STK36

Summary

STK36 (serine/threonine kinase 36, HGNC:17209) is a protein-coding gene on chromosome 2q35, encoding Serine/threonine-protein kinase 36 (Q9NRP7). Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors.

This gene encodes a member of the serine/threonine kinase family of enzymes. This family member is similar to a Drosophila protein that plays a key role in the Hedgehog signaling pathway. This human protein is a positive regulator of the GLI zinc-finger transcription factors. Knockout studies of the homologous mouse gene suggest that defects in this human gene may lead to congenital hydrocephalus, possibly due to a functional defect in motile cilia. Because Hedgehog signaling is frequently activated in certain kinds of gastrointestinal cancers, it has been suggested that this gene is a target for the treatment of these cancers. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 27148 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliary dyskinesia, primary, 46 (Moderate, ClinGen) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 304 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 54
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015690

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17209
Approved symbol	STK36
Name	serine/threonine kinase 36
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1278, FU
Ensembl gene	ENSG00000163482
Ensembl biotype	protein_coding
OMIM	607652
Entrez	27148

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 16 protein_coding, 8 retained_intron, 3 nonsense_mediated_decay

ENST00000295709, ENST00000392105, ENST00000414413, ENST00000419433, ENST00000422778, ENST00000424080, ENST00000440309, ENST00000455724, ENST00000462031, ENST00000468026, ENST00000470568, ENST00000473557, ENST00000473681, ENST00000480709, ENST00000486644, ENST00000492486, ENST00000870275, ENST00000870276, ENST00000870277, ENST00000870278, ENST00000925594, ENST00000925595, ENST00000925596, ENST00000925597, ENST00000925598, ENST00000955186, ENST00000955187

RefSeq mRNA: 3 — MANE Select: NM_015690 NM_001243313, NM_001369423, NM_015690

CCDS: CCDS2421, CCDS58750

Canonical transcript exons

ENST00000295709 — 27 exons

Exon	Start	End
ENSE00001075130	218676029	218676278
ENSE00001075146	218679168	218679261
ENSE00001075147	218692583	218692710
ENSE00001075148	218679893	218680080
ENSE00001075172	218696527	218696601
ENSE00001075173	218697039	218697213
ENSE00001348591	218692143	218692293
ENSE00001348605	218685085	218685228
ENSE00001348609	218680603	218680702
ENSE00001348819	218679560	218679729
ENSE00001348829	218675343	218675473
ENSE00001898194	218672086	218672215
ENSE00001936195	218701866	218702715
ENSE00003461813	218698602	218699348
ENSE00003461953	218694525	218694635
ENSE00003477773	218688697	218688876
ENSE00003492706	218697463	218697610
ENSE00003493612	218672741	218672913
ENSE00003505708	218693895	218693983
ENSE00003526890	218694264	218694327
ENSE00003572489	218673625	218673765
ENSE00003572927	218689859	218689956
ENSE00003616832	218690450	218690555
ENSE00003643600	218697854	218698001
ENSE00003665872	218673879	218673956
ENSE00003667405	218693240	218693344
ENSE00003668942	218693723	218693821

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 98.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3869 / max 184.4938, expressed in 1727 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25367	3.9667	1492
25365	3.4403	1474
25366	0.9702	582
25370	0.0096	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.82	gold quality
adenohypophysis	UBERON:0002196	97.32	gold quality
left testis	UBERON:0004533	97.28	gold quality
right testis	UBERON:0004534	97.27	gold quality
pituitary gland	UBERON:0000007	96.49	gold quality
right lobe of thyroid gland	UBERON:0001119	96.42	gold quality
right ovary	UBERON:0002118	96.39	gold quality
metanephros cortex	UBERON:0010533	95.75	gold quality
right adrenal gland cortex	UBERON:0035827	95.75	gold quality
left ovary	UBERON:0002119	95.73	gold quality
left lobe of thyroid gland	UBERON:0001120	95.72	gold quality
right adrenal gland	UBERON:0001233	95.70	gold quality
testis	UBERON:0000473	95.67	gold quality
body of uterus	UBERON:0009853	95.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.06	gold quality
body of pancreas	UBERON:0001150	95.01	gold quality
thyroid gland	UBERON:0002046	94.86	gold quality
oviduct epithelium	UBERON:0004804	94.84	gold quality
stromal cell of endometrium	CL:0002255	94.53	gold quality
endocervix	UBERON:0000458	94.47	gold quality
cerebellar hemisphere	UBERON:0002245	94.25	gold quality
cerebellar cortex	UBERON:0002129	94.09	gold quality
left adrenal gland cortex	UBERON:0035825	93.90	gold quality
left adrenal gland	UBERON:0001234	93.74	gold quality
right frontal lobe	UBERON:0002810	93.69	gold quality
left uterine tube	UBERON:0001303	93.59	gold quality
gall bladder	UBERON:0002110	93.57	gold quality
ovary	UBERON:0000992	93.29	gold quality
fallopian tube	UBERON:0003889	93.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.10	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.47
E-ENAD-17	no	462.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PATZ1

miRNA regulators (miRDB)

39 targeting STK36, 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-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-6818-5P	97.50	67.10	1167

Literature-anchored findings (GeneRIF, showing 4)

• The FU gene and its genomic structure was identified. (PMID:15268766)
• Fu ubiquitination and cleavage is one of the key elements connecting the MID1-PP2A protein complex with GLI3 activity control (PMID:25278022)
• Data identified homozygous loss-of-function mutations in STK36 in one PCD-affected individual with situs solitus. Transmission electron microscopy analysis demonstrates that STK36 is required for cilia orientation in human respiratory epithelial cells, with a probable localization of STK36 between the RS and CP. STK36 screening can now be included for this rare and difficult to diagnose PCD subgroup. (PMID:28543983)
• Serine/threonine kinase 36 induced epithelial-mesenchymal transition promotes docetaxel resistance in prostate cancer. (PMID:38184689)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	stk36	ENSDARG00000061095
mus_musculus	Stk36	ENSMUSG00000033276
rattus_norvegicus	Stk36	ENSRNOG00000016913
drosophila_melanogaster	fu	FBGN0001079

Paralogs (1): ULK4 (ENSG00000168038)

Protein

Protein identifiers

Serine/threonine-protein kinase 36 — Q9NRP7 (reviewed: Q9NRP7)

Alternative names: Fused homolog

All UniProt accessions (7): Q9NRP7, A0A140VJW1, C9J1B8, C9JDA4, H7C2A4, H7C2I3, H7C359

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors. Controls the activity of the transcriptional regulators GLI1, GLI2 and GLI3 by opposing the effect of SUFU and promoting their nuclear localization. GLI2 requires an additional function of STK36 to become transcriptionally active, but the enzyme does not need to possess an active kinase catalytic site for this to occur. Required for postnatal development, possibly by regulating the homeostasis of cerebral spinal fluid or ciliary function. Essential for construction of the central pair apparatus of motile cilia.

Subunit / interactions. Interacts with GLI1, GLI2 and GLI3. Interacts with SPAG16 and KIF27.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Cilium axoneme.

Tissue specificity. Expressed at low levels in most fetal tissues, adult ovaries and at high levels in adult testis, where it is localized in germ cells. Expressed in respiratory epithelial cells of the lung.

Disease relevance. Ciliary dyskinesia, primary, 46 (CILD46) [MIM:619436] A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD46 is an autosomal recessive form. No situs abnormalities have been observed. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRP7-1	1	yes
Q9NRP7-2	2

RefSeq proteins (3): NP_001230242, NP_001356352, NP_056505* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site

Pfam: PF00069, PF13646

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (36 total): sequence variant 24, sequence conflict 3, region of interest 2, binding site 2, chain 1, domain 1, mutagenesis site 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRP7-F1	81.22	0.48

Functional residue map

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

Catalytic / active sites (1): 125 (proton acceptor)

Ligand- & substrate-binding residues (2): 10–18; 33

Mutagenesis-validated functional residues (1):

Position	Phenotype
33	no effect on nuclear localization of gli1 or gli2 or on gli-mediated transcription.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 204 (showing top): KEGG_HEDGEHOG_SIGNALING_PATHWAY, EFC_Q6, KEGG_PATHWAYS_IN_CANCER, GGAANCGGAANY_UNKNOWN, NF1_Q6_01, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOBP_HEAD_DEVELOPMENT, GOBP_SMOOTHENED_SIGNALING_PATHWAY, HAND1E47_01, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY

GO Biological Process (11): epithelial cilium movement involved in extracellular fluid movement (GO:0003351), protein phosphorylation (GO:0006468), smoothened signaling pathway (GO:0007224), brain development (GO:0007420), post-embryonic development (GO:0009791), axoneme assembly (GO:0035082), positive regulation of smoothened signaling pathway (GO:0045880), obsolete regulation of DNA-binding transcription factor activity (GO:0051090), cilium assembly (GO:0060271), microtubule-based process (GO:0007017), cell projection organization (GO:0030030)

GO Molecular Function (10): transcription corepressor binding (GO:0001222), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), axoneme (GO:0005930), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein kinase activity	2
cilium movement	1
extracellular transport	1
microtubule-based transport	1
phosphorylation	1
protein modification process	1
cell surface receptor signaling pathway	1
central nervous system development	1
animal organ development	1
head development	1
multicellular organism development	1
multicellular organismal process	1
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
positive regulation of signal transduction	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cellular process	1
cellular component organization	1
transcription coregulator binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1

Protein interactions and networks

STRING

794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STK36	KIF27	Q86VH2	919
STK36	SUFU	Q9UMX1	893
STK36	GLI1	P08151	861
STK36	GLI3	P10071	758
STK36	GLI2	P10070	747
STK36	PTCH2	Q9Y6C5	644
STK36	DPCD	Q9BVM2	610
STK36	SHH	Q15465	605
STK36	PTCH1	Q13635	581
STK36	RSPH9	Q9H1X1	544
STK36	RSPH1	Q8WYR4	543
STK36	KIF7	Q2M1P5	543
STK36	PACRG	Q96M98	492
STK36	PAX3	P23760	490
STK36	ULK4	Q96C45	483

IntAct

41 interactions, top by confidence:

A	B	Type	Score
ULK4	STK36	psi-mi:“MI:0915”(physical association)	0.630
STK36	ULK4	psi-mi:“MI:0915”(physical association)	0.630
DMWD	STK36	psi-mi:“MI:0915”(physical association)	0.560
GFAP	STK36	psi-mi:“MI:0915”(physical association)	0.560
KLF11	STK36	psi-mi:“MI:0915”(physical association)	0.560
SPRED1	STK36	psi-mi:“MI:0915”(physical association)	0.560
ATXN3	STK36	psi-mi:“MI:0915”(physical association)	0.560
SUFU	STK36	psi-mi:“MI:2364”(proximity)	0.540
GLI1	STK36	psi-mi:“MI:2364”(proximity)	0.540
GLI3	STK36	psi-mi:“MI:2364”(proximity)	0.540
SUFU	STK36	psi-mi:“MI:0915”(physical association)	0.540
STK36	SUFU	psi-mi:“MI:0915”(physical association)	0.540
STK36	GLI1	psi-mi:“MI:0915”(physical association)	0.540
GLI3	STK36	psi-mi:“MI:0915”(physical association)	0.540
MAP1LC3B	STK36	psi-mi:“MI:0407”(direct interaction)	0.440
STK36	Gli2	psi-mi:“MI:0915”(physical association)	0.400
CLNK	STK36	psi-mi:“MI:0915”(physical association)	0.370
STK36	FRMPD4	psi-mi:“MI:0915”(physical association)	0.370
STK36	MAST2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (49): STK36 (Affinity Capture-Western), STK36 (Biochemical Activity), STK36 (Affinity Capture-Western), HSP90AA1 (Affinity Capture-MS), STK36 (Two-hybrid), STK36 (Co-purification), GLI1 (Co-localization), SUFU (Co-localization), GLI3 (Co-localization), ARMC6 (Affinity Capture-MS), STK36 (Affinity Capture-MS), STK36 (Synthetic Lethality), STK36 (Affinity Capture-Western), STK36 (Affinity Capture-Western), STK36 (Affinity Capture-Western)

ESM2 similar proteins: A4FU01, A4FUG7, A6NE52, D2HS90, D4A929, O15287, O94761, O95382, P0C025, P29473, P29474, P51617, P70313, P97270, Q05932, Q14296, Q15477, Q1JPD6, Q2LGB3, Q3MHT4, Q3U5Q7, Q3V1L6, Q562E7, Q5M8V2, Q5ND34, Q5PQ04, Q5RA67, Q5RAJ5, Q5XIS1, Q62406, Q69ZM6, Q6ZS72, Q6ZVH7, Q6ZVK8, Q75NR7, Q76MJ5, Q7M733, Q80UU1, Q8BLY7, Q8BTN6

Diamond homologs: A0A7J6K7I9, A0A7J6K7Y0, A0A7J6KD88, A2QHV0, A8XJQ6, C4YRB7, O13839, O14047, O34507, O75011, O80888, O88664, P0CY23, P0CY24, P16912, P27636, P28829, P34722, P41892, P50527, P51956, P51957, P92199, P93025, P9WI62, P9WI63, Q0CL79, Q0KHQ5, Q0WPH8, Q12851, Q12852, Q19192, Q1DB00, Q4P5N0, Q53UA7, Q55CA6, Q55D99, Q55DD4, Q55GV3, Q5AP97

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SMO	up-regulates	STK36	binding
MPG	“down-regulates quantity by destabilization”	STK36	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	174
Likely benign	31
Benign	50

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1179004	NM_015690.5(STK36):c.1399del (p.Glu467fs)	Pathogenic
3780678	NM_015690.5(STK36):c.2758del (p.Gln920fs)	Likely pathogenic
3780679	NM_015690.5(STK36):c.2761+1G>T	Likely pathogenic
4278154	NM_015690.5(STK36):c.2248-2A>C	Likely pathogenic

SpliceAI

4457 predictions. Top by Δscore:

Variant	Effect	Δscore
2:218672880:G:GT	donor_gain	1.0000
2:218673763:G:GT	donor_gain	1.0000
2:218673954:CAG:C	donor_loss	1.0000
2:218673956:GG:G	donor_loss	1.0000
2:218673958:T:G	donor_loss	1.0000
2:218676274:TTAAG:T	donor_loss	1.0000
2:218676275:TAAG:T	donor_loss	1.0000
2:218676276:AAG:A	donor_loss	1.0000
2:218676279:G:T	donor_loss	1.0000
2:218676280:T:G	donor_loss	1.0000
2:218679262:G:GG	donor_gain	1.0000
2:218679300:G:GG	donor_gain	1.0000
2:218680699:TGAGG:T	donor_loss	1.0000
2:218680701:AGG:A	donor_loss	1.0000
2:218680702:GGTGA:G	donor_loss	1.0000
2:218680703:GTG:G	donor_loss	1.0000
2:218680704:T:A	donor_loss	1.0000
2:218688686:A:AG	acceptor_gain	1.0000
2:218688686:AT:A	acceptor_gain	1.0000
2:218688687:T:G	acceptor_gain	1.0000
2:218688687:T:TA	acceptor_gain	1.0000
2:218688693:CCA:C	acceptor_loss	1.0000
2:218688694:CA:C	acceptor_loss	1.0000
2:218688695:A:AT	acceptor_loss	1.0000
2:218688873:GCAG:G	donor_gain	1.0000
2:218688878:T:A	donor_loss	1.0000
2:218689852:T:A	acceptor_gain	1.0000
2:218689853:G:A	acceptor_gain	1.0000
2:218689858:GCA:G	acceptor_gain	1.0000
2:218692140:TA:T	acceptor_loss	1.0000

AlphaMissense

8526 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:218673635:T:C	L32P	1.000
2:218675467:A:T	D143V	1.000
2:218672872:T:C	F15L	0.999
2:218672874:T:A	F15L	0.999
2:218672874:T:G	F15L	0.999
2:218672891:G:A	G21D	0.999
2:218673632:C:A	A31D	0.999
2:218673637:A:G	K33E	0.999
2:218673639:G:C	K33N	0.999
2:218673639:G:T	K33N	0.999
2:218673692:A:T	E51V	0.999
2:218675386:T:C	L116P	0.999
2:218675410:G:C	R124P	0.999
2:218675413:A:C	D125A	0.999
2:218675413:A:T	D125V	0.999
2:218675429:C:A	N130K	0.999
2:218675429:C:G	N130K	0.999
2:218675434:T:C	L132P	0.999
2:218675466:G:C	D143H	0.999
2:218675467:A:C	D143A	0.999
2:218675467:A:G	D143G	0.999
2:218675468:C:A	D143E	0.999
2:218675468:C:G	D143E	0.999
2:218675469:T:C	F144L	0.999
2:218675470:T:C	F144S	0.999
2:218675471:T:A	F144L	0.999
2:218675471:T:G	F144L	0.999
2:218675472:G:A	G145R	0.999
2:218675472:G:C	G145R	0.999
2:218675473:G:A	G145E	0.999

dbSNP variants (sampled 300 via entrez): RS1000101842 (2:218685495 A>C), RS1000314415 (2:218693286 T>A,C), RS1000351464 (2:218675028 T>A,C), RS1000424595 (2:218700971 C>T), RS1000645489 (2:218694797 G>A,C), RS1000728574 (2:218674145 C>A,T), RS1000731113 (2:218703083 A>G,T), RS1000797257 (2:218701409 G>A), RS1000864654 (2:218695223 T>A,C), RS1001012959 (2:218681438 A>C), RS1001095453 (2:218686917 T>C), RS1001164870 (2:218702875 T>A), RS1001206649 (2:218700446 G>A), RS1001252359 (2:218697444 C>G), RS1001262854 (2:218693514 G>A)

Disease associations

OMIM: gene MIM:607652 | disease phenotypes: MIM:619436, MIM:617576

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia	Supportive	Autosomal dominant
ciliary dyskinesia, primary, 46	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 46	Moderate	AR

Mondo (3): ciliary dyskinesia, primary, 46 (MONDO:0030332), spermatogenic failure 18 (MONDO:0054615), primary ciliary dyskinesia (MONDO:0016575)

Orphanet (0):

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000119	Abnormality of the genitourinary system
HP:0000238	Hydrocephalus
HP:0000365	Hearing impairment
HP:0000389	Chronic otitis media
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000510	Rod-cone dystrophy
HP:0000750	Delayed speech and language development
HP:0000924	Abnormality of the skeletal system
HP:0001217	Clubbing
HP:0001627	Abnormal heart morphology
HP:0001669	Transposition of the great arteries
HP:0001696	Situs inversus totalis
HP:0001719	Double outlet right ventricle
HP:0001742	Nasal congestion
HP:0001746	Asplenia
HP:0001748	Polysplenia
HP:0002011	Morphological central nervous system abnormality
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0005301	Persistent left superior vena cava
HP:0005425	Recurrent sinopulmonary infections
HP:0006532	Recurrent pneumonia
HP:0006536	Airway obstruction

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001664_1	Amyotrophic lateral sclerosis	6.000000e-07
GCST004604_83	Hematocrit	6.000000e-18
GCST004615_8	Hemoglobin concentration	2.000000e-11
GCST006661_114	Male-pattern baldness	2.000000e-16
GCST010002_409	Refractive error	2.000000e-17
GCST010083_21	Hemoglobin levels	7.000000e-16
GCST010083_351	Hemoglobin levels	1.000000e-15
GCST011334_3	Body mass index and triglycerides (pairwise)	3.000000e-13
GCST90002384_243	Hemoglobin	4.000000e-25
GCST90002403_123	Red blood cell count	2.000000e-44

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004340	body mass index
EFO:0004530	triglyceride measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4312 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 379,585 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL180022	NERATINIB	4	9,404
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL939	GEFITINIB	4	117,814
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL215152	DEFOSBARASERTIB	2	372
CHEMBL475251	R-406	2	762
CHEMBL558752	RAF-265	2	2,721
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1230122	R-1487	1	42
CHEMBL296468	BMS-387032	1	2,075
CHEMBL494089	GSK-690693	1	2,061
CHEMBL574738	AST-487	1	451

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Unc-51-like kinase (ULK) family

Binding affinities (BindingDB)

11 measured of 11 human assays (11 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole	KD	9.8 nM
4-[4-(4-fluorophenyl)-2-(4-methanesulfinylphenyl)-1H-imidazol-5-yl]pyridine	KD	12 nM
BMS-354825	KD	27 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
BMS-387072	KD	1800 nM
2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide	KD	1900 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM

ChEMBL bioactivities

44 potent at pChembl≥5 of 44 total, top 33 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.75	Kd	180	nM	FORETINIB
6.68	Kd	210	nM	DASATINIB
6.64	Kd	230	nM	R-406
6.58	Kd	260	nM	BMS-387032
6.54	Kd	290	nM	CHEMBL386051
6.48	Kd	330	nM	R-1487
6.33	Kd	470	nM	PAZOPANIB
6.24	Kd	570	nM	BOSUTINIB
6.10	Kd	790	nM	SB-202190
6.07	Kd	860	nM	SB-203580
6.06	Kd	870	nM	FEDRATINIB
5.92	Kd	1200	nM	PELITINIB
5.89	Kd	1300	nM	AST-487
5.89	Kd	1300	nM	SB-203580
5.85	Kd	1400	nM	TAE-684
5.58	Kd	2600	nM	GSK-690693
5.57	Kd	2700	nM	CANERTINIB
5.57	Kd	2700	nM	CHEMBL4564337
5.54	Kd	2900	nM	STAUROSPORINE
5.54	Kd	2900	nM	PLX-4720
5.42	Kd	3800	nM	SB-202190
5.42	Kd	3800	nM	SORAFENIB
5.42	Kd	3800	nM	LESTAURTINIB
5.40	Kd	4000	nM	PELITINIB
5.36	Kd	4400	nM	ERLOTINIB
5.35	Kd	4500	nM	CANERTINIB
5.34	Kd	4600	nM	DEFOSBARASERTIB
5.28	Kd	5300	nM	NERATINIB
5.27	Kd	5400	nM	SORAFENIB
5.24	Kd	5700	nM	GEFITINIB
5.19	Kd	6500	nM	BMS-345541
5.17	Kd	6700	nM	STAUROSPORINE
5.08	Kd	8300	nM	RAF-265

PubChem BioAssay actives

45 with measured affinity, of 202 total; 27 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
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625096: Binding constant for STK36 kinase domain	kd	0.1800	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435562: Binding constant for STK36 kinase domain	kd	0.2100	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625096: Binding constant for STK36 kinase domain	kd	0.2300	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	435562: Binding constant for STK36 kinase domain	kd	0.2600	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625096: Binding constant for STK36 kinase domain	kd	0.2900	uM
6-(2,4-difluorophenoxy)-8-methyl-2-(oxan-4-ylamino)pyrido[2,3-d]pyrimidin-7-one	592377: Inhibition of STK36	kd	0.3300	uM
Pazopanib	435562: Binding constant for STK36 kinase domain	kd	0.4700	uM
Bosutinib	625096: Binding constant for STK36 kinase domain	kd	0.5700	uM
4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]phenol	435562: Binding constant for STK36 kinase domain	kd	0.7900	uM
4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine	256572: Average Binding Constant for STK36; NA=Not Active at 10 uM	kd	0.8600	uM
Fedratinib	625096: Binding constant for STK36 kinase domain	kd	0.8700	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256572: Average Binding Constant for STK36; NA=Not Active at 10 uM	kd	1.2000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435562: Binding constant for STK36 kinase domain	kd	1.3000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625096: Binding constant for STK36 kinase domain	kd	1.4000	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	625096: Binding constant for STK36 kinase domain	kd	2.6000	uM
5-(6-bromo-5-methoxy-1H-indol-3-yl)-2-(1H-pyrrol-2-yl)-1,3-oxazole	1541248: Binding affinity to wild-type human partial length STK36 (M1 to T271 residues) expressed in bacterial expression system by active-site directed competition binding assay based Kinomescan method	kd	2.7000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	256572: Average Binding Constant for STK36; NA=Not Active at 10 uM	kd	2.7000	uM
N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	625096: Binding constant for STK36 kinase domain	kd	2.9000	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	256572: Average Binding Constant for STK36; NA=Not Active at 10 uM	kd	2.9000	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508097: Binding affinity to STK36	kd	3.8000	uM
Sorafenib	435562: Binding constant for STK36 kinase domain	kd	3.8000	uM
Erlotinib	625096: Binding constant for STK36 kinase domain	kd	4.4000	uM
2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide	435562: Binding constant for STK36 kinase domain	kd	4.6000	uM
Neratinib	625096: Binding constant for STK36 kinase domain	kd	5.3000	uM
Gefitinib	625096: Binding constant for STK36 kinase domain	kd	5.7000	uM
N’-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine	625096: Binding constant for STK36 kinase domain	kd	6.5000	uM
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	625096: Binding constant for STK36 kinase domain	kd	8.3000	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
uranyl acetate	affects expression	1
beta-lapachone	increases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lead	increases expression	1
Malathion	decreases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Uranium	affects expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

77 unique, capped per target: 77 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1059368	Binding	Inhibition of STK36 assessed as enzyme activity at 1 uM relative to untreated control	Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and orally bioavailable aminoisoquinoline. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02871778	PHASE2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT07318974	PHASE2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT05737485	PHASE1	COMPLETED	Study Evaluating the Safety and Tolerability of RCT1100 in Healthy and PCD Subjects
NCT06600425	PHASE1	COMPLETED	A Study to Assess the Safety, Tolerability, Ciliary Rescue, and Pharmacodynamics of RCT1100 in Adults With PCD
NCT06633757	PHASE1	COMPLETED	Study of Inhaled RCT1100 in Adults With PCD Caused by Pathogenic Mutations in the DNAI1 Gene to Measure Mucociliary Clearance
NCT04901715	EARLY_PHASE1	COMPLETED	Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
NCT00005650	Not specified	COMPLETED	Genetic Study of Patients With Primary Ciliary Dyskinesia
NCT00323167	Not specified	COMPLETED	Rare Genetic Disorders of the Breathing Airways
NCT00368446	Not specified	COMPLETED	Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease
NCT00450918	Not specified	COMPLETED	Evaluating Progression of and Diagnostic Tools for Primary Ciliary Dyskinesia in Children and Adolescents
NCT00608556	Not specified	COMPLETED	Dyskinesia, Heterotaxy and Congenital Heart Disease
NCT00686309	Not specified	UNKNOWN	Comparison of On-line and Off-line Measurements of Exhaled Nitric Oxide (NO)
NCT00722878	Not specified	COMPLETED	Long-term Lung Function and Disease Progression in Children With Early Onset Primary Ciliary Dyskinesia Lung Disease
NCT00739817	Not specified	UNKNOWN	Screening for Primary Ciliary Dyskinesia Using Nasal Nitric Oxide
NCT00783887	Not specified	COMPLETED	Diagnosis of Primary Ciliary Dyskinesia
NCT00807482	Not specified	RECRUITING	Pathogenesis of Primary Ciliary Dyskinesia (PCD) Lung Disease
NCT01070914	Not specified	UNKNOWN	Early Detection and Characterization of Primary Ciliary Dyskinesia
NCT01155115	Not specified	COMPLETED	Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
NCT01246258	Not specified	COMPLETED	Otolith Function in Patients With Primary Ciliary Dyskinesia
NCT01929356	Not specified	RECRUITING	Chest Physiotherapy and Lung Function in Primary Ciliary Dyskinesia
NCT02389049	Not specified	COMPLETED	Genetics of Primary Ciliary Dyskinesia
NCT02419365	Not specified	RECRUITING	International Primary Ciliary Dyskinesia (PCD) Registry
NCT02699177	Not specified	UNKNOWN	In Vivo Measurements of Nasal Ciliary Beat Frequency by Using Interferometry
NCT02704455	Not specified	NOT_YET_RECRUITING	Registry Study on Primary Ciliary Dyskinesia in Chinese Children
NCT03271840	Not specified	COMPLETED	Registry for Primary Ciliary Dyskinesia
NCT03279965	Not specified	UNKNOWN	MRI in Cystic Fibrosis and Primary Ciliary Dyskinesia
NCT03320382	Not specified	UNKNOWN	Multiple Breath Washout, a Clinimetric Dataset
NCT03370029	Not specified	COMPLETED	Respiratory Muscle Strength, Exercise Capacity and Physical Activity Levels in Children Primary Ciliary Dyskinesia
NCT03494894	Not specified	COMPLETED	Bacteriological Link Between Upper and Lower Airways in Cystic Fibrosis and Primary Ciliary Dyskinesia
NCT03517865	Not specified	ACTIVE_NOT_RECRUITING	International Primary Ciliary Dyskinesia Cohort
NCT03606200	Not specified	RECRUITING	Swiss Primary Ciliary Dyskinesia Registry
NCT03704207	Not specified	RECRUITING	Utility of PCD Diagnostics to Improve Clinical Care
NCT03704896	Not specified	UNKNOWN	PRospective Observational Multicentre Study on VAriability of Lung Function in Stable PCD Patients
NCT03801395	Not specified	COMPLETED	PCD New Gene Discovery
NCT03809091	Not specified	UNKNOWN	WGS of Korean Idiopathic Bronchiectasis
NCT03832491	Not specified	COMPLETED	Effect of Game Based Approach on Oxygenation, Functional Capacity and Quality of Life in Primary Ciliary Dyskinesia
NCT04161313	Not specified	COMPLETED	Respiratory Function, Exercise Capacity and Peripheral Muscle Strength Among Patients With CF, PCD and Healthy Children
NCT04476433	Not specified	COMPLETED	Intervention in Chronic Pediatric Patients and Their Families.
NCT04489472	Not specified	UNKNOWN	The Effect of a Dietary Supplement Rich in Nitric Oxide in Patients Diagnosed With Primary Ciliary Dyskinesia.
NCT04602481	Not specified	RECRUITING	Living With Primary Ciliary Dyskinesia (Living With PCD)