CNKSR2 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- CNKSR2 (HGNC:19701) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- connector enhancer of kinase suppressor of Ras 2
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- KIAA0902, CNK2, KSR2
- %HI
- 7.56(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.19(Read more about gnomAD LOEUF score)
- Cytoband
- Xp22.12
- Genomic Coordinates
-
GRCh37/hg19: chrX:21392536-21672807 NCBI Ensembl UCSC GRCh38/hg38: chrX:21374418-21654689 NCBI Ensembl UCSC - MANE Select Transcript
- NM_014927.5 ENST00000379510.5 (Read more about MANE Select)
- Function
- May function as an adapter protein or regulator of Ras signaling pathways. {ECO:0000269|PubMed:14597674}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- Mental retardation, X-linked, syndromic, Houge type (X-linked recessive) Monarch
-
PUBMED:
22511892
Houge et al. (2012) describes a 5-year-old boy with developmental delay, well-controlled epilepsy, and microcephaly, and a 234-kb deletion of Xp22.12 detected by copy number analysis. The maternally inherited deletion removed the initial 15 of the 21 exons of CNKSR2. This child is further clinically classified as Patient 3 (Norwegian Boy) in Vaags et al. 2014.
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PUBMED:
25223753
Vaags et al. 2014 report 3 additional probands (a total of 7 additional affected individuals from 3 previously unreported families) with deletions or frameshift variants involving CNKSR2. The affected males are characterized by "intellectual disability, attention problems, and abrupt lifelong language loss following a brief early childhood epilepsy with continuous spike-waves in sleep." Two of the new probands discussed in this paper were shown to have deletions involving CNKSR2. The first, a 1.17 Mb deletion "approximated" the RPS6KA3 gene, associated with Coffin-Lowry syndrome. The authors report that fine mapping showed that the deletion does not involve this gene, and that Western blot analysis confirmed typical expression of the RPSKA3 protein product in the proband. The second deletion (0.51 Mb), involving only the CNKSR2 gene. The third family was found to have truncating frameshift variant, p.D152RfsX8. All variants are reportedly inherited from carrier mothers. Detailed descriptions of the methods used to identify these variants is not provided.
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PUBMED:
25754917
Aypar et al. (2015) described a 7-year old non-dysmorphic boy with medically intractable focal seizures and developmental delay. He had a 342 kilobase focal deletion at Xp22.12 which was maternally-inherited from an a mother who is reportedly unaffected. "The minimal deleted interval contains the entire CNKSR2 gene isoforms 3 and 4, and the majority of the CNKSR2 gene isoforms 1 and 2 with the most distal deleted probe located within the last exon of those isoforms. The interval between the most distal deleted probe, 21,670,497, and the most distal normal probe, 21,678,137, contains a hypothetical gene, KLHL34.”
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.