CRLF3
protein-codingcytokine receptor like factor 3, the group of Fibronectin type III domain containing
Gene summary
This gene encodes a cytokine receptor-like factor that may negatively regulate cell cycle progression at the G0/G1 phase. Studies of the related rat protein suggest that it may regulate neuronal morphology and synaptic vesicle biogenesis. This gene is one of several genes located in the neurofibromatosis type I tumor suppressor region on the q arm of chromosome 17, a region that is subject to microdeletions, duplications, chromosomal breaks and rearrangements. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 2 and 5. [provided by RefSeq, Aug 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~55.3 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 CRLF3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015986.4. 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 | ||||
| missense | 43 | 1 | 44 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 44 | 1 | 0 | 45 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057070.3 | 8 | MANE Select | |
| Ensembl | ENSP00000318804.6 | 8 | MANE Select | |
| Ensembl | ENSP00000462643.1 | 3 | Standard | |
| Ensembl | ENSP00000463689.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- G1/S transition of mitotic cell cycle
- negative regulation of cell growth
- positive regulation of transcription, DNA-templated
- positive regulation of transcription by RNA polymerase II
- positive regulation of JAK-STAT cascade
Molecular Function
- DNA binding
- protein binding
- identical protein binding
Cellular Component
- nucleus
- cytoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000324238
- Coding exons
- 8
- Length
- 55389
- Individuals with no LoFs
- 125684
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 64
- Defined
- 125748
- p
- 0.000255
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.12 | 195 | 244 | 0.798 | 0.0000125 | 2870 |
| Missense (PolyPhen) | 59 | 87.224 | 0.67642 | 1064 | ||
| Synonymous | -0.977 | 104 | 92.1 | 1.13 | 0.00000487 | 868 |
| Loss of Function | 2.81 | 10 | 25.2 | 0.397 | 0.00000156 | 256 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00087 | 0.00087 | rare |
| Finnish | 0.00095 | 0.00069 | rare |
| European (Non-Finnish) | 0.00020 | 0.00018 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a role in the negative regulation of cell cycle progression. {ECO:0000269|PubMed:19427400}.;
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- LoFtool
- 0.612
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.521
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |