KCTD11

Summary

KCTD11 (potassium channel tetramerization domain containing 11, HGNC:21302) is a protein-coding gene on chromosome 17p13.1, encoding BTB/POZ domain-containing protein KCTD11 (Q693B1). Plays a role as a marker and a regulator of neuronal differentiation; Up-regulated by a variety of neurogenic signals, such as retinoic acid, epidermal growth factor/EGF and NGFB/nerve growth factor.

Enables identical protein binding activity. Predicted to be involved in positive regulation of neuron differentiation. Predicted to act upstream of or within negative regulation of neuroblast proliferation; negative regulation of smoothened signaling pathway; and nervous system development. Predicted to be located in cytoplasm.

Source: NCBI Gene 147040 — RefSeq curated summary.

At a glance

• Gene–disease (curated): renal tubular dysgenesis of genetic origin (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 265 total — 8 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_001363642

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21302
Approved symbol	KCTD11
Name	potassium channel tetramerization domain containing 11
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	REN, KCASH1
Ensembl gene	ENSG00000213859
Ensembl biotype	protein_coding
OMIM	609848
Entrez	147040

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000333751, ENST00000576980

RefSeq mRNA: 2 — MANE Select: NM_001363642 NM_001002914, NM_001363642

CCDS: CCDS32545, CCDS92247

Canonical transcript exons

ENST00000333751 — 1 exons

Exon	Start	End
ENSE00001330829	7352162	7354944

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 95.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8596 / max 349.0969, expressed in 1753 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159154	12.3228	1744
159156	2.0564	656
159155	0.8257	411
159157	0.2869	66
159158	0.1887	101
159159	0.1790	99

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	95.53	gold quality
tibial nerve	UBERON:0001323	89.00	gold quality
esophagus mucosa	UBERON:0002469	87.95	gold quality
skin of leg	UBERON:0001511	87.48	gold quality
skin of abdomen	UBERON:0001416	87.35	gold quality
zone of skin	UBERON:0000014	87.34	gold quality
vagina	UBERON:0000996	87.04	gold quality
esophagus	UBERON:0001043	84.36	gold quality
ectocervix	UBERON:0012249	84.24	gold quality
right coronary artery	UBERON:0001625	83.56	gold quality
granulocyte	CL:0000094	83.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.64	gold quality
descending thoracic aorta	UBERON:0002345	82.51	gold quality
thoracic aorta	UBERON:0001515	81.95	gold quality
ascending aorta	UBERON:0001496	81.81	gold quality
uterine cervix	UBERON:0000002	81.27	gold quality
popliteal artery	UBERON:0002250	80.59	gold quality
tibial artery	UBERON:0007610	80.59	gold quality
stromal cell of endometrium	CL:0002255	80.50	gold quality
left coronary artery	UBERON:0001626	80.49	gold quality
apex of heart	UBERON:0002098	80.38	gold quality
lower esophagus	UBERON:0013473	80.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.22	gold quality
minor salivary gland	UBERON:0001830	79.85	gold quality
myometrium	UBERON:0001296	79.82	gold quality
saliva-secreting gland	UBERON:0001044	79.59	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.58	gold quality
placenta	UBERON:0001987	79.57	gold quality
islet of Langerhans	UBERON:0000006	78.59	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.45	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): SP1

miRNA regulators (miRDB)

36 targeting KCTD11, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-3620-3P	97.78	64.88	772
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-3649	96.85	64.10	340
HSA-MIR-656-5P	96.82	67.67	372

Literature-anchored findings (GeneRIF, showing 6)

• Results identify REN(KCTD11) as a suppressor of Hedgehog signaling and suggest that its inactivation might lead to a deregulation of the tumor-promoting Hedgehog pathway in medulloblastoma. (PMID:15249678)
• findings identify KCTD11 as a widely down-regulated gene in human cancers, and provide a basis to understand how its expression might be deregulated in tumor cells (PMID:20591193)
• the protein is expressed in two alternative variants: a short previously characterized form (sKCTD11) composed by 232 amino acids and a longer variant (lKCTD11) which contains an N-terminal extension of 39 residues. (PMID:21237243)
• Our study demonstrates and supports that KCTD11, as well as negatively regulated downstream effectors belonging to Hh signaling, plays a role in prostate cancer pathogenesis. (PMID:25045667)
• KCTD11 inhibits progression of lung cancer by binding to beta-catenin to regulate the activity of the Wnt and Hippo pathways. (PMID:34453479)
• SALL4 is a CRL3[REN/KCTD11] substrate that drives Sonic Hedgehog-dependent medulloblastoma. (PMID:38062245)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kctd11	ENSMUSG00000046731
rattus_norvegicus	Kctd11	ENSRNOG00000015669
drosophila_melanogaster	twz	FBGN0034636
caenorhabditis_elegans	F32B4.5	WBGENE00009315

Paralogs (13): KCTD1 (ENSG00000134504), KCTD14 (ENSG00000151364), KCTD15 (ENSG00000153885), KCTD18 (ENSG00000155729), KCTD6 (ENSG00000168301), KCTD19 (ENSG00000168676), KCTD12 (ENSG00000178695), KCTD4 (ENSG00000180332), KCTD16 (ENSG00000183775), KCTD8 (ENSG00000183783), KCTD21 (ENSG00000188997), KCNRG (ENSG00000198553), KCTD7 (ENSG00000243335)

Protein

Protein identifiers

BTB/POZ domain-containing protein KCTD11 — Q693B1 (reviewed: Q693B1)

Alternative names: KCASH1 protein, Potassium channel tetramerization domain-containing protein 11, RING-type E3 ubiquitin transferase subunit KCTD11

All UniProt accessions (3): A0A158RFT7, A0A2U3TZI5, Q693B1

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role as a marker and a regulator of neuronal differentiation; Up-regulated by a variety of neurogenic signals, such as retinoic acid, epidermal growth factor/EGF and NGFB/nerve growth factor. Induces apoptosis, growth arrest and the expression of cyclin-dependent kinase inhibitor CDKN1B. Plays a role as a tumor repressor and inhibits cell growth and tumorigenicity of medulloblastoma (MDB). Acts as a probable substrate-specific adapter for a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex towards HDAC1. Functions as antagonist of the Hedgehog pathway on cell proliferation and differentiation by affecting the nuclear transfer of transcription factor GLI1, thus maintaining cerebellar granule cells in undifferentiated state, this effect probably occurs via HDAC1 down-regulation, keeping GLI1 acetylated and inactive. When knock-down, Hedgehog antagonism is impaired and proliferation of granule cells is sustained. Activates the caspase cascade.

Subunit / interactions. Homopentamer. Interacts with KCTD6 and KCTD21; KCTD11 and KCTD6 or KCTD21 may associate in pentameric assemblies. Component of the BCR(KCTD11) E3 ubiquitin ligase complex, at least composed of CUL3 and KCTD11 and RBX1. Interacts (via BTB domain) with CUL3; initially a 4:4 stoichiometry has been reported, however, electron microscopy revealed pentameric states of the BTB domain.

Tissue specificity. Higher expression in cerebellum than in whole brain and lower expression in medulloblastoma.

Domain organisation. The BTB domain is required for growth-suppressing properties.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. Haploinsufficiency of KCTD11 may be a cause of development of medulloblastoma (MDB). MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. An allelic deletion involving genes from chromosome region 17p11.2-pter, sometimes restricted to 17p13.2-13.3, occurs in up to 50% of MDB. Non-AUG start codon.

Isoforms (2)

UniProt ID	Names	Canonical?
Q693B1-1	1, sKCTD11	yes
Q693B1-2	2, lKCTD11

RefSeq proteins (2): NP_001002914, NP_001350571* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003131	T1-type_BTB	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR045763	KCTD11/21_C	Domain

Pfam: PF02214, PF19329

UniProt features (4 total): chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q693B1-F1	85.00	0.56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 341 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GGTGTGT_MIR329, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_IMMOBILIZATION_STRESS, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_NEUROGENESIS

GO Biological Process (12): smoothened signaling pathway (GO:0007224), neuroblast proliferation (GO:0007405), negative regulation of neuroblast proliferation (GO:0007406), neuroblast differentiation (GO:0014016), protein ubiquitination (GO:0016567), neuron differentiation (GO:0030182), positive regulation of neuron differentiation (GO:0045666), negative regulation of smoothened signaling pathway (GO:0045879), protein homooligomerization (GO:0051260), nervous system development (GO:0007399), monoatomic ion transmembrane transport (GO:0034220), regulation of cell population proliferation (GO:0042127)

GO Molecular Function (3): transferase activity (GO:0016740), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
generation of neurons	3
cell differentiation	2
cell surface receptor signaling pathway	1
neural precursor cell proliferation	1
neuroblast proliferation	1
negative regulation of neurogenesis	1
regulation of neuroblast proliferation	1
negative regulation of neural precursor cell proliferation	1
protein modification by small protein conjugation	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
negative regulation of signal transduction	1
protein complex oligomerization	1
system development	1
monoatomic ion transport	1
transmembrane transport	1
cell population proliferation	1
regulation of cellular process	1
catalytic activity	1
protein binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

394 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCTD11	CUL3	Q13618	945
KCTD11	KCTD5	Q9NXV2	762
KCTD11	KCTD17	Q8N5Z5	689
KCTD11	KCTD8	Q6ZWB6	680
KCTD11	KCTD12	Q96CX2	667
KCTD11	GLI1	P08151	659
KCTD11	KCTD9	Q7L273	646
KCTD11	NEUROG1	Q92886	637
KCTD11	KCTD3	Q9Y597	625
KCTD11	NEUROD1	Q13562	607
KCTD11	KCTD10	Q9H3F6	588
KCTD11	KCTD2	Q14681	581
KCTD11	KCTD13	Q8WZ19	550
KCTD11	SHKBP1	Q8TBC3	549
KCTD11	KCTD20	Q7Z5Y7	533

IntAct

5 interactions, top by confidence:

A	B	Type	Score
KCTD11	KCTD11	psi-mi:“MI:0407”(direct interaction)	0.520
KCTD6	POLRMT	psi-mi:“MI:0914”(association)	0.350
KCTD6	PXDNL	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): HDAC1 (Biochemical Activity), CUL3 (Reconstituted Complex), KCTD11 (Affinity Capture-Western), KCTD11 (Affinity Capture-Western), KCTD11 (Affinity Capture-MS), KCTD11 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), KCTD11 (Reconstituted Complex), KCTD11 (Reconstituted Complex), KCTD11 (Affinity Capture-Western), KCTD11 (Affinity Capture-Western), KCTD11 (Reconstituted Complex), CUL3 (Affinity Capture-MS), RBX1 (Affinity Capture-MS), KCTD15 (Affinity Capture-MS)

ESM2 similar proteins: A3KMV1, A5PKG7, A9ULR9, B5DEL1, D5SHR0, O14512, O15021, O42406, O60682, O95343, P05433, P28704, P97287, Q07820, Q0VD00, Q0VDT2, Q14681, Q29RJ0, Q2T9W0, Q5RBI7, Q5U2Z0, Q5VWQ0, Q5XUX0, Q62233, Q693B1, Q69ZH9, Q6NZR2, Q6PI47, Q7RTV3, Q7YRZ9, Q811L6, Q8BFX3, Q8BGV7, Q8CEZ0, Q8HYS5, Q8K0E1, Q8N5Z5, Q8TBC3, Q8VC57, Q8VHQ2

Diamond homologs: A3KMV1, A4IFB4, A5PKG7, A6H6X4, B1WC97, B5DEL1, D5SHR0, G5EFC3, O65555, P0C5J9, P15388, P17971, P17972, P25122, P48547, P59994, P59995, Q01956, Q03607, Q03719, Q0VD00, Q0VFV7, Q14003, Q14681, Q29RJ0, Q2HJ48, Q2TUM3, Q3URF8, Q4G0X4, Q50H33, Q52PG9, Q54KH0, Q5DTY9, Q5M956, Q5XJ34, Q5ZJP7, Q62897, Q63881, Q63959, Q68DU8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
KCTD11	“down-regulates activity”	GLI1

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	6
Uncertain significance	158
Likely benign	43
Benign	27

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1252080	NM_000537.4(REN):c.299_300del (p.Lys100fs)	Pathogenic
13122	NM_000537.4(REN):c.1159C>T (p.Arg387Ter)	Pathogenic
13124	NM_000537.4(REN):c.689G>A (p.Arg230Lys)	Pathogenic
2423261	NC_000001.10:g.(?204130400)(204135421_?)del	Pathogenic
3653918	NM_000537.4(REN):c.951dup (p.Leu318fs)	Pathogenic
3696631	NM_000537.4(REN):c.415A>T (p.Lys139Ter)	Pathogenic
50210	NM_000537.4(REN):c.127C>T (p.Arg43Ter)	Pathogenic
50211	NM_000537.4(REN):c.404C>A (p.Ser135Tyr)	Pathogenic
2131200	NM_000537.4(REN):c.249+1G>T	Likely pathogenic
3384161	NM_000537.4(REN):c.1079dup (p.Leu361fs)	Likely pathogenic
3577981	NM_000537.4(REN):c.1172_1173del (p.Thr391fs)	Likely pathogenic
3578102	NM_000537.4(REN):c.250-1del	Likely pathogenic
3899970	NM_000537.4(REN):c.799del (p.Trp267fs)	Likely pathogenic
562339	NM_000537.4(REN):c.116T>A (p.Met39Lys)	Likely pathogenic

SpliceAI

1309 predictions. Top by Δscore:

Variant	Effect	Δscore
1:204155915:CATA:C	acceptor_gain	1.0000
1:204155917:TA:T	acceptor_gain	1.0000
1:204155919:C:CC	acceptor_gain	1.0000
1:204156160:C:A	donor_gain	1.0000
1:204156176:A:AC	donor_gain	1.0000
1:204156177:C:CC	donor_gain	1.0000
1:204156177:CAT:C	donor_gain	1.0000
1:204156675:ACC:A	donor_gain	1.0000
1:204156676:CCC:C	donor_gain	1.0000
1:204159394:CCCAC:C	donor_loss	1.0000
1:204159395:CCACC:C	donor_loss	1.0000
1:204159396:CACC:C	donor_loss	1.0000
1:204159397:AC:A	donor_loss	1.0000
1:204159398:C:CA	donor_loss	1.0000
1:204159423:T:TA	donor_gain	1.0000
1:204160558:A:AC	donor_gain	1.0000
1:204160559:C:CC	donor_gain	1.0000
1:204160675:TACA:T	acceptor_gain	1.0000
1:204160677:CA:C	acceptor_gain	1.0000
1:204160679:C:CC	acceptor_gain	1.0000
1:204162006:CACT:C	donor_loss	1.0000
1:204162007:ACTC:A	donor_loss	1.0000
1:204162009:TCA:T	donor_loss	1.0000
1:204162010:CAC:C	donor_loss	1.0000
1:204162011:A:AC	donor_gain	1.0000
1:204162011:A:T	donor_loss	1.0000
1:204162011:ACGT:A	donor_gain	1.0000
1:204162011:ACGTC:A	donor_gain	1.0000
1:204162012:C:CT	donor_gain	1.0000
1:204162012:CG:C	donor_gain	1.0000

AlphaMissense

1721 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7353039:T:C	F33L	0.998
17:7353041:C:A	F33L	0.998
17:7353041:C:G	F33L	0.998
17:7353064:G:T	R41M	0.998
17:7353057:T:C	F39L	0.997
17:7353059:C:A	F39L	0.997
17:7353059:C:G	F39L	0.997
17:7353064:G:C	R41T	0.997
17:7353129:T:C	F63L	0.997
17:7353131:C:A	F63L	0.997
17:7353131:C:G	F63L	0.997
17:7353019:T:A	I26N	0.996
17:7353568:T:C	F209S	0.996
17:7353028:A:T	D29V	0.995
17:7353123:G:C	A61P	0.995
17:7353417:T:A	W159R	0.995
17:7353417:T:C	W159R	0.995
17:7353419:G:C	W159C	0.995
17:7353419:G:T	W159C	0.995
17:7353056:T:A	N38K	0.994
17:7353056:T:G	N38K	0.994
17:7353065:G:C	R41S	0.994
17:7353065:G:T	R41S	0.994
17:7353112:T:A	L57H	0.994
17:7353039:T:A	F33I	0.993
17:7353040:T:C	F33S	0.993
17:7353529:T:C	F196S	0.993
17:7353567:T:C	F209L	0.993
17:7353569:C:A	F209L	0.993
17:7353569:C:G	F209L	0.993

dbSNP variants (sampled 300 via entrez): RS1000335578 (17:7354528 G>C,T), RS1000430496 (17:7354202 T>C), RS1000706354 (17:7354589 A>G), RS1000987455 (17:7353345 G>A), RS1001348148 (17:7353134 C>A,T), RS1001420336 (17:7352750 A>C,T), RS1002349489 (17:7351918 G>A), RS1002382333 (17:7350358 A>C,G,T), RS1003048018 (17:7352892 G>A,C,T), RS1003100168 (17:7352540 G>A,T), RS1004105750 (17:7354209 G>A,T), RS1004200593 (17:7353891 T>C,G), RS1006219566 (17:7352334 C>G,T), RS1006252048 (17:7352188 G>A), RS1007044326 (17:7352208 G>C,T)

Disease associations

OMIM: gene MIM:609848 | disease phenotypes: MIM:267430, MIM:613092, MIM:300978

GenCC curated gene-disease

Disease	Classification	Inheritance
familial juvenile hyperuricemic nephropathy type 2	Definitive	Autosomal dominant
renal tubular dysgenesis of genetic origin	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
renal tubular dysgenesis of genetic origin	Definitive	AR
familial juvenile hyperuricemic nephropathy type 2	Definitive	AD

Mondo (7): renal tubular dysgenesis of genetic origin (MONDO:0009970), familial juvenile hyperuricemic nephropathy type 2 (MONDO:0013128), renal tubular dysgenesis (MONDO:0017609), hepatoblastoma (MONDO:0018666), kidney disorder (MONDO:0005240), intellectual disability, X-linked 61 (MONDO:0010506), nephrotic syndrome (MONDO:0005377)

Orphanet (4): REN-related autosomal dominant tubulointerstitial kidney disease (Orphanet:217330), Renal tubular dysgenesis of genetic origin (Orphanet:97369), Renal tubular dysgenesis (Orphanet:3033), Hepatoblastoma (Orphanet:449)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000079	Abnormality of the urinary system
HP:0000089	Renal hypoplasia
HP:0000092	Renal tubular atrophy
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000252	Microcephaly
HP:0001562	Oligohydramnios
HP:0001903	Anemia
HP:0002009	Potter facies
HP:0002089	Pulmonary hypoplasia
HP:0002093	Respiratory insufficiency
HP:0002149	Hyperuricemia
HP:0002615	Hypotension
HP:0004492	Widely patent fontanelles and sutures
HP:0004719	Hyperechogenic kidneys
HP:0005576	Tubulointerstitial fibrosis
HP:0008660	Renotubular dysgenesis
HP:0012622	Chronic kidney disease
HP:0100519	Anuria

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST006190_4	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-10
GCST006190_54	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-08
GCST006192_52	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	8.000000e-11
GCST006192_75	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-12
GCST006193_37	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	9.000000e-11
GCST006193_75	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	9.000000e-09
GCST006195_19	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-11
GCST006195_69	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-12
GCST008359_1	Response to cognitive-behavioural therapy in anxiety disorder	7.000000e-07
GCST009731_72	Blood protein levels in cardiovascular risk	4.000000e-17

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0007820	cognitive behavioural therapy
EFO:0010616	renin measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D018197	Hepatoblastoma	C04.557.435.380
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
C567760	Hyperuricemic Nephropathy, Familial Juvenile 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630837 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.30	Kd	497	nM	CHEMBL4635266

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-carboxy-2-[[(2S)-4-carboxy-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2,4-diamino-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]butanoyl]amino]butanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]pentanoyl]amino]-4-oxobutanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]hexanoic acid	1655992: Binding affinity to recombinant N-terminal poly His-Trx tagged KCTD11 (15 to 115 residues) (unknown origin) expressed in Escherichia coli assessed as inhibition of KCTD11/cullin3a protein-protein interaction by fluorescence polarization assay	kd	0.4970	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	4
Aflatoxin B1	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Cisplatin	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Niclosamide	increases expression	1
Oxygen	increases expression	1
Silver	increases expression	1
Smoke	decreases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases 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
CHEMBL4616365	Binding	Binding affinity to recombinant N-terminal poly His-Trx tagged KCTD11 (15 to 115 residues) (unknown origin) expressed in Escherichia coli assessed as inhibition of KCTD11/cullin3a protein-protein interaction by fluorescence polarization ass	HOPPI-NMR: Hot-Peptide-Based Screening Assay for Inhibitors of Protein-Protein Interactions by NMR. — ACS Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia