• 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)
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)