SPOUT1

Summary

SPOUT1 (SPOUT domain containing methyltransferase 1, HGNC:26933) is a protein-coding gene on chromosome 9q34.11, encoding 28S rRNA (uridine-N(3))-methyltransferase (Q5T280). S-adenosyl-L-methionine-dependent RNA methyltransferase. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Enables miRNA binding activity. Involved in maintenance of centrosome location and miRNA processing. Acts upstream of with a positive effect on post-transcriptional regulation of gene expression. Located in kinetochore; mitotic spindle; and spindle pole centrosome.

Source: NCBI Gene 51490 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 6 total
• Phenotypes (HPO): 98
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_016390

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26933
Approved symbol	SPOUT1
Name	SPOUT domain containing methyltransferase 1
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	HSPC109, CENP-32
Ensembl gene	ENSG00000198917
Ensembl biotype	protein_coding
OMIM	617614
Entrez	51490

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 retained_intron

ENST00000361256, ENST00000466556, ENST00000467396, ENST00000467582, ENST00000480366, ENST00000853913, ENST00000940338, ENST00000965410, ENST00000965411, ENST00000965412

RefSeq mRNA: 1 — MANE Select: NM_016390 NM_016390

CCDS: CCDS6913

Canonical transcript exons

ENST00000361256 — 12 exons

Exon	Start	End
ENSE00001143466	128826022	128826152
ENSE00001143487	128828735	128828860
ENSE00001854644	128829745	128829794
ENSE00001907060	128819651	128822833
ENSE00003468974	128826540	128826629
ENSE00003572628	128827032	128827191
ENSE00003590862	128829110	128829155
ENSE00003600139	128824977	128825049
ENSE00003614577	128823747	128823894
ENSE00003616001	128826384	128826433
ENSE00003633502	128824771	128824869
ENSE00003669195	128824072	128824174

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.6084 / max 200.9506, expressed in 1794 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102707	17.6084	1794

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	94.84	gold quality
right lobe of liver	UBERON:0001114	93.41	gold quality
fundus of stomach	UBERON:0001160	92.34	gold quality
apex of heart	UBERON:0002098	92.34	gold quality
mucosa of transverse colon	UBERON:0004991	92.16	gold quality
prostate gland	UBERON:0002367	91.85	gold quality
spleen	UBERON:0002106	91.77	gold quality
lymph node	UBERON:0000029	91.44	gold quality
lower esophagus mucosa	UBERON:0035834	91.34	gold quality
body of stomach	UBERON:0001161	91.09	gold quality
vermiform appendix	UBERON:0001154	90.95	gold quality
esophagus mucosa	UBERON:0002469	90.93	gold quality
liver	UBERON:0002107	90.70	gold quality
right lobe of thyroid gland	UBERON:0001119	90.62	gold quality
prefrontal cortex	UBERON:0000451	90.61	gold quality
right coronary artery	UBERON:0001625	90.23	gold quality
left lobe of thyroid gland	UBERON:0001120	90.22	gold quality
thyroid gland	UBERON:0002046	90.13	gold quality
metanephros cortex	UBERON:0010533	90.09	gold quality
body of pancreas	UBERON:0001150	89.97	gold quality
frontal cortex	UBERON:0001870	89.95	gold quality
esophagus	UBERON:0001043	89.91	gold quality
skin of abdomen	UBERON:0001416	89.88	gold quality
left coronary artery	UBERON:0001626	89.84	gold quality
right adrenal gland	UBERON:0001233	89.82	gold quality
right adrenal gland cortex	UBERON:0035827	89.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.76	gold quality
zone of skin	UBERON:0000014	89.74	gold quality
stomach	UBERON:0000945	89.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.66	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6058	no	95.19
E-ANND-3	no	1.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting SPOUT1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 1)

• CENP-32 appears to be required for centrosomes to integrate into a fully functional spindle that not only nucleates astral microtubules, but also is able to nucleate and bind to kinetochore and central spindle microtubules. (PMID:25657325)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	spout1	ENSDARG00000019707
mus_musculus	Spout1	ENSMUSG00000039660
rattus_norvegicus	Spout1	ENSRNOG00000025711
drosophila_melanogaster	CG12128	FBGN0033473
caenorhabditis_elegans		WBGENE00015160

Protein

Protein identifiers

28S rRNA (uridine-N(3))-methyltransferase — Q5T280 (reviewed: Q5T280)

Alternative names: Centromere protein 32, Kinetochore-associated protein, Methyltransferase C9orf114, Ribosomal RNA methyltransferase SPOUT1, SPOUT domain-containing methyltransferase 1

All UniProt accessions (2): Q5T280, R4GNG4

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent RNA methyltransferase. Specifically methylates the N3 position of a uridine in 28S rRNA. Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase, ensuring proper spindle organization. Also involved in chromosome alignment. May promote centrosome maturation probably by recruiting A-kinase anchor protein AKAP9 to centrosomes in early mitosis. Binds specifically to miRNA MIR145 hairpin, regulates MIR145 expression at a postranscriptional level.

Subunit / interactions. Forms homodimers. Interacts with INCA1.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Chromosome. Centromere. Kinetochore. Microtubule organizing center. Centrosome.

Disease relevance. Neurodevelopmental disorder with poor growth, seizures, and brain abnormalities (NEDGSB) [MIM:621154] An autosomal recessive disorder characterized by varying degrees of developmental delay apparent in early infancy, poor overall growth, short stature, microcephaly, seizures, motor delay often with hypotonia, and mild to severe intellectual disability with speech and language delay. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Depletion with RNAi causes a significant accumulation of cells in later prometaphase with misaligned chromosomes.

Similarity. Belongs to the class IV-like SAM-binding methyltransferase superfamily.

RefSeq proteins (1): NP_057474* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003750	Put_MeTrfase-C9orf114-like	Family
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR029026	tRNA_m1G_MTases_N	Homologous_superfamily
IPR029028	Alpha/beta_knot_MTases	Homologous_superfamily

Pfam: PF02598

Catalyzed reactions (Rhea), 1 shown:

• uridine in 28S rRNA + S-adenosyl-L-methionine = N(3)-methyluridine in 28S rRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:83635)

UniProt features (63 total): sequence variant 20, strand 14, helix 13, binding site 9, region of interest 2, chain 1, compositionally biased region 1, mutagenesis site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4RG1	X-RAY DIFFRACTION	1.86
8QSU	X-RAY DIFFRACTION	2.38
8QSW	X-RAY DIFFRACTION	2.5
8QSV	X-RAY DIFFRACTION	2.62

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T280-F1	88.30	0.66

Functional residue map

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

Ligand- & substrate-binding residues (9): 341; 342; 342; 289; 292; 292; 312; 312; 341

Mutagenesis-validated functional residues (1):

Position	Phenotype
356	decreased methyltransferase activity with gapdh mrna hairpin as substrate. 3-fold decreased affinity for gapdh mrna hair

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 116 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_RNA_METHYLATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_RNA_MODIFICATION, GOBP_MAINTENANCE_OF_LOCATION, MODULE_285, GOCC_CENTROSOME, MODULE_99, GOBP_RRNA_MODIFICATION, GOBP_METHYLATION, GOBP_ORGANELLE_LOCALIZATION, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_RRNA_METHYLATION, GOCC_SPINDLE

GO Biological Process (7): post-transcriptional regulation of gene expression (GO:0010608), miRNA processing (GO:0035196), cell division (GO:0051301), maintenance of centrosome location (GO:0051661), rRNA base methylation (GO:0070475), rRNA processing (GO:0006364), methylation (GO:0032259)

GO Molecular Function (8): RNA binding (GO:0003723), methyltransferase activity (GO:0008168), RNA methyltransferase activity (GO:0008173), miRNA binding (GO:0035198), rRNA (uridine-N3-)-methyltransferase activity (GO:0070042), S-adenosyl-L-methionine binding (GO:1904047), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (9): kinetochore (GO:0000776), spindle pole centrosome (GO:0031616), mitotic spindle (GO:0072686), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	4
regulation of gene expression	1
regulatory ncRNA processing	1
cellular process	1
centrosome localization	1
maintenance of organelle location	1
rRNA methylation	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
metabolic process	1
nucleic acid binding	1
transferase activity, transferring one-carbon groups	1
methyltransferase activity	1
catalytic activity, acting on RNA	1
regulatory RNA binding	1
N-methyltransferase activity	1
rRNA (uridine) methyltransferase activity	1
cation binding	1
sulfur compound binding	1
binding	1
catalytic activity	1
condensed chromosome, centromeric region	1
supramolecular complex	1
spindle pole	1
centrosome	1
spindle	1
chromosomal region	1
intracellular anatomical structure	1
cellular anatomical structure	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

1254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPOUT1	TBC1D13	Q9NVG8	931
SPOUT1	KYAT1	Q16773	906
SPOUT1	ENDOG	Q14249	855
SPOUT1	KNSTRN	Q9Y448	589
SPOUT1	CENPE	Q02224	506
SPOUT1	BUB3	O43684	472
SPOUT1	SLC27A4	Q6P1M0	440
SPOUT1	PPP2CA	P05323	431
SPOUT1	ESPL1	Q14674	420
SPOUT1	NDC80	O14777	418
SPOUT1	SS18L2	Q9UHA2	412
SPOUT1	ZW10	O43264	397
SPOUT1	SKA3	Q8IX90	397
SPOUT1	KNL1	Q8NG31	373
SPOUT1	CDC14A	Q9UNH5	359

IntAct

60 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RBMX2	WDR46	psi-mi:“MI:0914”(association)	0.530
INCA1	SPOUT1	psi-mi:“MI:0915”(physical association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
SPOUT1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
SPOUT1	LSM1	psi-mi:“MI:0915”(physical association)	0.400
SPOUT1	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
SPOUT1	PLK1	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Eif3a	RPSA	psi-mi:“MI:0914”(association)	0.350
TSNAX		psi-mi:“MI:0914”(association)	0.350
Srp72		psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
WRAP73	AKAP8	psi-mi:“MI:0914”(association)	0.350
SNRNP70	SMN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (154): C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), NAF1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS), C9orf114 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D1CLQ4, A0A1D8PF11, A1DAY1, A1K7B9, A4VPP0, A5UJN3, A6VCK1, A9A2Z3, B0WC25, B8GDW0, O01757, O13019, O13672, O14062, O59936, O74322, O97249, P17076, P29453, P37164, P37165, P48589, P49196, P80455, Q016E7, Q02FS8, Q03253, Q09464, Q10950, Q54PX9, Q54U07, Q5ADQ6, Q5ANA1, Q5N127, Q5T280, Q60YI3, Q6XIP0, Q7U8L9, Q84WM9, Q8SSG1

Diamond homologs: A1Z830, O13641, Q10950, Q3UHX9, Q5T280, P53336

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Response of EIF2AK4 (GCN2) to amino acid deficiency	5	12.6×	5e-03
Major pathway of rRNA processing in the nucleolus and cytosol	6	8.4×	5e-03
Metabolism of RNA	8	7.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2485 predictions. Top by Δscore:

Variant	Effect	Δscore
9:128820737:A:AC	acceptor_loss	1.0000
9:128820737:A:AG	acceptor_gain	1.0000
9:128820738:G:GG	acceptor_gain	1.0000
9:128823902:A:C	acceptor_gain	1.0000
9:128824764:T:TA	donor_gain	1.0000
9:128824767:TTA:T	donor_loss	1.0000
9:128824768:TA:T	donor_loss	1.0000
9:128824769:A:AC	donor_gain	1.0000
9:128824769:ACT:A	donor_loss	1.0000
9:128824770:C:CA	donor_gain	1.0000
9:128824770:CT:C	donor_gain	1.0000
9:128824770:CTG:C	donor_gain	1.0000
9:128824770:CTGAG:C	donor_gain	1.0000
9:128824968:T:A	donor_gain	1.0000
9:128824973:ATAC:A	donor_loss	1.0000
9:128824974:TACC:T	donor_loss	1.0000
9:128824975:ACCTG:A	donor_loss	1.0000
9:128824976:C:A	donor_loss	1.0000
9:128825047:CTC:C	acceptor_gain	1.0000
9:128826016:TCCTA:T	donor_loss	1.0000
9:128826017:CCTAC:C	donor_loss	1.0000
9:128826018:CTA:C	donor_loss	1.0000
9:128826019:TAC:T	donor_loss	1.0000
9:128826020:A:T	donor_loss	1.0000
9:128826021:C:CA	donor_loss	1.0000
9:128826150:GCC:G	acceptor_gain	1.0000
9:128826151:CC:C	acceptor_gain	1.0000
9:128826151:CCC:C	acceptor_gain	1.0000
9:128826152:CC:C	acceptor_gain	1.0000
9:128826153:C:CC	acceptor_gain	1.0000

AlphaMissense

2434 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128822830:C:G	A356P	0.999
9:128824804:A:G	W260R	0.999
9:128824804:A:T	W260R	0.999
9:128826041:A:T	V207D	0.999
9:128826092:C:G	R190P	0.999
9:128826395:A:G	L166P	0.999
9:128826424:C:A	R156S	0.999
9:128826424:C:G	R156S	0.999
9:128826425:C:A	R156M	0.999
9:128826425:C:G	R156T	0.999
9:128823757:A:T	I351N	0.998
9:128823765:G:C	S348R	0.998
9:128823765:G:T	S348R	0.998
9:128823767:T:G	S348R	0.998
9:128824123:C:T	G288E	0.998
9:128824801:C:G	G261R	0.998
9:128826087:C:G	G192R	0.998
9:128826152:C:T	G170E	0.998
9:128826428:A:G	L155P	0.998
9:128826545:A:C	C151W	0.998
9:128826547:A:G	C151R	0.998
9:128826561:A:G	L146P	0.998
9:128827095:C:A	R102I	0.998
9:128827095:C:G	R102T	0.998
9:128827098:G:T	A101D	0.998
9:128827107:C:T	G98D	0.998
9:128827167:G:T	A78D	0.998
9:128827172:G:C	S76R	0.998
9:128827172:G:T	S76R	0.998
9:128827174:T:G	S76R	0.998

dbSNP variants (sampled 300 via entrez): RS1000000084 (9:128830830 T>C), RS1000377291 (9:128819721 A>C), RS1000456416 (9:128830467 G>A,C), RS1000742076 (9:128819925 C>T), RS1000825969 (9:128830316 G>C,T), RS1001153686 (9:128830581 C>T), RS1001175443 (9:128830341 A>G), RS1001624899 (9:128830068 T>C), RS1002400913 (9:128824501 G>A), RS1002622021 (9:128827589 C>G,T), RS1002729988 (9:128823539 G>A), RS1002880121 (9:128819336 C>G,T), RS1002889248 (9:128828982 C>A,T), RS1003173173 (9:128827837 G>A,T), RS1003247503 (9:128829267 A>G)

Disease associations

OMIM: gene MIM:617614 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

98 total (30 of 98 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000121	Nephrocalcinosis
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000307	Pointed chin
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000378	Cupped ear
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000518	Cataract
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000555	Leukocoria
HP:0000568	Microphthalmia
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000737	Irritability
HP:0000819	Diabetes mellitus
HP:0000961	Cyanosis
HP:0000969	Edema
HP:0001028	Hemangioma
HP:0001137	Alternating esotropia
HP:0001249	Intellectual disability

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005038_22	Allergic disease (asthma, hay fever or eczema)	3.000000e-09
GCST008129_52	Body mass index	1.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066478 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.45	Kd	3517	nM	CHEMBL5653589
5.40	ED50	4006	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147975: Binding affinity to human C9orf114 incubated for 45 mins by Kinobead based pull down assay	kd	3.5168	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	3
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
bisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	decreases expression, increases abundance, affects cotreatment	1
Ivermectin	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
1-Butanol	increases abundance, affects cotreatment, decreases expression	1
Particulate Matter	increases abundance, affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651017	Binding	Binding affinity to human C9orf114 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder