CNKSR1 (connector enhancer of kinase suppressor of Ras 1)

Gene

• Entrez ID: 10256
• Gene name: Connector enhancer of kinase suppressor of Ras 1
• Gene symbol: CNKSR1
• Synonyms (NCBI Gene): CNK, CNK1
• Chromosome: 1
• Chromosome location: 1p36.11
• Summary: This gene encodes a protein containing several motifs involved in protein-protein interaction, including PDZ, PH (Pleckstrin homology), and SAM (sterile alpha motif) domains. The encoded protein acts as a scaffold component for receptor tyrosine kinase si

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2202643	hsa-miR-182	CLIP-seq
MIRT2202644	hsa-miR-31	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	15231748, 16189514, 25416956, 28514442, 31515488, 32296183, 33961781, 35512704
GO:0005737	Component	Cytoplasm	IEA
GO:0005886	Component	Plasma membrane	TAS	9814705
GO:0005911	Component	Cell-cell junction	TAS	9814705
GO:0005938	Component	Cell cortex	IDA	15075335
GO:0007169	Process	Cell surface receptor protein tyrosine kinase signaling pathway	TAS	9814705
GO:0016020	Component	Membrane	IEA
GO:0030674	Function	Protein-macromolecule adaptor activity	IDA	14749388

Other IDs

• MIM: 603272
• HGNC: 19700
• e!Ensembl: ENSG00000142675

Protein

• UniProt ID: Q969H4
• Protein name: Connector enhancer of kinase suppressor of ras 1 (Connector enhancer of KSR 1) (CNK homolog protein 1) (CNK1) (hCNK1) (Connector enhancer of KSR-like)
• Protein function: May function as an adapter protein or regulator of Ras signaling pathways.
• PDB: 1WWV
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00536	SAM_1	5 → 68	SAM domain (Sterile alpha motif)	Domain
  PF10534	CRIC_ras_sig	78 → 162	Connector enhancer of kinase suppressor of ras	Domain
  PF00169	PH	404 → 502	PH domain	Domain

• Sequence:

  MEPVETWTPGKVATWLRGLDDSLQDYPFEDWQLPGKNLLQLCPQSLEALAVRSLGHQELI
  LGGVEQLQALSSRLQTENLQSLTEGLLGATHDFQSIVQGCLGDCAKTPIDVLCAAVELLH
  EADALLFWLSRYLFSHLNDFSACQEIRDLLEELSQVLHEDGPAAEKEGTVLRICSHVAGI
  CHNILVCCPKELLEQKAVLEQVQLDSPLGLEIHTTSNCQHFVSQVDTQVPTDSRLQIQPG
  DEVVQINEQVVVREERDMVGWPRKNMVRELLREPAGLSLVLKKIPIPETPPQTPPQVLDS
  PHQRSPSLSLAPLSPRAPSEDVFAFDLSSNPSPGPSPAWTDSASLGPEPLPIPPEPPAIL
  PAGVAGTPGLPESPDKSPVGRKKSKGLATRLSRRRVSCRELGRPDCDGWLLLRKAPGGFM
  GPRWRRRWFVLKGHTLYWYRQPQDEKAEGLINVSNYSLESGHDQKKKYVFQLTHDVYKPF
  IFAADTLTDLSMWVRHLITCISKYQSPGRAPPPREEDCYSETEAEDPDDEAGSHSASPSP
  AQAGSPLHGDTSPAATPTQRSPRTSFGSLTDSSEEALEGMVRGLRQGGVSLLGQPQPLTQ
  EQWRSSFMRRNRDPQLNERVHRVRALQSTLKAKLQELQVLEEVLGDPELTGEKFRQWKEQ
  NRELYSEGLGAWGVAQAEGSSHILTSDSTEQSPHSLPSDPEEHSHLCPLTSESSLRPPDL
  

• Sequence length: 720

Pathways

Reactome:

MAP2K and MAPK activation
Signaling by moderate kinase activity BRAF mutants
Signaling by high-kinase activity BRAF mutants
Signaling by BRAF and RAF fusions
Paradoxical activation of RAF signaling by kinase inactive BRAF
Signaling downstream of RAS mutants

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CNKSR1-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DISABILITY	—	CTD, Disgenet, GenCC CTD, Disgenet, GenCC CTD, Disgenet, GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL RETARDATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neurodevelopmental disorder	Uncertain significance	ClinVar CTD	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Usher syndrome type 2C	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Breast Carcinoma	Breast Carcinoma	BEFREE	20197385, 20383191		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	20197385	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	36790955	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	8603636		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	30450701		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	CTD_human_DG	21937992		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual Disability	Mental retardation	BEFREE	30450701		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung Neoplasms	Lung neoplasms	Pubtator	31040156	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	20197385, 20383191		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	28732488		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	20197385, 31040156		★☆☆☆☆ Found in Text Mining only
Mental deficiency	Mental retardation	CTD_human_DG	21937992		★☆☆☆☆ Found in Text Mining only
Microphthalmos	Microphthalmos	BEFREE	29450879		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	15075335, 28732488, 31040156		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	28732488		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	28732488, 36790955	Associate	★☆☆☆☆ Found in Text Mining only
Profound Mental Retardation	Mental retardation	CTD_human_DG	21937992		★☆☆☆☆ Found in Text Mining only
Thyroiditis Autoimmune	Thyroiditis	Pubtator	37501789	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	34541834, 35127296	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	20197385	Associate	★☆☆☆☆ Found in Text Mining only