CRKL |
- 1
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- CRKL (HGNC:2363) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- CRK like proto-oncogene, adaptor protein
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- No aliases found
- %HI
- 4.35(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.45(Read more about gnomAD pLI score)
- LOEUF
- 0.64(Read more about gnomAD LOEUF score)
- Cytoband
- 22q11.21
- Genomic Coordinates
-
GRCh37/hg19: chr22:21271695-21308035 NCBI Ensembl UCSC GRCh38/hg38: chr22:20917407-20953747 NCBI Ensembl UCSC - MANE Select Transcript
- NM_005207.4 ENST00000354336.8 (Read more about MANE Select)
- Function
- May mediate the transduction of intracellular signals. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-2553
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency
(1)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Related Links:
Last Evaluated:
04/13/2020
Haploinsufficiency (HI) Score Details
HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency
(Disclaimer)
HI Evidence:
-
PUBMED:
28121514
Lopez-Rivera et al. (2017) report sequence level variants in five individuals with renal agenesis or hypodysplasia. One of these variants was a nonsense variant (c.91C>T; NM_005207.3), which resulted in a premature termination of the transcript. The other four were missense variants that are evolutionarily conserved and rare/absent in control databases. Inheritance testing was not noted for these variants. Functional studies using a mouse knockout model was consistent with the CRKL gene being involved in renal development, with knockout mice showing developmental anomalies in the kidney and urinary tract including hydronephrosis. Of note, this paper also reported several patients with non-focal deletions overlapping the CRKL gene, who also had renal abnormalities.
HI Evidence Comments:
CRKL lies within the common 22q11.2 deletion syndrome region. Observations in mouse models have led to the hypothesis that haploinsufficiency of CRKL contributes to the 22q11.2 phenotype, particularly in regards to cardiovascular and genitourinary defects (PMID:16399079; 28121514). The single reported loss-of-function type variant (nonsense) in CRKL was identified in a patient who presented with renal hypodysplasia. Four additional missense variants have also been reported, but there is insufficient evidence to support that these are clinically causative, would result in a loss of CRKL protein function, or would be equivalent to loss of the entire copy of CRKL.
Given the limited number of reported variants affecting the CRKL gene, the haploinsufficiency score for this gene is a 1.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Focal duplications involving only CRKL have not been reported in the literature; therefore, the triplosensitivity score for this gene is a 0.
Genomic View
Select assembly:
(NC_000022.10)
(NC_000022.11)