RBM17

Summary

RBM17 (RNA binding motif protein 17, HGNC:16944) is a protein-coding gene on chromosome 10p15.1, encoding Splicing factor 45 (Q96I25). Splice factor that binds to the single-stranded 3’AG at the exon/intron border and promotes its utilization in the second catalytic step. It is a common-essential gene (DepMap: required in 98.8% of cancer cell lines).

This gene encodes an RNA binding protein. The encoded protein is part of the spliceosome complex and functions in the second catalytic step of mRNA splicing. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 9 and 15.

Source: NCBI Gene 84991 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 38 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_032905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16944
Approved symbol	RBM17
Name	RNA binding motif protein 17
Location	10p15.1
Locus type	gene with protein product
Status	Approved
Aliases	SPF45, MGC14439
Ensembl gene	ENSG00000134453
Ensembl biotype	protein_coding
OMIM	606935
Entrez	84991

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 24 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000379888, ENST00000418631, ENST00000432931, ENST00000437845, ENST00000446108, ENST00000447032, ENST00000465906, ENST00000467080, ENST00000467214, ENST00000476706, ENST00000481147, ENST00000496762, ENST00000910318, ENST00000910319, ENST00000910320, ENST00000910321, ENST00000910322, ENST00000910323, ENST00000910324, ENST00000910325, ENST00000910326, ENST00000910327, ENST00000930036, ENST00000930037, ENST00000930038, ENST00000930039, ENST00000945632, ENST00000945633, ENST00000945634, ENST00000945635

RefSeq mRNA: 2 — MANE Select: NM_032905 NM_001145547, NM_032905

CCDS: CCDS7077

Canonical transcript exons

ENST00000379888 — 12 exons

Exon	Start	End
ENSE00000915068	6101271	6101387
ENSE00000915069	6104931	6105097
ENSE00000915070	6106141	6106238
ENSE00000915071	6108686	6108742
ENSE00001483069	6097048	6097188
ENSE00001907046	6089034	6089193
ENSE00001910979	6115453	6117447
ENSE00002720644	6112210	6112361
ENSE00003517525	6115239	6115311
ENSE00003550780	6114049	6114147
ENSE00003578794	6113508	6113581
ENSE00003635391	6109986	6110127

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.4345 / max 332.3969, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103674	54.5604	1822
103673	1.8741	1229

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	98.63	gold quality
left lobe of thyroid gland	UBERON:0001120	98.57	gold quality
body of uterus	UBERON:0009853	98.54	gold quality
body of pancreas	UBERON:0001150	98.51	gold quality
spleen	UBERON:0002106	98.50	gold quality
right uterine tube	UBERON:0001302	98.49	gold quality
right lobe of thyroid gland	UBERON:0001119	98.48	gold quality
right lung	UBERON:0002167	98.48	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.47	gold quality
upper lobe of left lung	UBERON:0008952	98.44	gold quality
vermiform appendix	UBERON:0001154	98.37	gold quality
left uterine tube	UBERON:0001303	98.34	gold quality
left ovary	UBERON:0002119	98.33	gold quality
left testis	UBERON:0004533	98.32	gold quality
thyroid gland	UBERON:0002046	98.30	gold quality
peritoneum	UBERON:0002358	98.28	gold quality
omental fat pad	UBERON:0010414	98.28	gold quality
right testis	UBERON:0004534	98.26	gold quality
upper lobe of lung	UBERON:0008948	98.25	gold quality
rectum	UBERON:0001052	98.22	gold quality
right ovary	UBERON:0002118	98.22	gold quality
sural nerve	UBERON:0015488	98.19	gold quality
mucosa of stomach	UBERON:0001199	98.18	gold quality
smooth muscle tissue	UBERON:0001135	98.10	gold quality
endocervix	UBERON:0000458	98.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.04	gold quality
transverse colon	UBERON:0001157	97.99	gold quality
minor salivary gland	UBERON:0001830	97.96	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.94	gold quality
ectocervix	UBERON:0012249	97.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6911	no	244.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting RBM17, 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-656-3P	100.00	72.15	2788
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-5697	99.39	67.74	1249

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 14)

• overexpression of SPF45 in HeLa, a cervical carcinoma cell line, resulted in drug resistance to doxorubicin and vincristine (PMID:14578179)
• Resistance to various chemotherapeutics resulting from stable transfection of RBM17 (SPF45) in A2780 ovarian carcinoma cells may be due to effects of SPF45 on transcription and splicing of ERbeta-regulated genes. (PMID:16061639)
• The SPF45 regulates alternative splicing of the apoptosis regulatory gene CD95; 2.1-A crystal structure of SPF45-UHM in complex with a ULM peptide from SF3b155 is reported. (PMID:17589525)
• dephosphorylation of pS776-ATXN1 by PP2A regulates the interaction of ATXN1 with the splicing factors RBM17 and U2AF65 (PMID:21835928)
• identify SPF45 as the first splicing factor regulated by multiple MAP kinase pathways and show effects of both SPF45 overexpression and phosphorylation (PMID:22615491)
• this work provides the structural and molecular basis of the interaction between RBM17 and the phosphorylated form of ATXN1. (PMID:24858692)
• Data show that RNA binding motif protein 17 (RBM17) overexpressed in glioma patients and resulted in the poor prognosis. (PMID:30227940)
• Also our presented results indicate that splicing factors hnRNP A1 and SPF45, previously shown to regulate Fas alternative splicing in normoxic cells, are not involved in hypoxia dependent alternative Fas pre-mRNA splicing regulation in an amount dependent manner. Our observations on hypoxia dependent alternative Fas pre-mRNA splicing regulation indicate a probable involvement of other, yet unidentified splicing factors. (PMID:31002816)
• Exploration of the effects of the CYCLOPS gene RBM17 in hepatocellular carcinoma. (PMID:32497093)
• A 5’-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer. (PMID:34225773)
• SPF45/RBM17-dependent, but not U2AF-dependent, splicing in a distinct subset of human short introns. (PMID:34389706)
• The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors. (PMID:35781533)
• AKT1 phosphorylates RBM17 to promote Sox2 transcription by modulating alternative splicing of FOXM1 to enhance cancer stem cell properties in colorectal cancer cells. (PMID:36520054)
• SAP30BP interacts with RBM17/SPF45 to promote splicing in a subset of human short introns. (PMID:38065098)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm17	ENSDARG00000031346
mus_musculus	Rbm17	ENSMUSG00000037197
rattus_norvegicus	Rbm17	ENSRNOG00000018767
drosophila_melanogaster	Spf45	FBGN0086683
caenorhabditis_elegans		WBGENE00010233

Protein

Protein identifiers

Splicing factor 45 — Q96I25 (reviewed: Q96I25)

Alternative names: 45 kDa-splicing factor, RNA-binding motif protein 17

All UniProt accessions (6): Q96I25, H0Y6J6, Q5W009, Q5W010, Q5W011, Q5W012

UniProt curated annotations — full annotation on UniProt →

Function. Splice factor that binds to the single-stranded 3’AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia.

Subunit / interactions. Binds SXL. Associates with the spliceosome. Interacts with SF3B1, SF1 and U2AF2.

Subcellular location. Nucleus.

RefSeq proteins (2): NP_001139019, NP_116294* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000467	G_patch_dom	Domain
IPR000504	RRM_dom	Domain
IPR003954	RRM_euk-type	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034653	SPF45_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR040052	RBM17	Family

Pfam: PF00076, PF01585

UniProt features (43 total): modified residue 12, cross-link 7, mutagenesis site 5, strand 4, helix 3, compositionally biased region 3, domain 2, turn 2, region of interest 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6HIP	X-RAY DIFFRACTION	1.2
2PE8	X-RAY DIFFRACTION	2
2PEH	X-RAY DIFFRACTION	2.11
5LSO	X-RAY DIFFRACTION	2.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96I25-F1	69.10	0.24

Functional residue map

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

Post-translational modifications (19): 2, 21, 41, 71, 155, 169, 222, 237, 266, 291, 293, 15, 24, 33, 41, 58, 256, 276, 2

Mutagenesis-validated functional residues (5):

Position	Phenotype
319	impairs interaction with sf1; has minor effect on interaction with sf3b1 and u2af2.
319	abolishes interaction with sf3b1, sf1 and u2af2. abolishes regulation of alternative splicing.
375	impairs interaction with sf3b1, sf1 and u2af2. abolishes regulation of alternative splicing.
376	impairs interaction with sf3b1, sf1 and u2af2. abolishes regulation of alternative splicing.
377	impairs interaction with sf1 and u2af2 and abolishes interaction with sf3b1. abolishes regulation of alternative splicin

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9943411	CHD1 and CHD2 subfamily
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 175 (showing top): GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, MORF_ZNF10, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, MORF_EPHA7, MORF_RAB3A, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, GOBP_MRNA_CIS_SPLICING_VIA_SPLICEOSOME, MORF_WNT1, MODULE_48, MODULE_95, MORF_IL9, MORF_DCC

GO Biological Process (6): alternative mRNA splicing, via spliceosome (GO:0000380), mRNA cis splicing, via spliceosome (GO:0045292), RNA splicing, via transesterification reactions (GO:0000375), mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (3): RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), nucleus (GO:0005634), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
CHD chromatin remodelers	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mRNA splicing, via spliceosome	2
RNA processing	2
binding	2
RNA splicing	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
nuclear lumen	1
cellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular membrane-bounded organelle	1
cellular_component	1

Protein interactions and networks

STRING

1666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM17	ATXN1	P54253	966
RBM17	SF3B1	O75533	957
RBM17	CIC	Q96RK0	847
RBM17	U2SURP	O15042	789
RBM17	CHERP	Q8IWX8	785
RBM17	ATXN1L	P0C7T5	698
RBM17	U2AF2	P26368	695
RBM17	RBM39	Q14498	667
RBM17	RBM5	P52756	638
RBM17	PQBP1	O60828	638
RBM17	IL2RA	P01589	630
RBM17	U2AF1	Q01081	600
RBM17	HNRNPC	P07910	582
RBM17	UBQLN4	Q9NRR5	577
RBM17	QKI	Q96PU8	565

IntAct

220 interactions, top by confidence:

A	B	Type	Score
RBM17	SF3B1	psi-mi:“MI:0407”(direct interaction)	0.910
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
DHX15	RBM17	psi-mi:“MI:0915”(physical association)	0.880
RBM17	DHX15	psi-mi:“MI:0915”(physical association)	0.880
SAT1	RBM17	psi-mi:“MI:0915”(physical association)	0.870
RBM17	SAT1	psi-mi:“MI:0915”(physical association)	0.870
RBM17	GOLGA2	psi-mi:“MI:0915”(physical association)	0.830
GOLGA2	RBM17	psi-mi:“MI:0915”(physical association)	0.830
CEP55	RBM17	psi-mi:“MI:0915”(physical association)	0.780
RBM17	CEP55	psi-mi:“MI:0915”(physical association)	0.780
RBM17	U2SURP	psi-mi:“MI:0914”(association)	0.740
RBM17	SF1	psi-mi:“MI:0407”(direct interaction)	0.730
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730

BioGRID (321): RBM17 (Two-hybrid), RBM17 (Two-hybrid), RBM17 (Two-hybrid), RBM17 (Two-hybrid), RBM17 (Two-hybrid), RBM17 (Two-hybrid), RBM17 (Two-hybrid), RBM17 (Two-hybrid), FAM9B (Two-hybrid), RBM17 (Affinity Capture-MS), RBM17 (Affinity Capture-MS), RBM17 (Two-hybrid), RBM17 (Affinity Capture-MS), SON (Co-fractionation), RBM17 (Two-hybrid)

ESM2 similar proteins: A0JM64, A0JMV4, A2VDN6, A4IFB1, A4IGK4, D3ZTQ1, O70523, O75400, P35922, P51113, P51114, P51115, P70501, P98175, Q06787, Q12872, Q15459, Q2KHP9, Q2KIA6, Q2NLB0, Q2TBT7, Q3TCX3, Q3USH5, Q5BJ56, Q5R539, Q5R9B4, Q5SFM8, Q5T8P6, Q5XI81, Q61584, Q66I22, Q6DDU9, Q6GLC9, Q6NZ18, Q6NZN0, Q7TN31, Q80TJ7, Q80WE1, Q8CGC4, Q8JZX4

Diamond homologs: A1A4K8, A1A5R1, A6NDE4, A6NEQ0, A6NFN3, A6QPR6, B0BNE4, O13845, O14369, O43251, O89086, P04147, P0C7P1, P0CB38, P0DJD3, P0DJD4, P19339, P41891, P42696, P57052, P60047, P60048, P60049, P60050, P60824, P60825, P60826, P62995, P62996, P62997, P98179, Q01081, Q03251, Q03878, Q06106, Q09511, Q10572, Q14011, Q14498, Q15415

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
CDK11B	“up-regulates activity”	RBM17	phosphorylation
CLK1	“up-regulates activity”	RBM17	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 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
mRNA Splicing - Minor Pathway	8	18.5×	6e-07
mRNA Polyadenylation	20	18.1×	1e-17
mRNA Splicing	16	18.1×	3e-14
Processing of Capped Intron-Containing Pre-mRNA	19	16.1×	7e-16
mRNA Splicing - Major Pathway	25	14.1×	1e-19
SARS-CoV-2 modulates host translation machinery	6	13.8×	3e-04
RNA Polymerase II Transcription Termination	6	13.6×	3e-04
snRNP Assembly	6	13.1×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	9	43.5×	1e-10
spliceosomal complex assembly	9	42.0×	1e-10
positive regulation of transcription by RNA polymerase III	5	36.3×	3e-05
spliceosomal snRNP assembly	5	22.5×	3e-04
mRNA splicing, via spliceosome	20	14.2×	9e-15
negative regulation of translation	9	13.7×	3e-06
mRNA transport	6	12.2×	1e-03
endoplasmic reticulum unfolded protein response	5	11.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1927 predictions. Top by Δscore:

Variant	Effect	Δscore
10:6097044:TCAGC:T	acceptor_loss	1.0000
10:6097046:A:AC	acceptor_loss	1.0000
10:6097046:A:AG	acceptor_gain	1.0000
10:6097047:G:A	acceptor_loss	1.0000
10:6097047:G:GA	acceptor_gain	1.0000
10:6097047:GC:G	acceptor_gain	1.0000
10:6097047:GCA:G	acceptor_gain	1.0000
10:6097047:GCAT:G	acceptor_gain	1.0000
10:6097047:GCATT:G	acceptor_gain	1.0000
10:6101259:T:TA	acceptor_gain	1.0000
10:6101262:T:A	acceptor_gain	1.0000
10:6101262:T:TA	acceptor_loss	1.0000
10:6101266:TTTA:T	acceptor_loss	1.0000
10:6101269:A:AG	acceptor_gain	1.0000
10:6101269:A:C	acceptor_loss	1.0000
10:6101270:G:GT	acceptor_gain	1.0000
10:6101270:GA:G	acceptor_gain	1.0000
10:6101270:GAGC:G	acceptor_gain	1.0000
10:6101270:GAGCC:G	acceptor_gain	1.0000
10:6101384:GAAG:G	donor_gain	1.0000
10:6101389:T:G	donor_loss	1.0000
10:6104926:CTCA:C	acceptor_loss	1.0000
10:6104927:TCAG:T	acceptor_loss	1.0000
10:6104928:CA:C	acceptor_loss	1.0000
10:6104929:A:AG	acceptor_gain	1.0000
10:6104929:AG:A	acceptor_gain	1.0000
10:6104930:G:GG	acceptor_gain	1.0000
10:6104930:GG:G	acceptor_gain	1.0000
10:6105078:G:GT	donor_gain	1.0000
10:6105079:A:T	donor_gain	1.0000

AlphaMissense

2615 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:6097120:T:A	W19R	1.000
10:6097120:T:C	W19R	1.000
10:6097122:G:C	W19C	1.000
10:6097122:G:T	W19C	1.000
10:6097139:T:C	L25P	1.000
10:6097142:T:C	L26P	1.000
10:6097154:T:C	L30P	1.000
10:6101308:T:A	V54D	1.000
10:6104988:T:C	Y100H	1.000
10:6104989:A:G	Y100C	1.000
10:6108707:C:A	A176D	1.000
10:6112218:T:A	V238E	1.000
10:6112220:G:A	A239T	1.000
10:6112221:C:A	A239E	1.000
10:6112221:C:T	A239V	1.000
10:6112230:T:A	I242N	1.000
10:6112230:T:C	I242T	1.000
10:6112230:T:G	I242S	1.000
10:6112232:A:G	M243V	1.000
10:6112233:T:A	M243K	1.000
10:6112233:T:C	M243T	1.000
10:6112233:T:G	M243R	1.000
10:6112234:G:A	M243I	1.000
10:6112234:G:C	M243I	1.000
10:6112234:G:T	M243I	1.000
10:6112236:A:C	Q244P	1.000
10:6112238:A:G	K245E	1.000
10:6112240:G:C	K245N	1.000
10:6112240:G:T	K245N	1.000
10:6112241:T:G	Y246D	1.000

dbSNP variants (sampled 300 via entrez): RS1000003340 (10:6117826 A>G), RS1000013966 (10:6094311 TTGC>T), RS1000085658 (10:6094520 T>G), RS1000097710 (10:6106340 T>A,C), RS1000245806 (10:6091064 T>C), RS1000344395 (10:6111924 G>A,C), RS1000401042 (10:6106301 G>A), RS1000412550 (10:6105944 T>C), RS1000499392 (10:6117206 A>G), RS1000547012 (10:6116915 G>A), RS1000608699 (10:6110205 G>A), RS1000736744 (10:6104556 ATTTTT>A,ATT,ATTTTTT), RS1000742794 (10:6107458 A>C,G,T), RS1000811836 (10:6090894 T>A), RS1000865210 (10:6089183 G>A,T)

Disease associations

OMIM: gene MIM:606935 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000662_10	Vitiligo	3.000000e-09
GCST002322_15	Asthma and hay fever	5.000000e-07
GCST002875_32	Diisocyanate-induced asthma	2.000000e-06
GCST003088_6	Soluble interleukin-2 receptor subunit alpha	3.000000e-09
GCST003088_7	Soluble interleukin-2 receptor subunit alpha	4.000000e-10
GCST004132_31	Crohn’s disease	2.000000e-08
GCST005531_100	Multiple sclerosis	9.000000e-06
GCST007563_28	Allergic disease (asthma, hay fever or eczema)	4.000000e-12
GCST007564_22	Asthma or allergic disease (pleiotropy)	2.000000e-11
GCST007678_3	Brooding (response to stress)	3.000000e-06
GCST008916_1	Asthma	6.000000e-17
GCST008916_122	Asthma	4.000000e-08
GCST009798_3	Asthma	1.000000e-17

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0007650	soluble interleukin-2 receptor subunit alpha measurement
EFO:0009858	brooding stress response

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4680038 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

11 potent at pChembl≥5 of 13 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.41	Kd	38.52	nM	CHEMBL5653589
7.25	ED50	55.92	nM	CHEMBL5653589
6.75	Kd	180	nM	CHEMBL4747647
6.58	IC50	260	nM	MOLIBRESIB
6.29	Kd	510	nM	CHEMBL4797754
6.12	Kd	750	nM	CHEMBL4786448
6.10	Kd	800	nM	CHEMBL4788784
6.02	Kd	960	nM	CHEMBL4799705
5.90	Kd	1260	nM	CHEMBL4791647
5.85	Kd	1400	nM	CHEMBL4743783
5.73	Kd	1850	nM	CHEMBL4794936

PubChem BioAssay actives

10 with measured affinity, of 21 total; 10 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	2149204: Binding affinity to human RBM17 incubated for 45 mins by Kinobead based pull down assay	kd	0.0385	uM
(2S)-6-amino-2-[[(2S,5S,8S,11S,14R,23R)-23-amino-11-(carboxymethyl)-5-[3-(diaminomethylideneamino)propyl]-2-(hydroxymethyl)-8-(1H-indol-3-ylmethyl)-3,6,9,12,17,24-hexaoxo-1,4,7,10,13,18-hexazacyclotetracosane-14-carbonyl]amino]hexanoic acid	1679191: Binding affinity to His-Z-tagged SPF45 (unknown origin) UHM domain expressed in Escherichia coli BL21 (DE3) cells by ITC analysis	kd	0.1800	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178488: Inhibition of RBM17 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.2600	uM
(2S)-2-[[(2S,5S,8S,11S,14R,23R)-23-amino-11-(carboxymethyl)-5-[3-(diaminomethylideneamino)propyl]-2-(hydroxymethyl)-8-(1H-indol-3-ylmethyl)-3,6,9,12,17,24-hexaoxo-1,4,7,10,13,18-hexazacyclotetracosane-14-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1679191: Binding affinity to His-Z-tagged SPF45 (unknown origin) UHM domain expressed in Escherichia coli BL21 (DE3) cells by ITC analysis	kd	0.5100	uM
2-[[(2S,5S,8S,11S,14R,23R)-23-amino-11-(carboxymethyl)-5-[3-(diaminomethylideneamino)propyl]-2-(hydroxymethyl)-8-(1H-indol-3-ylmethyl)-3,6,9,12,17,24-hexaoxo-1,4,7,10,13,18-hexazacyclotetracosane-14-carbonyl]amino]-6-(diaminomethylideneamino)hexanoic acid	1679191: Binding affinity to His-Z-tagged SPF45 (unknown origin) UHM domain expressed in Escherichia coli BL21 (DE3) cells by ITC analysis	kd	0.7500	uM
(2S)-2-[[(2S,5S,8S,11S,14R,23R)-23-amino-11-(carboxymethyl)-5-[3-(diaminomethylideneamino)propyl]-2-(hydroxymethyl)-8-(1H-indol-3-ylmethyl)-3,6,9,12,17,24-hexaoxo-1,4,7,10,13,18-hexazacyclotetracosane-14-carbonyl]amino]-3-(1H-indol-3-yl)propanoic acid	1679191: Binding affinity to His-Z-tagged SPF45 (unknown origin) UHM domain expressed in Escherichia coli BL21 (DE3) cells by ITC analysis	kd	0.8000	uM
(2S)-2-[[(2S,5S,8S,11S,14R,23R)-23-amino-11-(carboxymethyl)-5-[3-(diaminomethylideneamino)propyl]-2-(hydroxymethyl)-8-(1H-indol-3-ylmethyl)-3,6,9,12,17,24-hexaoxo-1,4,7,10,13,18-hexazacyclotetracosane-14-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoic acid	1679191: Binding affinity to His-Z-tagged SPF45 (unknown origin) UHM domain expressed in Escherichia coli BL21 (DE3) cells by ITC analysis	kd	0.9600	uM
(2S)-6-amino-2-[[(2S,5S,8S,11S,14R,23R)-23-amino-11-(carboxymethyl)-5-[3-(diaminomethylideneamino)propyl]-2-(hydroxymethyl)-8-(1H-indol-3-ylmethyl)-18-methyl-3,6,9,12,17,24-hexaoxo-1,4,7,10,13,18-hexazacyclotetracosane-14-carbonyl]amino]hexanoic acid	1679191: Binding affinity to His-Z-tagged SPF45 (unknown origin) UHM domain expressed in Escherichia coli BL21 (DE3) cells by ITC analysis	kd	1.2600	uM
(2S,5S,8S,11S,14R,23R)-23-amino-11-(carboxymethyl)-5-[3-(diaminomethylideneamino)propyl]-2-(hydroxymethyl)-8-(1H-indol-3-ylmethyl)-3,6,9,12,17,24-hexaoxo-1,4,7,10,13,18-hexazacyclotetracosane-14-carboxylic acid	1679191: Binding affinity to His-Z-tagged SPF45 (unknown origin) UHM domain expressed in Escherichia coli BL21 (DE3) cells by ITC analysis	kd	1.4000	uM
(2S)-2-[[(2S,5S,8S,11S,14R,23R)-23-amino-11-(carboxymethyl)-5-[3-(diaminomethylideneamino)propyl]-2-(hydroxymethyl)-8-(1H-indol-3-ylmethyl)-3,6,9,12,17,24-hexaoxo-1,4,7,10,13,18-hexazacyclotetracosane-14-carbonyl]amino]-3-(4-hydroxyphenyl)propanoic acid	1679191: Binding affinity to His-Z-tagged SPF45 (unknown origin) UHM domain expressed in Escherichia coli BL21 (DE3) cells by ITC analysis	kd	1.8500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
nickel sulfate	decreases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	2
Doxorubicin	decreases expression, decreases response to substance	2
Valproic Acid	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
bisphenol A	affects cotreatment, increases expression	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
LY 117018	decreases reaction, decreases response to substance	1
coumarin	decreases phosphorylation	1
nivalenol	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	decreases expression	1
Pemetrexed	decreases response to substance	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Vinorelbine	decreases response to substance	1
Arsenic Trioxide	increases expression	1
Gemcitabine	decreases response to substance	1
Caffeine	affects phosphorylation	1
Cannabidiol	decreases expression	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Dinitrochlorobenzene	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Etoposide	decreases response to substance	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4673838	Binding	Inhibition of SPF45-mediated splicing in human HeLa nuclear extracts assessed as reduction in complex A formation during spliceosome-assembly at 25 to 500 uM incubated for 20 mins before addition of IgM pre-mRNA as the splicing substrate by	Rational Design of Cyclic Peptide Inhibitors of U2AF Homology Motif (UHM) Domains To Modulate Pre-mRNA Splicing. — J Med Chem

Clinical trials (associated diseases)

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