CNKSR1

Summary

CNKSR1 (connector enhancer of kinase suppressor of Ras 1, HGNC:19700) is a protein-coding gene on chromosome 1p36.11, encoding Connector enhancer of kinase suppressor of ras 1 (Q969H4). May function as an adapter protein or regulator of Ras signaling pathways.

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 signaling and may mediate crosstalk between different signaling pathways. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10256 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 130 total
• Druggable target: yes
• MANE Select transcript: NM_006314

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19700
Approved symbol	CNKSR1
Name	connector enhancer of kinase suppressor of Ras 1
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	CNK1, KSR, CNK
Ensembl gene	ENSG00000142675
Ensembl biotype	protein_coding
OMIM	603272
Entrez	10256

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 7 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000361530, ENST00000374253, ENST00000465415, ENST00000480348, ENST00000480617, ENST00000481077, ENST00000482227, ENST00000484874, ENST00000524529, ENST00000525687, ENST00000528001, ENST00000528281, ENST00000531150, ENST00000531191, ENST00000878392, ENST00000878393, ENST00000878394, ENST00000878395

RefSeq mRNA: 3 — MANE Select: NM_006314 NM_001297647, NM_001297648, NM_006314

CCDS: CCDS276, CCDS72732, CCDS76124

Canonical transcript exons

ENST00000361530 — 21 exons

Exon	Start	End
ENSE00001917680	26189279	26189884
ENSE00002189456	26177491	26177599
ENSE00003466672	26184214	26184287
ENSE00003472888	26184071	26184141
ENSE00003530096	26182480	26182584
ENSE00003533488	26180453	26180610
ENSE00003549066	26184585	26184612
ENSE00003555335	26187168	26187241
ENSE00003557528	26188598	26188697
ENSE00003557897	26184401	26184507
ENSE00003566562	26183729	26183830
ENSE00003568083	26181857	26181941
ENSE00003581065	26182361	26182402
ENSE00003585878	26188442	26188503
ENSE00003602215	26188234	26188307
ENSE00003628683	26183197	26183256
ENSE00003641966	26183346	26183414
ENSE00003649340	26188772	26188953
ENSE00003658481	26180715	26180896
ENSE00003669837	26187411	26187482
ENSE00003677721	26185014	26185186

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 96.66.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6907 / max 64.2795, expressed in 492 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1563	2.5868	482
1564	0.1039	19

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	96.66	gold quality
gastrocnemius	UBERON:0001388	95.97	gold quality
right lobe of thyroid gland	UBERON:0001119	94.63	gold quality
muscle of leg	UBERON:0001383	94.52	gold quality
lower esophagus mucosa	UBERON:0035834	94.21	gold quality
muscle organ	UBERON:0001630	93.32	gold quality
left lobe of thyroid gland	UBERON:0001120	93.00	gold quality
right uterine tube	UBERON:0001302	93.00	gold quality
body of pancreas	UBERON:0001150	92.61	gold quality
mucosa of transverse colon	UBERON:0004991	92.61	gold quality
minor salivary gland	UBERON:0001830	92.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.11	gold quality
thyroid gland	UBERON:0002046	92.09	gold quality
esophagus mucosa	UBERON:0002469	91.62	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.95	gold quality
mouth mucosa	UBERON:0003729	90.56	gold quality
vastus lateralis	UBERON:0001379	90.50	gold quality
skeletal muscle tissue	UBERON:0001134	90.45	gold quality
saliva-secreting gland	UBERON:0001044	90.31	gold quality
tongue squamous epithelium	UBERON:0006919	90.27	gold quality
quadriceps femoris	UBERON:0001377	90.10	gold quality
skin of abdomen	UBERON:0001416	89.98	gold quality
skin of leg	UBERON:0001511	89.14	gold quality
gluteal muscle	UBERON:0002000	88.99	gold quality
rectum	UBERON:0001052	88.84	gold quality
biceps brachii	UBERON:0001507	88.83	gold quality
triceps brachii	UBERON:0001509	88.52	gold quality
pancreatic ductal cell	CL:0002079	88.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.24	gold quality
transverse colon	UBERON:0001157	87.55	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

miRNA regulators (miRDB)

21 targeting CNKSR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-874-5P	96.93	63.92	1014

Literature-anchored findings (GeneRIF, showing 17)

• hCNK1 associates with Rhophilin and RalGDS, Rho and Ras effector molecules, respectively, suggesting that it acts as a scaffold protein to mediate cross talk between the two pathways (PMID:14749388)
• Data show that the connector enhancer of KSR 1 scaffold protein, through its binding of a RASSF1A/MST1 complex, participates in the proapoptotic signaling initiated by active Ras. (PMID:15075335)
• CNK1 couples a subset of Rho exchange factors to activation of the JNK MAP kinase pathway and that signaling specificity is achieved through complexes containing both upstream activators and downstream targets of Rho. (PMID:15753034)
• CNK1 allows cross-talk between Src and Raf-1 and is essential for the full activation of Raf-1 (PMID:15845549)
• CNK1 binds through the sterile alpha motif (SAM) and the conserved region in CNK (CRIC) to the AT2 receptor. CNK1 may play a role in the AT2 receptor-mediated signaling pathways. (PMID:16289034)
• DC-SIGN was constitutively associated with a signalosome complex consisting of the scaffold proteins LSP1, KSR1 and CNK and the kinase Raf-1. (PMID:19718030)
• Thus, CNK1 is an essential mediator of an oncogenic pathway involved in invasion of breast and cervical cancer cells and is therefore a putative target for cancer therapy. (PMID:20197385)
• CNK1 promotes oncogenic signalling through Akt in breast cancer cell lines and tumours. (PMID:20383191)
• These findings identify CNK1 as a new positive regulator of insulin signaling. (PMID:20634316)
• Studies indicate that CNK1-driven proliferation relies on Akt-dependent phosphorylation and inactivation of FoxO proteins. (PMID:21320536)
• CNK1 mediates ephrinB1 signaling that promotes cell migration through RhoA and JNK activity. (PMID:24825906)
• tyrosine phosphorylation is an important mechanism to control the subcellular localization of CNK1 and its distinct biological functions. (PMID:26319181)
• The findings reveal SAM domain-dependent oligomerization by AKT as a switch for CNK1 activation. (PMID:27769899)
• Data indicate connector enhancer of kinase suppressor of Ras 1 protein (CNK1) as a molecular platform that controls c-raf protein (RAF) and c-akt protein (AKT) signalling and determines cell fate decisions in a cell type- and cell stage-dependent manner. (PMID:27901111)
• CNKSR1 expression is increased in pancreatic cancer specimens and was found to be an independent prognostic marker of overall survival. (PMID:28732488)
• RNAi-mediated knockdown of cnk, the CNKSR1 orthologue in Drosophila melanogaster brain, led to defects in eye and mushroom body (MB) structures. Findings support the possible role of CNKSR1 in brain development which can lead to cognitive impairment. (PMID:30450701)
• CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP. (PMID:34187934)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnksr1	ENSDARG00000032932
mus_musculus	Cnksr1	ENSMUSG00000028841
rattus_norvegicus	Cnksr1	ENSRNOG00000022838
drosophila_melanogaster	cnk	FBGN0286070
caenorhabditis_elegans		WBGENE00000564

Paralogs (4): IPCEF1 (ENSG00000074706), CNKSR2 (ENSG00000149970), CNKSR3 (ENSG00000153721), SAMD3 (ENSG00000164483)

Protein

Protein identifiers

Connector enhancer of kinase suppressor of ras 1 — Q969H4 (reviewed: Q969H4)

Alternative names: CNK homolog protein 1, Connector enhancer of KSR-like

All UniProt accessions (7): Q969H4, B4DXN4, E9PIE0, E9PS82, G3V160, H0YDP5, Q53GM7

UniProt curated annotations — full annotation on UniProt →

Function. May function as an adapter protein or regulator of Ras signaling pathways.

Subunit / interactions. Interacts with RHO and RALGDS.

Subcellular location. Cytoplasm. Membrane.

Post-translational modifications. Phosphorylated on tyrosine.

Similarity. Belongs to the CNKSR family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q969H4-1	1	yes
Q969H4-2	2

RefSeq proteins (3): NP_001284576, NP_001284577, NP_006305* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR001660	SAM	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR017874	CRIC_domain	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR049628	CNK1-3_SAM	Domain
IPR051566	CNKSR	Family

Pfam: PF00169, PF10534

UniProt features (32 total): compositionally biased region 7, helix 6, domain 4, turn 4, region of interest 3, modified residue 2, chain 1, splice variant 1, sequence variant 1, mutagenesis site 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1WWV	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969H4-F1	69.06	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 307, 314

Mutagenesis-validated functional residues (1):

Position	Phenotype
493	no interaction with rho.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-5674135	MAP2K and MAPK activation
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-9649948	Signaling downstream of RAS mutants
R-HSA-9656223	Signaling by RAF1 mutants

MSigDB gene sets: 112 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, CREL_01, MORF_MSH3, MORF_BRCA1, MODULE_16, MODULE_118, MODULE_88, GFI1_01, RYTTCCTG_ETS2_B, MODULE_6, MARIADASON_REGULATED_BY_HISTONE_ACETYLATION_UP, GOCC_CELL_CELL_JUNCTION, MODULE_60, MORF_PPP2R5B

GO Biological Process (1): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169)

GO Molecular Function (3): protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (5): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), cell cortex (GO:0005938), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Oncogenic MAPK signaling	5
RAF/MAP kinase cascade	1
Signaling by RAS mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell periphery	2
cellular anatomical structure	2
enzyme-linked receptor protein signaling pathway	1
protein binding	1
molecular adaptor activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
membrane	1
anchoring junction	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNKSR1	KSR1	Q8IVT5	895
CNKSR1	RASSF1	Q9NS23	885
CNKSR1	RHPN1	Q8TCX5	789
CNKSR1	RALGDS	Q12967	777
CNKSR1	MAP3K10	Q02779	683
CNKSR1	EFNB1	P98172	653
CNKSR1	RASSF5	Q8WWW0	630
CNKSR1	MAP2K7	O14733	621
CNKSR1	ARHGEF1	Q92888	557
CNKSR1	PLEK2	Q9NYT0	556
CNKSR1	RHOA	P06749	545
CNKSR1	PLEK	P08567	527
CNKSR1	EFNB3	Q15768	482
CNKSR1	MAP3K11	Q16584	467
CNKSR1	SYDE2	Q5VT97	460

IntAct

88 interactions, top by confidence:

A	B	Type	Score
CNKSR1	CYTH3	psi-mi:“MI:0915”(physical association)	0.740
CYTH3	CNKSR1	psi-mi:“MI:0915”(physical association)	0.740
CYTH1	CNKSR1	psi-mi:“MI:0915”(physical association)	0.740
CNKSR1	PIN1	psi-mi:“MI:0915”(physical association)	0.720
PIN1	CNKSR1	psi-mi:“MI:0915”(physical association)	0.720
CNKSR1	CYTH4	psi-mi:“MI:0915”(physical association)	0.670
CYTH3	CNKSR1	psi-mi:“MI:0915”(physical association)	0.670
CNKSR1	CYTH2	psi-mi:“MI:0915”(physical association)	0.670
CNKSR1	CYTH4	psi-mi:“MI:0915”(physical association)	0.560
CNKSR1	TCAF1	psi-mi:“MI:0915”(physical association)	0.560
ZGPAT	CNKSR1	psi-mi:“MI:0915”(physical association)	0.560
SMAD4	CNKSR1	psi-mi:“MI:2364”(proximity)	0.520
CNKSR1	SMAD4	psi-mi:“MI:0915”(physical association)	0.520
RHOA	CNKSR1	psi-mi:“MI:2364”(proximity)	0.470
RHOA	CNKSR1	psi-mi:“MI:0915”(physical association)	0.470
CNKSR1	RHOA	psi-mi:“MI:0915”(physical association)	0.470
CNKSR1	BRAF	psi-mi:“MI:2364”(proximity)	0.470
CNKSR1	BRAF	psi-mi:“MI:0915”(physical association)	0.470
E6	CNKSR1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (68): CNKSR1 (Two-hybrid), CNKSR1 (Two-hybrid), CYTH4 (Two-hybrid), CNKSR1 (Two-hybrid), CNKSR1 (Two-hybrid), CNKSR1 (Two-hybrid), RHOA (Reconstituted Complex), CNKSR1 (Affinity Capture-Western), RHPN1 (Affinity Capture-Western), RHPN1 (Reconstituted Complex), CNKSR1 (Affinity Capture-Western), CNKSR1 (Affinity Capture-Western), CYTH2 (Affinity Capture-MS), CYTH1 (Affinity Capture-MS), CYTH3 (Affinity Capture-MS)

ESM2 similar proteins: A1IGU3, A1IGU4, A1IGU5, A6QP29, A7E3N7, B1AVH7, B2RUP2, B5DFA1, D2H0G5, D3ZFJ3, O15068, O55043, O94812, P00530, P07332, P14238, P16879, P55194, P97680, P98171, Q27J81, Q3U5C8, Q58EX7, Q5VV41, Q60I26, Q60I27, Q63406, Q64096, Q6PFY1, Q6PGG2, Q70J99, Q80TT2, Q80UW5, Q80VK6, Q86WN1, Q8C2K1, Q8C6B2, Q8CJ00, Q8IW93, Q8R5I4

Diamond homologs: A0A0G2JUG7, A2A5R2, A5PKW4, A6H7I5, B6RSP1, D3ZL52, D4A631, E1JIT7, F1MUS9, F4IXW2, F4JN05, F4JSZ5, F4K2K3, G3X9K3, G5EET6, G5EGS5, O08967, O13817, O43739, O46382, P08567, P11075, P31749, P31751, P34512, P39052, P39054, P39993, P47102, P47196, P50570, P54644, P60669, P63034, P63035, P97694, P97696, Q00IB7, Q01314, Q10491

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CNKSR1	up-regulates	RAF1	binding
CNKSR1	up-regulates	RASSF1	binding
SRC	“up-regulates activity”	CNKSR1	phosphorylation
CNKSR1	“up-regulates activity”	EPHB1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

130 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	11
Benign	14

Top pathogenic / likely-pathogenic (0)

SpliceAI

3172 predictions. Top by Δscore:

Variant	Effect	Δscore
1:26180450:CA:C	acceptor_loss	1.0000
1:26180451:A:AG	acceptor_gain	1.0000
1:26180451:A:AT	acceptor_loss	1.0000
1:26180452:G:GG	acceptor_gain	1.0000
1:26180607:CCTGG:C	donor_loss	1.0000
1:26180610:GGT:G	donor_loss	1.0000
1:26180611:G:A	donor_loss	1.0000
1:26180611:G:GG	donor_gain	1.0000
1:26180612:T:A	donor_loss	1.0000
1:26180712:C:G	acceptor_gain	1.0000
1:26180713:A:AG	acceptor_gain	1.0000
1:26180714:G:GG	acceptor_gain	1.0000
1:26180714:GA:G	acceptor_gain	1.0000
1:26180893:GCAG:G	donor_gain	1.0000
1:26181852:GCCA:G	acceptor_loss	1.0000
1:26181853:CCA:C	acceptor_loss	1.0000
1:26181854:CAG:C	acceptor_loss	1.0000
1:26181855:A:AC	acceptor_loss	1.0000
1:26181856:G:GA	acceptor_loss	1.0000
1:26182474:CCCCA:C	acceptor_loss	1.0000
1:26182475:CCCAG:C	acceptor_loss	1.0000
1:26182476:CCA:C	acceptor_loss	1.0000
1:26182477:CAG:C	acceptor_loss	1.0000
1:26182478:A:AG	acceptor_gain	1.0000
1:26182478:A:C	acceptor_loss	1.0000
1:26182479:G:GT	acceptor_gain	1.0000
1:26182479:GT:G	acceptor_gain	1.0000
1:26182479:GTGC:G	acceptor_gain	1.0000
1:26182479:GTGCA:G	acceptor_gain	1.0000
1:26182585:G:GG	donor_gain	1.0000

AlphaMissense

4589 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:26187416:T:C	F470S	0.992
1:26187452:T:C	F482S	0.989
1:26188235:T:A	W493R	0.989
1:26188235:T:C	W493R	0.989
1:26185127:T:A	W424R	0.988
1:26185127:T:C	W424R	0.988
1:26187415:T:C	F470L	0.987
1:26187417:T:A	F470L	0.987
1:26187417:T:G	F470L	0.987
1:26188237:G:C	W493C	0.987
1:26188237:G:T	W493C	0.987
1:26185172:T:G	Y439D	0.985
1:26185173:A:C	Y439S	0.985
1:26187422:T:C	L472P	0.985
1:26185129:G:C	W424C	0.984
1:26185129:G:T	W424C	0.984
1:26187455:C:A	A483D	0.983
1:26177590:T:A	W15R	0.979
1:26177590:T:C	W15R	0.979
1:26187422:T:A	L472H	0.979
1:26188450:A:C	S520R	0.978
1:26188452:T:A	S520R	0.978
1:26188452:T:G	S520R	0.978
1:26177566:T:A	W7R	0.977
1:26177566:T:C	W7R	0.977
1:26185166:T:G	Y437D	0.977
1:26185172:T:C	Y439H	0.977
1:26187451:T:C	F482L	0.976
1:26187453:C:A	F482L	0.976
1:26187453:C:G	F482L	0.976

dbSNP variants (sampled 300 via entrez): RS1000138432 (1:26181425 G>A), RS1000314466 (1:26175769 T>C), RS1000344212 (1:26175931 G>A), RS1000583714 (1:26181705 C>T), RS1000651496 (1:26176786 C>T), RS1001002178 (1:26185410 G>A,T), RS1001130073 (1:26179288 A>C), RS1001660477 (1:26189963 C>A), RS1002131005 (1:26177773 C>G), RS1002287451 (1:26185939 A>C), RS1002506511 (1:26182867 G>A,T), RS1003059795 (1:26182694 CTTTT>C), RS1003251007 (1:26189108 C>T), RS1003262667 (1:26184624 G>A,C), RS1003490504 (1:26178310 G>A)

Disease associations

OMIM: gene MIM:603272 | disease phenotypes: MIM:605472

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability	Limited	Autosomal recessive
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (3): neurodevelopmental disorder (MONDO:0700092), Usher syndrome type 2C (MONDO:0011558), intellectual disability (MONDO:0001071)

Orphanet (2): Usher syndrome type 2 (Orphanet:231178), Usher syndrome (Orphanet:886)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008476_23	Emphysema annual change measurement in smokers (percent low attenuation area)	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007626	emphysema imaging measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C536492	Usher syndrome, type 2C (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296242 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

22 potent at pChembl≥5 of 36 total, top 20 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.71	Kd	0.196	nM	CHEMBL4540854
7.58	Kd	26	nM	CHEMBL4528582
6.80	Kd	157	nM	CHEMBL4451466
6.73	Kd	186	nM	CHEMBL4293794
6.57	Kd	270	nM	CHEMBL4576938
6.52	Kd	300	nM	CHEMBL4578514
6.52	Kd	300	nM	CHEMBL4441711
6.21	Kd	614	nM	CHEMBL4451129
6.19	Kd	650	nM	CHEMBL4464276
6.16	Kd	700	nM	CHEMBL4527350
6.16	Kd	700	nM	CHEMBL4473657
5.81	Kd	1560	nM	CHEMBL4439996
5.75	Kd	1800	nM	CHEMBL1422005
5.54	Kd	2860	nM	CHEMBL4437164
5.48	Kd	3300	nM	CHEMBL4588492
5.47	Kd	3370	nM	CHEMBL4283567
5.38	Kd	4120	nM	CHEMBL4542845
5.38	Kd	4200	nM	CHEMBL4533907
5.28	Kd	5200	nM	CHEMBL4460680
5.10	Kd	7900	nM	CHEMBL4288751

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	increases phosphorylation	1
Calcitriol	increases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Copper	affects cotreatment, decreases expression	1
Estradiol	decreases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases expression	1
Asbestos, Crocidolite	affects expression	1
Cadmium Chloride	decreases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4419254	Binding	Binding affinity to CNKSR1 PH-domain (unknown origin) by SPR spectroscopy	Methods and compositions for inhibiting cnksr1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SJ35	HAP1 CNKSR1 (-) 1	Cancer cell line	Male
CVCL_SJ36	HAP1 CNKSR1 (-) 2	Cancer cell line	Male
CVCL_SJ37	HAP1 CNKSR1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

390 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study