KLHL21

Summary

KLHL21 (kelch like family member 21, HGNC:29041) is a protein-coding gene on chromosome 1p36.31, encoding Kelch-like protein 21 (Q9UJP4). Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis.

Enables cullin family protein binding activity. Contributes to ubiquitin-protein transferase activity. Involved in chromosome passenger complex localization to spindle midzone; protein ubiquitination; and regulation of cytokinesis. Located in polar microtubule. Part of Cul3-RING ubiquitin ligase complex.

Source: NCBI Gene 9903 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 120 total
• Druggable target: yes
• MANE Select transcript: NM_014851

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29041
Approved symbol	KLHL21
Name	kelch like family member 21
Location	1p36.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0469
Ensembl gene	ENSG00000162413
Ensembl biotype	protein_coding
OMIM	616262
Entrez	9903

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000377658, ENST00000377663, ENST00000463043, ENST00000467612, ENST00000496707

RefSeq mRNA: 2 — MANE Select: NM_014851 NM_001324309, NM_014851

CCDS: CCDS30575

Canonical transcript exons

ENST00000377658 — 4 exons

Exon	Start	End
ENSE00001474763	6590724	6593658
ENSE00001474768	6601797	6602869
ENSE00002950579	6595485	6595557
ENSE00003681878	6599047	6599452

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 97.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.9225 / max 445.3931, expressed in 1795 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10059	14.1927	1785
10060	0.9996	610
10061	0.5554	131
10057	0.1748	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	97.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.52	gold quality
gluteal muscle	UBERON:0002000	96.33	gold quality
muscle of leg	UBERON:0001383	96.22	gold quality
amniotic fluid	UBERON:0000173	95.81	gold quality
muscle organ	UBERON:0001630	95.01	gold quality
cervix squamous epithelium	UBERON:0006922	94.73	silver quality
cartilage tissue	UBERON:0002418	94.52	gold quality
right coronary artery	UBERON:0001625	94.07	gold quality
tibialis anterior	UBERON:0001385	93.99	gold quality
apex of heart	UBERON:0002098	93.70	gold quality
popliteal artery	UBERON:0002250	93.56	gold quality
tibial artery	UBERON:0007610	93.53	gold quality
descending thoracic aorta	UBERON:0002345	93.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.41	gold quality
lower esophagus	UBERON:0013473	93.40	gold quality
aorta	UBERON:0000947	93.33	gold quality
right atrium auricular region	UBERON:0006631	93.13	gold quality
thoracic aorta	UBERON:0001515	93.10	gold quality
ascending aorta	UBERON:0001496	93.02	gold quality
body of tongue	UBERON:0011876	92.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.93	gold quality
left coronary artery	UBERON:0001626	92.46	gold quality
heart left ventricle	UBERON:0002084	92.43	gold quality
coronary artery	UBERON:0001621	92.37	gold quality
quadriceps femoris	UBERON:0001377	92.36	gold quality
cardiac atrium	UBERON:0002081	92.32	gold quality
triceps brachii	UBERON:0001509	92.30	gold quality
mucosa of stomach	UBERON:0001199	92.23	gold quality
cardiac ventricle	UBERON:0002082	92.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

54 targeting KLHL21, 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-6798-5P	100.00	65.77	699
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-877-3P	99.09	68.10	1637

Literature-anchored findings (GeneRIF, showing 4)

• KLHL21 localizes to midzone microtubules in anaphase & recruits aurora B & Cul3 to this region; results suggest that different Cul3 adaptors nonredundantly regulate aurora B during mitosis, possibly by ubiquitinating different pools of aurora B (PMID:19995937)
• data clearly demonstrate that KLHL21 negatively regulates TNFalpha-activated NF-kappaB signaling via targeting IKKbeta, providing new insight into the mechanisms underlying NF-kappaB regulation in cells. (PMID:27387502)
• Our study suggests that KLHL21 is a potential target for therapeutic intervention. Our findings also provide novel candidate genes on a genome-wide scale, which may have significant impact on the design and execution of effective therapy of HCC patients. (PMID:27769251)
• KLHL21 plays an essential role in the tumorigenesis and progression of cholangiocarcinoma. (PMID:29574153)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	klhl21	ENSDARG00000039255
mus_musculus	Klhl21	ENSMUSG00000073700
rattus_norvegicus	Klhl21	ENSRNOG00000003334

Paralogs (54): KLHL13 (ENSG00000003096), KLHL20 (ENSG00000076321), KEAP1 (ENSG00000079999), KLHL42 (ENSG00000087448), KLHL22 (ENSG00000099910), KLHL4 (ENSG00000102271), KLHL2 (ENSG00000109466), 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), 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 21 — Q9UJP4 (reviewed: Q9UJP4)

All UniProt accessions (4): Q9UJP4, K7ELI0, K7EMF2, K7ESH2

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. Ubiquitination of AURKB by BCR(KLHL21) E3 ubiquitin ligase complex may not lead to its degradation by the proteasome.

Subunit / interactions. Component of the BCR(KLHL21) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL21 and RBX1.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UJP4-1	1	yes
Q9UJP4-2	2

RefSeq proteins (2): NP_001311238, NP_055666* (*=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
IPR030577	BTB/POZ_KLHL21	Domain
IPR047069	KLHL21_BACK	Domain

Pfam: PF00651, PF01344, PF07707

UniProt features (17 total): repeat 6, sequence conflict 3, domain 2, splice variant 2, chain 1, compositionally biased region 1, mutagenesis site 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJP4-F1	90.58	0.85

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
114–117	abolishes interaction with cul3.

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: 209 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, PEREZ_TP63_TARGETS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, WHITE_NEUROBLASTOMA_WITH_1P36.3_DELETION, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOCC_MICROTUBULE_ORGANIZING_CENTER, SETLUR_PROSTATE_CANCER_TMPRSS2_ERG_FUSION_DN, GOBP_CYTOKINESIS, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, GOBP_REGULATION_OF_CYTOKINESIS, GOBP_REGULATION_OF_CELL_DIVISION

GO Biological Process (5): protein ubiquitination (GO:0016567), regulation of cytokinesis (GO:0032465), chromosome passenger complex localization to spindle midzone (GO:0035853), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), cell division (GO:0051301)

GO Molecular Function (4): cullin family protein binding (GO:0097602), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), polar microtubule (GO:0005827), cytosol (GO:0005829), Cul3-RING ubiquitin ligase complex (GO:0031463), spindle (GO:0005819), cytoskeleton (GO:0005856)

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	2
intracellular membraneless organelle	2
protein modification by small protein conjugation	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
protein-containing complex localization	1
protein localization to cytoskeleton	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
cellular process	1
protein binding	1
enzyme-substrate adaptor activity	1
ubiquitin-like protein transferase activity	1
binding	1
intracellular anatomical structure	1
spindle pole	1
spindle microtubule	1
cytoplasm	1
cullin-RING ubiquitin ligase complex	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLHL21	CUL3	Q13618	729
KLHL21	ANKRD9	Q96BM1	560
KLHL21	ASB14	A6NK59	541
KLHL21	ASB11	Q8WXH4	536
KLHL21	NOL9	Q5SY16	532
KLHL21	PLK1	P53350	516
KLHL21	B7Z1P2	B7Z1P2	508
KLHL21	FBXL17	Q9UF56	508
KLHL21	IKBKB	O14920	490
KLHL21	ZNRF1	Q8ND25	445
KLHL21	SEC14L1	Q92503	442
KLHL21	FBXO32	Q969P5	440
KLHL21	TRIM63	Q969Q1	431
KLHL21	THAP3	Q8WTV1	424
KLHL21	FBXL22	Q6P050	422

IntAct

64 interactions, top by confidence:

A	B	Type	Score
KLHL12	KLHL2	psi-mi:“MI:0914”(association)	0.850
FBXL17	SKP1	psi-mi:“MI:0914”(association)	0.790
HOXA9	TRIP6	psi-mi:“MI:0914”(association)	0.750
KLHL24	CUL3	psi-mi:“MI:0914”(association)	0.730
FBXL17	BACH1	psi-mi:“MI:0914”(association)	0.730
RCL1	BMS1	psi-mi:“MI:0914”(association)	0.690
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
KLHL21	CUL3	psi-mi:“MI:0914”(association)	0.640
CUL3	ENC1	psi-mi:“MI:0914”(association)	0.640
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
HOXC9	AHCYL1	psi-mi:“MI:0914”(association)	0.640
KLHL9	ENC1	psi-mi:“MI:0914”(association)	0.640
KLC3	KLHL21	psi-mi:“MI:0915”(physical association)	0.560
CUL3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
YJU2B	RCCD1	psi-mi:“MI:0914”(association)	0.530
KLHL9	KLHL26	psi-mi:“MI:0914”(association)	0.530
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	KLHL18	psi-mi:“MI:0914”(association)	0.350
CUL3	KLHL2	psi-mi:“MI:0914”(association)	0.350
RPL28	SDCBP	psi-mi:“MI:0914”(association)	0.350
ZNF263	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
TPM1	SPAG9	psi-mi:“MI:0914”(association)	0.350
KLHL28	PRKACB	psi-mi:“MI:0914”(association)	0.350
TNNI2	NUCB2	psi-mi:“MI:0914”(association)	0.350
ZBTB44	NAE1	psi-mi:“MI:0914”(association)	0.350
KLHL29	NPHP3	psi-mi:“MI:0914”(association)	0.350
KLHL12	SKP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): KLHL21 (Affinity Capture-MS), KLHL21 (Affinity Capture-MS), KLHL21 (Affinity Capture-MS), KLHL21 (Affinity Capture-MS), CUL3 (Affinity Capture-Western), IKBKB (Affinity Capture-Western), IKBKB (Reconstituted Complex), KLHL21 (Affinity Capture-Western), KLHL21 (Affinity Capture-Western), KLHL21 (Affinity Capture-Western), MAPRE1 (Reconstituted Complex), KLHL21 (Affinity Capture-Western), MAPRE1 (Biochemical Activity), KLHL21 (Affinity Capture-MS), KLHL21 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A4FV98, A6QPA3, C9J798, C9JJ37, D3YWP0, D3ZVU9, D4A2K4, O43374, O70277, O75382, O95294, P0C6S8, P22674, P57775, Q08DS0, Q0GA42, Q3U410, Q3UGX3, Q4G0W2, Q4V892, Q5SUV1, Q5XIU1, Q6GQU6, Q6IA17, Q6PF15, Q6TDP3, Q6TDP4, Q7TNM2, Q7Z4K8, Q86WI3, Q8CIW5, Q8IZ69, Q8K430, Q8N531, Q8N8L6, Q8NE01, Q8WXI3, Q969K4

Diamond homologs: A0JMG1, A1YEX3, B0WWP2, B3DIV9, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, B7U179, D3Z8N4, D4A2K4, E0CZ16, E7F6F9, F1LZF0, F1MBP6, O14682, O22286, O35709, O43791, O81432, O95198, P0DMR5, P0DMR6, P24278, P28575, P34568, P58544, P58545, Q08DK3, Q08DS0, Q0D2A9, Q0IHH9, Q0VCW1, Q16RL8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
KLHL21	“up-regulates activity”	AURKB	binding
KLHL21	“up-regulates activity”	EB1/MLL	binding
KLHL21	“up-regulates activity”	“Cullin 3-RBX1-Skp1”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neddylation	8	7.7×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	9	6.4×	2e-03
protein ubiquitination	10	5.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

439 predictions. Top by Δscore:

Variant	Effect	Δscore
1:6595480:TTTA:T	donor_loss	1.0000
1:6595481:TTACC:T	donor_loss	1.0000
1:6595482:TA:T	donor_loss	1.0000
1:6595483:A:AG	donor_loss	1.0000
1:6595484:C:CG	donor_loss	1.0000
1:6595553:CATCC:C	acceptor_gain	1.0000
1:6595555:TCC:T	acceptor_gain	1.0000
1:6595556:CC:C	acceptor_gain	1.0000
1:6595556:CCC:C	acceptor_gain	1.0000
1:6595557:CC:C	acceptor_gain	1.0000
1:6595558:C:A	acceptor_loss	1.0000
1:6595558:C:CC	acceptor_gain	1.0000
1:6595559:T:A	acceptor_loss	1.0000
1:6599042:CTCA:C	donor_loss	1.0000
1:6599044:CAC:C	donor_loss	1.0000
1:6599045:A:AC	donor_gain	1.0000
1:6599045:ACCT:A	donor_loss	1.0000
1:6599046:C:CC	donor_gain	1.0000
1:6599046:CCTGA:C	donor_gain	1.0000
1:6599450:CACCT:C	acceptor_loss	1.0000
1:6599451:ACCTG:A	acceptor_loss	1.0000
1:6599454:T:A	acceptor_loss	1.0000
1:6601794:CA:C	donor_loss	1.0000
1:6601795:A:AC	donor_gain	1.0000
1:6601795:AC:A	donor_gain	1.0000
1:6601795:ACC:A	donor_gain	1.0000
1:6601796:C:CC	donor_gain	1.0000
1:6601796:CC:C	donor_gain	1.0000
1:6601796:CCC:C	donor_gain	1.0000
1:6601796:CCCGT:C	donor_gain	1.0000

AlphaMissense

3853 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:6599388:C:A	W362C	1.000
1:6599388:C:G	W362C	1.000
1:6599390:A:G	W362R	1.000
1:6599390:A:T	W362R	1.000
1:6593541:A:G	W540R	0.999
1:6593541:A:T	W540R	0.999
1:6593603:C:T	G519E	0.999
1:6593606:C:T	G518E	0.999
1:6595511:A:G	W492R	0.999
1:6595511:A:T	W492R	0.999
1:6595532:A:C	Y485D	0.999
1:6599132:A:G	W448R	0.999
1:6599132:A:T	W448R	0.999
1:6599268:C:A	W402C	0.999
1:6599268:C:G	W402C	0.999
1:6599270:A:G	W402R	0.999
1:6599270:A:T	W402R	0.999
1:6599291:A:C	Y395D	0.999
1:6599359:C:G	R372P	0.999
1:6599389:C:G	W362S	0.999
1:6599411:A:C	Y355D	0.999
1:6599452:C:A	G341V	0.999
1:6599452:C:T	G341D	0.999
1:6601878:A:G	W314R	0.999
1:6601878:A:T	W314R	0.999
1:6602481:C:G	A113P	0.999
1:6602539:G:C	F93L	0.999
1:6602539:G:T	F93L	0.999
1:6602541:A:G	F93L	0.999
1:6602624:A:G	F65S	0.999

dbSNP variants (sampled 300 via entrez): RS1000220865 (1:6603100 C>G), RS1000670006 (1:6599633 G>A), RS1000964584 (1:6604168 A>T), RS1000971088 (1:6592391 C>T), RS1001071491 (1:6597143 C>A,G,T), RS1001173350 (1:6599870 A>C), RS1001276839 (1:6596711 G>A,C), RS1001378943 (1:6591750 G>A,C), RS1001625097 (1:6596430 G>A,T), RS1001853288 (1:6602881 G>A), RS1001919548 (1:6603650 G>C), RS1002006699 (1:6598473 G>C), RS1002078784 (1:6598247 C>T), RS1002354139 (1:6600945 G>A), RS1002512684 (1:6604852 G>C)

Disease associations

OMIM: gene MIM:616262 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): ependymoma (MONDO:0016698)

Orphanet (1): Ependymoma (Orphanet:251636)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90000025_894	Appendicular lean mass	3.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196128 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

77 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	5
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases abundance, increases expression, affects methylation, affects cotreatment	3
Air Pollutants	affects expression, affects cotreatment, decreases expression, increases abundance, increases oxidation	3
Arsenic	affects methylation, increases abundance, increases expression, affects cotreatment	3
Estradiol	affects expression, increases expression	3
Valproic Acid	affects expression, affects cotreatment, increases expression	3
Acetaminophen	increases expression	2
Ozone	increases abundance, affects expression, affects cotreatment, decreases expression, increases oxidation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	increases abundance, affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
bisphenol F	decreases methylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
bisphenol A	affects expression	1
sodium arsenate	increases abundance, increases expression	1
beta-lapachone	increases expression	1
sodium bichromate	increases expression	1
sulforaphane	increases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
sulindac sulfide	increases expression	1
potassium chromate(VI)	increases expression, affects cotreatment	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
CHEMBL6094271	Binding	Binding affinity to KLHL21 (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)

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

Trial	Phase	Status	Title
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01096368	PHASE3	COMPLETED	Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
NCT00003479	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Ependymoma
NCT00520936	PHASE2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01088035	PHASE2	TERMINATED	Carboplatin as a Radiosensitizer in Treating Childhood Ependymoma
NCT01247922	PHASE2	TERMINATED	Single-agent Erlotinib in Patients Previously Treated With Oral Etoposide in Protocol OSI-774-205
NCT01288235	PHASE2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01295944	PHASE2	COMPLETED	Carboplatin and Bevacizumab for Recurrent Ependymoma
NCT01356290	PHASE2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
NCT01836549	PHASE2	TERMINATED	Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors
NCT02125786	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT03095248	PHASE2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03173950	PHASE2	COMPLETED	Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
NCT03194906	PHASE2	COMPLETED	Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT03727841	PHASE2	TERMINATED	Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma
NCT04049669	PHASE2	ACTIVE_NOT_RECRUITING	Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04374305	PHASE2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04743661	PHASE2	ACTIVE_NOT_RECRUITING	131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma
NCT06804655	PHASE2	NOT_YET_RECRUITING	Pharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07424092	PHASE2	RECRUITING	Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors
NCT00634231	PHASE1	COMPLETED	A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors
NCT00994071	PHASE1	COMPLETED	A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors
NCT01171469	PHASE1	COMPLETED	Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
NCT01331135	PHASE1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT01498783	PHASE1	COMPLETED	Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma