP_071431.2 | 16 | Standard | |
| Ensembl | ENSP00000370979.4 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Jak-STAT signaling pathway - Homo sapiens (human)
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- JAK-STAT-Core
- Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway
Biological Process
- positive regulation of cell population proliferation
- cytokine-mediated signaling pathway
- positive regulation of mast cell activation
- interleukin-7-mediated signaling pathway
- positive regulation of STAT cascade
Molecular Function
- cytokine receptor activity
- cytokine binding
Cellular Component
- extracellular region
- plasma membrane
- external side of plasma membrane
- integral component of membrane
- receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381567
- Coding exons
- 6
- Length
- 16727
- Individuals with no LoFs
- 124338
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 150
- Defined
- 124488
- p
- 0.000603
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.853 | 178 | 149 | 1.20 | 0.00000809 | 1658 |
| Missense (PolyPhen) | 51 | 40.385 | 1.2628 | 495 | ||
| Synonymous | -1.07 | 75 | 64.1 | 1.17 | 0.00000418 | 489 |
| Loss of Function | 0.520 | 11 | 13.0 | 0.845 | 5.64e-7 | 136 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00019 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0.0011 | 0.0011 | notable |
| East Asian | 0.00045 | 0.00045 | rare |
| Finnish | 0.00060 | 0.00060 | rare |
| European (Non-Finnish) | 0.00090 | 0.00090 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00050 | 0.00050 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5. Also activates JAK2 (By similarity). Implicated in the development of the hematopoietic system. {ECO:0000250, ECO:0000269|PubMed:11418668}.;
Essentials
- Indispensability pred.
- E
- Indispensability score
- 0.754
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |