CNKSR1

connector enhancer of kinase suppressor of Ras 1, the group of Sterile alpha motif domain containing|Pleckstrin homology domain containing|PDZ domain containing

Basic information

Region (hg38): 1:26177484-26189884

Links

ENSG00000142675 ∙ NCBI:10256 ∙ OMIM:603272 ∙ HGNC:19700 ∙ Uniprot:Q969H4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNKSR1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNKSR1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	4	7
missense			27	8	6	41
nonsense			2	1		3
start loss						0
frameshift					1	1
inframe indel						0
splice donor/acceptor (+/-2bp)				1		1
splice region				1		1
non coding					2	2
Total	0	0	29	13	13

Variants in CNKSR1

This is a list of pathogenic ClinVar variants found in the CNKSR1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-26177556-G-A			Benign (Apr 10, 2018)
1-26177576-G-C		not specified	Uncertain significance (May 31, 2023)
1-26177584-G-A		not specified	Uncertain significance (Jun 11, 2021)
1-26180481-C-A			Likely benign (Feb 01, 2018)
1-26180493-G-A			Uncertain significance (Jul 01, 2022)
1-26180587-G-A		not specified	Uncertain significance (Nov 14, 2023)
1-26180741-G-A			Benign (Dec 31, 2019)
1-26180761-T-C		not specified	Uncertain significance (Mar 29, 2023)
1-26180836-T-A		not specified	Uncertain significance (Aug 01, 2024)
1-26181848-C-T			Benign (Dec 31, 2019)
1-26181861-C-T		not specified	Uncertain significance (Jun 07, 2023)
1-26181903-C-T			Uncertain significance (Sep 07, 2021)
1-26181931-T-G		not specified	Uncertain significance (Jan 23, 2024)
1-26182386-G-T		Neurodevelopmental disorder	Uncertain significance (Oct 19, 2020)
1-26182555-C-T		not specified	Uncertain significance (Aug 08, 2022)
1-26182558-G-A			Likely benign (Dec 31, 2019)
1-26183209-C-G		not specified	Uncertain significance (May 30, 2024)
1-26183231-A-G		not specified	Uncertain significance (Dec 27, 2023)
1-26183245-G-C		not specified	Uncertain significance (Jun 10, 2022)
1-26183403-G-A		not specified	Uncertain significance (May 20, 2024)
1-26183741-C-T		not specified	Uncertain significance (Jun 02, 2023)
1-26183750-A-G		not specified	Likely benign (Oct 20, 2023)
1-26183819-AC-A		not specified • Usher syndrome type 2C	Benign (Dec 06, 2018)
1-26183826-C-G			Benign/Likely benign (Feb 01, 2023)
1-26184096-C-T		not specified	Uncertain significance (Aug 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNKSR1	protein_coding	protein_coding	ENST00000361530	21	12484

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.29e-30	0.0000636	116638	222	8888	125748	0.0369

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.569	376	408	0.921	0.0000259	4550
Missense in Polyphen		117	130.5	0.89655		1495
Synonymous	0.0271	168	168	0.997	0.0000102	1482
Loss of Function	0.0000730	45	45.0	1.00	0.00000264	456

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0395	0.0396
Ashkenazi Jewish	0.0189	0.0188
East Asian	0.00273	0.00272
Finnish	0.0410	0.0406
European (Non-Finnish)	0.0558	0.0542
Middle Eastern	0.00273	0.00272
South Asian	0.0285	0.0281
Other	0.0448	0.0435

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as an adapter protein or regulator of Ras signaling pathways.
• Pathway: EGF-Ncore;MAP2K and MAPK activation;Disease;Signal Transduction;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;IL3-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.984
• rvis_EVS: 0.52
• rvis_percentile_EVS: 80.34

Haploinsufficiency Scores

• pHI: 0.166
• hipred: N
• hipred_score: 0.337
• ghis: 0.450

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.814

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cnksr1

Gene ontology

• Biological process: transmembrane receptor protein tyrosine kinase signaling pathway;Ras protein signal transduction;Rho protein signal transduction
• Cellular component: plasma membrane;cell-cell junction;cell cortex
• Molecular function: protein binding;protein binding, bridging