KLHL2

Summary

KLHL2 (kelch like family member 2, HGNC:6353) is a protein-coding gene on chromosome 4q32.3, encoding Kelch-like protein 2 (O95198). Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, WNK1, WNK3 and WNK4, leading most often to their proteasomal degradation.

Enables actin binding activity; identical protein binding activity; and ubiquitin-like ligase-substrate adaptor activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process and protein ubiquitination. Located in actin cytoskeleton.

Source: NCBI Gene 11275 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 56 total
• Druggable target: yes
• MANE Select transcript: NM_007246

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6353
Approved symbol	KLHL2
Name	kelch like family member 2
Location	4q32.3
Locus type	gene with protein product
Status	Approved
Aliases	MAV
Ensembl gene	ENSG00000109466
Ensembl biotype	protein_coding
OMIM	605774
Entrez	11275

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 16 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000226725, ENST00000421009, ENST00000506541, ENST00000506761, ENST00000506824, ENST00000509028, ENST00000509704, ENST00000511305, ENST00000514860, ENST00000538127, ENST00000853227, ENST00000853228, ENST00000853229, ENST00000853230, ENST00000853231, ENST00000853232, ENST00000853233, ENST00000949378, ENST00000949379

RefSeq mRNA: 5 — MANE Select: NM_007246 NM_001161521, NM_001161522, NM_001331023, NM_001331024, NM_007246

CCDS: CCDS34094, CCDS54815, CCDS54816, CCDS82974, CCDS82975

Canonical transcript exons

ENST00000226725 — 15 exons

Exon	Start	End
ENSE00001362806	165207561	165207902
ENSE00003458884	165310553	165310750
ENSE00003496545	165228807	165228913
ENSE00003502576	165314026	165314166
ENSE00003511761	165305608	165305725
ENSE00003512615	165238778	165238899
ENSE00003558207	165299507	165299656
ENSE00003584750	165322032	165323147
ENSE00003587691	165219934	165220059
ENSE00003599842	165313238	165313366
ENSE00003602302	165317826	165317969
ENSE00003631560	165297609	165297725
ENSE00003655160	165294359	165294468
ENSE00003668422	165311464	165311565
ENSE00003687573	165263197	165263359

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.1084 / max 550.3680, expressed in 1801 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50434	10.6356	1773
50435	3.6650	1187
50433	2.0471	699
50432	0.6794	216
50436	0.0814	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.65	gold quality
CA1 field of hippocampus	UBERON:0003881	98.41	gold quality
postcentral gyrus	UBERON:0002581	97.99	gold quality
cranial nerve II	UBERON:0000941	97.97	gold quality
lateral globus pallidus	UBERON:0002476	97.93	gold quality
parietal lobe	UBERON:0001872	97.87	gold quality
superior frontal gyrus	UBERON:0002661	97.73	gold quality
middle temporal gyrus	UBERON:0002771	97.67	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.66	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.50	gold quality
orbitofrontal cortex	UBERON:0004167	97.45	gold quality
globus pallidus	UBERON:0001875	97.40	gold quality
Ammon’s horn	UBERON:0001954	97.38	gold quality
medial globus pallidus	UBERON:0002477	97.22	gold quality
corpus callosum	UBERON:0002336	97.20	gold quality
entorhinal cortex	UBERON:0002728	97.19	gold quality
inferior vagus X ganglion	UBERON:0005363	97.07	gold quality
endothelial cell	CL:0000115	97.06	gold quality
parotid gland	UBERON:0001831	96.85	gold quality
nucleus accumbens	UBERON:0001882	96.60	gold quality
primary visual cortex	UBERON:0002436	96.51	gold quality
occipital lobe	UBERON:0002021	96.43	gold quality
putamen	UBERON:0001874	96.38	gold quality
medulla oblongata	UBERON:0001896	96.35	gold quality
subthalamic nucleus	UBERON:0001906	96.25	gold quality
caudate nucleus	UBERON:0001873	96.06	gold quality
temporal lobe	UBERON:0001871	96.02	gold quality
telencephalon	UBERON:0001893	95.89	gold quality
corpus epididymis	UBERON:0004359	95.87	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

157 targeting KLHL2, 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-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669

Literature-anchored findings (GeneRIF, showing 3)

• overexpression of Mayven may promote tumor growth through c-Jun and cyclin D1 (PMID:15735724)
• Results suggest a novel E3 ubiquitin ligase function of KLHL2, with NPCD as a substrate. (PMID:21549840)
• Co-expression of KLHL2 and Cullin3 decreases the abundance of WNK1, WNK3 and WNK4 within HEK293T cells. (PMID:23838290)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	klhl2	ENSDARG00000061786
mus_musculus	Klhl2	ENSMUSG00000031605
rattus_norvegicus	Klhl2	ENSRNOG00000029441

Paralogs (54): KLHL13 (ENSG00000003096), KLHL20 (ENSG00000076321), KEAP1 (ENSG00000079999), KLHL42 (ENSG00000087448), KLHL22 (ENSG00000099910), KLHL4 (ENSG00000102271), KLHL5 (ENSG00000109790), BACH2 (ENSG00000112182), KLHL18 (ENSG00000114648), KLHL24 (ENSG00000114796), IVNS1ABP (ENSG00000116679), KLHL12 (ENSG00000117153), KLHL29 (ENSG00000119771), KBTBD7 (ENSG00000120696), KLHL7 (ENSG00000122550), KLHL31 (ENSG00000124743), KLHDC7B (ENSG00000130487), KLHL36 (ENSG00000135686), KLHL8 (ENSG00000145332), KLHL3 (ENSG00000146021), KLHL35 (ENSG00000149243), KLHL1 (ENSG00000150361), BACH1 (ENSG00000156273), KLHL40 (ENSG00000157119), KLHL10 (ENSG00000161594), KLHL21 (ENSG00000162413), KLHDC8A (ENSG00000162873), KBTBD8 (ENSG00000163376), KBTBD6 (ENSG00000165572), KLHL26 (ENSG00000167487), KLHL30 (ENSG00000168427), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL15 (ENSG00000174010), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Kelch-like protein 2 — O95198 (reviewed: O95198)

Alternative names: Actin-binding protein Mayven

All UniProt accessions (6): O95198, B4DFZ5, D6R9G5, D6RAP5, D6RGC3, E9PEX9

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, WNK1, WNK3 and WNK4, leading most often to their proteasomal degradation. The BCR(KLHL2) complex catalyzes ubiquitination and degradation of NPTXR. Responsible for degradative ubiquitination of the WNK kinases WNK1, WNK3 and WNK4. Plays a role in the reorganization of the actin cytoskeleton. Promotes growth of cell projections in oligodendrocyte precursors.

Subunit / interactions. Component of the BCR(KLHL2) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL2 and RBX1. Binds actin. Interacts with KLHL12. Interacts (via N-terminus) with FYN (via SH3 domain).

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Ruffle. Lamellipodium. Cytosol.

Tissue specificity. Ubiquitous. Detected throughout the brain.

Pathway. Protein modification; protein ubiquitination.

Isoforms (3)

UniProt ID	Names	Canonical?
O95198-1	1	yes
O95198-2	2
O95198-3	3

RefSeq proteins (5): NP_001154993, NP_001154994, NP_001317952, NP_001317953, NP_009177* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR006652	Kelch_1	Repeat
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR011705	BACK	Domain
IPR015915	Kelch-typ_b-propeller	Homologous_superfamily
IPR017096	BTB-kelch_protein	Family
IPR044072	KLHL2_BTB/POZ	Domain

Pfam: PF00651, PF01344, PF07707

UniProt features (54 total): strand 30, turn 7, repeat 6, sequence conflict 5, splice variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4CHB	X-RAY DIFFRACTION	1.56
2XN4	X-RAY DIFFRACTION	1.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95198-F1	92.31	0.85

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-8951664	Neddylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 204 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GGTGTGT_MIR329, chr4q32, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_RUFFLE, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, RHEIN_ALL_GLUCOCORTICOID_THERAPY_UP, NF1_Q6_01, GROSS_HYPOXIA_VIA_HIF1A_DN, TGTGTGA_MIR377

GO Biological Process (2): protein ubiquitination (GO:0016567), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (4): actin binding (GO:0003779), identical protein binding (GO:0042802), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (9): ruffle (GO:0001726), cytoplasm (GO:0005737), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), Cul3-RING ubiquitin ligase complex (GO:0031463), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Metabolism of proteins	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell leading edge	2
plasma membrane bounded cell projection	2
protein modification by small protein conjugation	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
cytoskeletal protein binding	1
protein binding	1
enzyme-substrate adaptor activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
cytoskeleton	1
cullin-RING ubiquitin ligase complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1012 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHL2	CUL3	Q13618	918
KLHL2	WNK4	Q96J92	702
KLHL2	WNK1	P54963	595
KLHL2	WNK3	Q9BYP7	537
KLHL2	SLC12A3	P55017	465
KLHL2	CPPED1	Q9BRF8	443
KLHL2	PCNP	Q8WW12	441
KLHL2	TULP4	Q9NRJ4	440
KLHL2	CTSO	P43234	431
KLHL2	GRIK1	P39086	430
KLHL2	SYT10	Q6XYQ8	420
KLHL2	KLHL3	Q9UH77	418
KLHL2	RNPEP	Q9H4A4	416
KLHL2	WDFY3	Q8IZQ1	404
KLHL2	UBE3A	P78355	400

IntAct

153 interactions, top by confidence:

A	B	Type	Score
KLHL2	CUL3	psi-mi:“MI:0915”(physical association)	0.880
CUL3	KLHL2	psi-mi:“MI:0915”(physical association)	0.880
KLHL2	KLHL12	psi-mi:“MI:0915”(physical association)	0.850
KLHL12	KLHL2	psi-mi:“MI:0914”(association)	0.850
KLHL12	KLHL2	psi-mi:“MI:0915”(physical association)	0.850
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
KLHL2	ZNF114	psi-mi:“MI:0915”(physical association)	0.780
TMA16	KLHL2	psi-mi:“MI:0915”(physical association)	0.780
KLHL2	TMA16	psi-mi:“MI:0915”(physical association)	0.780
ZNF114	KLHL2	psi-mi:“MI:0915”(physical association)	0.780
KLHL2	KEAP1	psi-mi:“MI:0915”(physical association)	0.770
KLHL2	KLHL2	psi-mi:“MI:0915”(physical association)	0.740
FBXL17	BACH1	psi-mi:“MI:0914”(association)	0.730
KLHL2	CLK2	psi-mi:“MI:0915”(physical association)	0.720
KLHL2	BCAM	psi-mi:“MI:0915”(physical association)	0.720
CLK2	KLHL2	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (188): KLHL2 (Two-hybrid), KLHL2 (Two-hybrid), KLHL2 (Two-hybrid), KLHL2 (Two-hybrid), KLHL2 (Two-hybrid), KLHL2 (Two-hybrid), TNPO2 (Two-hybrid), TXNDC12 (Two-hybrid), TMA16 (Two-hybrid), CCDC43 (Two-hybrid), ZNF114 (Two-hybrid), KLHL2 (Affinity Capture-RNA), KLHL2 (Affinity Capture-MS), KLHL2 (Affinity Capture-MS), KLHL12 (Two-hybrid)

ESM2 similar proteins: A0JMG1, A2VE52, D3K5L7, E0CZ16, E1C6Q1, E2R222, F1LZ52, F1LZF0, F1MBP6, O13016, O35345, O43791, O60684, O95164, O95198, O95544, P35815, P36993, P54797, P58058, P63143, P63144, Q0IHH9, Q0V7M0, Q0VCW1, Q15645, Q28528, Q28F89, Q2M2N2, Q2TA46, Q3UA06, Q4PJK1, Q5BL35, Q5NVK7, Q5RBV0, Q5REP9, Q5U1X1, Q5XHZ9, Q6GR09, Q6IQ16

Diamond homologs: A0A0A6YY25, B2RXH4, E0CZ16, E1B932, E7F6F9, F1LZ52, F1LZF0, F1MBP6, O88282, O93567, O95198, P10074, P17789, P42282, P42283, P42284, Q01295, Q1H9T6, Q24174, Q24206, Q3B7M1, Q52KG4, Q53G59, Q53HC5, Q5R633, Q5REP9, Q5U374, Q66HD2, Q6NRH0, Q7KQZ4, Q7KRI2, Q867Z4, Q86B87, Q8BGY4, Q8BZM0, Q8CA72, Q8IN81, Q8JZP3, Q8K0L9, Q8N143

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
KLHL2	“down-regulates quantity by destabilization”	WNK4	binding
KLHL2	“down-regulates quantity by destabilization”	WNK1	binding
KLHL2	“down-regulates quantity by destabilization”	WNK2	binding
KLHL2	“down-regulates quantity by destabilization”	WNK3	binding
KLHL2	“up-regulates activity”	“Cullin 3-RBX1-Skp1”	binding
KLHL2	“down-regulates quantity by destabilization”	UCK1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
ubiquitin-dependent protein catabolic process	6	10.4×	2e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	8	9.7×	4e-04
protein ubiquitination	8	7.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3588 predictions. Top by Δscore:

Variant	Effect	Δscore
4:165207901:GC:G	donor_gain	1.0000
4:165207903:G:GG	donor_gain	1.0000
4:165219926:A:AG	acceptor_gain	1.0000
4:165219927:T:G	acceptor_gain	1.0000
4:165219927:T:TA	acceptor_gain	1.0000
4:165219931:C:G	acceptor_gain	1.0000
4:165219932:A:AG	acceptor_gain	1.0000
4:165219932:AGAT:A	acceptor_gain	1.0000
4:165219933:G:GT	acceptor_gain	1.0000
4:165219933:GA:G	acceptor_gain	1.0000
4:165219933:GAT:G	acceptor_gain	1.0000
4:165219933:GATG:G	acceptor_gain	1.0000
4:165219933:GATGC:G	acceptor_gain	1.0000
4:165220056:GAAG:G	donor_gain	1.0000
4:165220057:A:T	donor_gain	1.0000
4:165228793:T:TA	acceptor_gain	1.0000
4:165228801:A:AG	acceptor_gain	1.0000
4:165228802:C:G	acceptor_gain	1.0000
4:165228802:CACA:C	acceptor_loss	1.0000
4:165228803:A:AG	acceptor_gain	1.0000
4:165228804:C:G	acceptor_gain	1.0000
4:165228805:A:AG	acceptor_gain	1.0000
4:165228805:A:G	acceptor_loss	1.0000
4:165228806:G:GG	acceptor_gain	1.0000
4:165228806:GT:G	acceptor_gain	1.0000
4:165228806:GTC:G	acceptor_gain	1.0000
4:165228806:GTCA:G	acceptor_gain	1.0000
4:165228806:GTCAA:G	acceptor_gain	1.0000
4:165228909:TACAG:T	donor_loss	1.0000
4:165228910:ACAGG:A	donor_loss	1.0000

AlphaMissense

3897 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:165228886:A:C	S78R	1.000
4:165228888:T:A	S78R	1.000
4:165228888:T:G	S78R	1.000
4:165228908:T:C	F85S	1.000
4:165263257:T:C	F148L	1.000
4:165263259:T:A	F148L	1.000
4:165263259:T:G	F148L	1.000
4:165263308:G:C	A165P	1.000
4:165263309:C:A	A165D	1.000
4:165297630:T:A	W226R	1.000
4:165297630:T:C	W226R	1.000
4:165297655:G:T	R234M	1.000
4:165299567:G:C	A278P	1.000
4:165299634:G:C	R300T	1.000
4:165299634:G:T	R300M	1.000
4:165299635:G:C	R300S	1.000
4:165299635:G:T	R300S	1.000
4:165305623:G:A	G313R	1.000
4:165305623:G:C	G313R	1.000
4:165305623:G:T	G313W	1.000
4:165305624:G:A	G313E	1.000
4:165305624:G:T	G313V	1.000
4:165305626:G:C	G314R	1.000
4:165305627:G:A	G314D	1.000
4:165305627:G:T	G314V	1.000
4:165305642:C:A	A319D	1.000
4:165305683:T:A	W333R	1.000
4:165305683:T:C	W333R	1.000
4:165305685:G:C	W333C	1.000
4:165305685:G:T	W333C	1.000

dbSNP variants (sampled 300 via entrez): RS1000007012 (4:165240544 T>G), RS10000653 (4:165243103 C>G), RS1000076864 (4:165247110 G>A,C), RS1000113036 (4:165265830 A>G), RS1000156652 (4:165213640 A>G), RS1000168231 (4:165260561 CAT>C,CATAT), RS1000203311 (4:165315206 G>A), RS1000249155 (4:165265647 A>G), RS1000285608 (4:165293743 C>T), RS1000327771 (4:165226314 G>A,C,T), RS1000423691 (4:165216973 G>A,T), RS1000427358 (4:165278873 C>T), RS1000454543 (4:165284762 T>C), RS1000481871 (4:165249899 T>C,G), RS10005213 (4:165232442 A>G)

Disease associations

OMIM: gene MIM:605774 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002386_12	Cognitive function	6.000000e-06
GCST003447_4	Neuroticism	4.000000e-08
GCST006269_1173	General cognitive ability	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003925	cognition
EFO:0007660	neuroticism measurement
EFO:0004337	intelligence

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196064 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
methylselenic acid	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Clorgyline	increases expression	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Ozone	increases abundance, affects expression	1
Quercetin	decreases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6094264	Binding	Binding affinity to KLHL2 (unknown origin) at 10 uM by thermal shift assay	Structure-Guided Conformational Restriction Leading to High-Affinity, Selective, and Cell-Active Tetrahydroisoquinoline-Based Noncovalent Keap1-Nrf2 Inhibitors. — J Med Chem

Clinical trials (associated diseases)

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