IWS1

Summary

IWS1 (interacts with SUPT6H, CTD assembly factor 1, HGNC:25467) is a protein-coding gene on chromosome 2q14.3, encoding Protein IWS1 homolog (Q96ST2). Transcription factor which plays a key role in defining the composition of the RNA polymerase II (RNAPII) elongation complex and in modulating the production of mature mRNA transcripts.

Involved in regulation of mRNA export from nucleus; regulation of mRNA processing; and transcription elongation-coupled chromatin remodeling. Located in nucleoplasm.

Source: NCBI Gene 55677 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 117 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_017969

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25467
Approved symbol	IWS1
Name	interacts with SUPT6H, CTD assembly factor 1
Location	2q14.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761G0123, FLJ10006, FLJ14655, FLJ32319
Ensembl gene	ENSG00000163166
Ensembl biotype	protein_coding
Entrez	55677

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding_CDS_not_defined, 6 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000295321, ENST00000409725, ENST00000412979, ENST00000436740, ENST00000460511, ENST00000478949, ENST00000479083, ENST00000483889, ENST00000486662, ENST00000495369, ENST00000497888, ENST00000637187, ENST00000866713, ENST00000922529, ENST00000953050

RefSeq mRNA: 2 — MANE Select: NM_017969 NM_001410923, NM_017969

CCDS: CCDS2146, CCDS92859

Canonical transcript exons

ENST00000295321 — 14 exons

Exon	Start	End
ENSE00001137008	127486553	127486664
ENSE00001137018	127489179	127489235
ENSE00001137028	127489832	127489943
ENSE00001137038	127491971	127492088
ENSE00001904167	127526175	127526489
ENSE00001924647	127480812	127481175
ENSE00003792313	127493281	127493410
ENSE00003990049	127498140	127498237
ENSE00003990051	127503387	127503576
ENSE00003990052	127504684	127505752
ENSE00003990053	127523676	127523791
ENSE00003990054	127495998	127496148
ENSE00003990055	127502815	127502872
ENSE00003990056	127494872	127494954

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 96.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.3722 / max 705.5640, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30533	25.3728	1817
30532	1.2211	768
30529	0.5340	76
30531	0.1762	53
30530	0.0681	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	96.40	gold quality
ileal mucosa	UBERON:0000331	95.92	gold quality
calcaneal tendon	UBERON:0003701	95.66	gold quality
tendon of biceps brachii	UBERON:0008188	95.39	gold quality
gastrocnemius	UBERON:0001388	95.27	gold quality
muscle of leg	UBERON:0001383	94.93	gold quality
tendon	UBERON:0000043	94.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.33	gold quality
right atrium auricular region	UBERON:0006631	94.06	gold quality
cardiac atrium	UBERON:0002081	93.78	gold quality
sural nerve	UBERON:0015488	93.70	gold quality
muscle organ	UBERON:0001630	93.42	gold quality
heart left ventricle	UBERON:0002084	93.37	gold quality
apex of heart	UBERON:0002098	93.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.36	gold quality
oocyte	CL:0000023	93.16	gold quality
cardiac ventricle	UBERON:0002082	93.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.82	gold quality
corpus callosum	UBERON:0002336	92.80	gold quality
ganglionic eminence	UBERON:0004023	92.64	gold quality
embryo	UBERON:0000922	92.63	gold quality
cortical plate	UBERON:0005343	92.62	gold quality
heart	UBERON:0000948	92.60	gold quality
ventricular zone	UBERON:0003053	92.58	gold quality
right lobe of liver	UBERON:0001114	92.35	gold quality
spinal cord	UBERON:0002240	92.28	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.22	silver quality
upper arm skin	UBERON:0004263	92.13	gold quality
adenohypophysis	UBERON:0002196	92.10	gold quality
mucosa of transverse colon	UBERON:0004991	91.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting IWS1, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-629-3P	99.85	67.99	1875
HSA-LET-7G-3P	99.85	70.43	1929
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-4307	99.82	70.45	3374
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-410-3P	99.27	69.98	2457

Literature-anchored findings (GeneRIF, showing 7)

• Here we report that the human homolog of Iws1, hIws1, physically interacts with protein arginine methyltransferases PRMT5 which methylates elongation factor Spt5 and regulates its interaction with RNA polymerase II. (PMID:17184735)
• binding of Spt6 to Ser2-P RNAPII provides a cotranscriptional mechanism to recruit Iws1, REF1/Aly, and associated mRNA processing, surveillance, and export factors to responsive genes. (PMID:17234882)
• recombinant Spt6 binds selectively to a stretch of uninterrupted consensus repeats located in the N-terminal half of the CTD and recruits Iws1 (PMID:19141475)
• IWS1, an RNA processing regulator, is phosphorylated by Akt3 and Akt1 at Ser720/Thr721 in lung cancer (PMID:24462114)
• Altogether, these results indicate that a complex containing LEDGF/p75, Iws1, and Spt6 participates in regulating postintegration steps of HIV latency. (PMID:25590759)
• common LEDGF/p75 interaction interface shared by JPO2, PogZ, MLL1, IWS1 and HIV IN (PMID:26245978)
• A ubiquitous disordered protein interaction module orchestrates transcription elongation. (PMID:34822292)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000087950
mus_musculus	Iws1	ENSMUSG00000024384
rattus_norvegicus	Iws1	ENSRNOG00000014630
drosophila_melanogaster	Cp190	FBGN0000283
drosophila_melanogaster	CG9915	FBGN0030738
drosophila_melanogaster	CG12592	FBGN0037811
caenorhabditis_elegans		WBGENE00008729

Paralogs (3): SAMD15 (ENSG00000100583), MDN1 (ENSG00000112159), TCHHL1 (ENSG00000182898)

Protein

Protein identifiers

Protein IWS1 homolog — Q96ST2 (reviewed: Q96ST2)

Alternative names: IWS1-like protein

All UniProt accessions (4): Q96ST2, A0A1B0GW95, B8ZZB6, H7C0U1

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor which plays a key role in defining the composition of the RNA polymerase II (RNAPII) elongation complex and in modulating the production of mature mRNA transcripts. Acts as an assembly factor to recruit various factors to the RNAPII elongation complex and is recruited to the complex via binding to the transcription elongation factor SUPT6H bound to the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2) to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription.

Subunit / interactions. Interacts with SUPT6H; binds preferentially to the POLR2A-bound SUPT6H. Interacts with ALYREF/THOC4, SETD2 and PRMT5. Interacts with HDGFRP2. Interacts (via IBM motif) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylation increases its interaction with PSIP1.

Similarity. Belongs to the IWS1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96ST2-1	1	yes
Q96ST2-2	2
Q96ST2-3	3

RefSeq proteins (2): NP_001397852, NP_060439* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017923	TFIIS_N	Domain
IPR035441	TFIIS/LEDGF_dom_sf	Homologous_superfamily
IPR051037	RNAPII_TF_IWS1	Family

Pfam: PF08711

UniProt features (97 total): modified residue 49, helix 15, compositionally biased region 11, region of interest 4, sequence conflict 4, repeat 3, mutagenesis site 3, splice variant 2, sequence variant 2, chain 1, domain 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
9MLC	ELECTRON MICROSCOPY	2.4
9EGX	ELECTRON MICROSCOPY	2.9
9EGY	ELECTRON MICROSCOPY	2.9
9EGZ	ELECTRON MICROSCOPY	2.9
9EH1	ELECTRON MICROSCOPY	3.1
9EH2	ELECTRON MICROSCOPY	3.1
9EH0	ELECTRON MICROSCOPY	3.6
9RTT	ELECTRON MICROSCOPY	4.01
6EMR	SOLUTION NMR
6ZV1	SOLUTION NMR
6ZV4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96ST2-F1	54.89	0.13

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 (49): 1, 27, 54, 69, 157, 159, 183, 196, 198, 209, 235, 237, 248, 250, 261, 263, 274, 276, 287, 289 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
476	loss of interaction with psip1; when associated with a-477.
477	loss of interaction with psip1; when associated with a-476.
480	phosphomimetic mutant. moderate increase in interaction with psip1.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 121 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, PAX4_01, GOBP_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_NUCLEAR_TRANSPORT, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_REGULATION_OF_NUCLEOCYTOPLASMIC_TRANSPORT, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, YY1_02, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_RNA_SPLICING, CREB_Q3, GOBP_EMBRYO_DEVELOPMENT, EGR1_01

GO Biological Process (9): in utero embryonic development (GO:0001701), chromatin remodeling (GO:0006338), mRNA processing (GO:0006397), RNA splicing (GO:0008380), regulation of mRNA export from nucleus (GO:0010793), poly(A)+ mRNA export from nucleus (GO:0016973), regulation of mRNA processing (GO:0050684), transcription elongation-coupled chromatin remodeling (GO:0140673), mRNA transport (GO:0051028)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RNA Polymerase II Transcription	2
RNA Polymerase II Transcription Elongation	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
mRNA export from nucleus	2
chordate embryonic development	1
chromatin organization	1
mRNA metabolic process	1
regulation of RNA export from nucleus	1
regulation of ribonucleoprotein complex localization	1
mRNA processing	1
regulation of mRNA metabolic process	1
chromatin remodeling	1
transcription elongation by RNA polymerase II	1
RNA transport	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2106 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IWS1	SUPT6H	Q7KZ85	997
IWS1	SETD2	Q9BYW2	865
IWS1	TCEA1	P23193	705
IWS1	TCEA2	Q15560	703
IWS1	SUPT4H1	P63272	692
IWS1	TCEA3	O75764	687
IWS1	SUPT5H	O00267	648
IWS1	JAG2	Q9Y219	587
IWS1	ALYREF	Q86V81	574
IWS1	LEO1	Q8WVC0	571
IWS1	PSIP1	O75475	567
IWS1	PCF11	O94913	566
IWS1	CDCA7L	Q96GN5	544
IWS1	CCNT2	O60583	536
IWS1	CDK9	P50750	518

IntAct

53 interactions, top by confidence:

A	B	Type	Score
IWS1	SUPT5H	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
IWS1	XRN2	psi-mi:“MI:0915”(physical association)	0.400
STAT2	IWS1	psi-mi:“MI:0915”(physical association)	0.370
Rprd1b	POLR2B	psi-mi:“MI:0914”(association)	0.350
DDX41	DDX39A	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
E6	TRAFD1	psi-mi:“MI:0914”(association)	0.350
BFRF1A	SHTN1	psi-mi:“MI:0914”(association)	0.350
MAB21L2	PTBP1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
HMGB1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
WDR48	UNC13B	psi-mi:“MI:0914”(association)	0.350
	HTATSF1	psi-mi:“MI:0914”(association)	0.350
PPM1A	BCKDK	psi-mi:“MI:0914”(association)	0.350
	SDCBP	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HMGA1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
SNRPA	DDX39A	psi-mi:“MI:0914”(association)	0.350
SNRPC	DDX39A	psi-mi:“MI:0914”(association)	0.350
SNRPF	SUPT5H	psi-mi:“MI:0914”(association)	0.350
SRP9	RPS3A	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
TOP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
TOP2A	RPL6	psi-mi:“MI:0914”(association)	0.350
HDGFL2	CIBAR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (141): ERICH2 (Two-hybrid), KRTAP10-3 (Two-hybrid), IWS1 (Affinity Capture-RNA), IWS1 (Affinity Capture-RNA), IWS1 (Affinity Capture-RNA), IWS1 (Affinity Capture-RNA), CTR9 (Co-fractionation), IWS1 (Co-fractionation), IWS1 (Proximity Label-MS), IWS1 (Affinity Capture-MS), PRCC (Affinity Capture-MS), SUPT5H (Affinity Capture-MS), CTDP1 (Affinity Capture-MS), RNF40 (Affinity Capture-MS), ACTR1A (Affinity Capture-MS)

ESM2 similar proteins: A0JP43, A1L162, A2VCV0, A5PK42, B4R4H1, F4HTH8, F4KIA8, F6QRE9, F8VPQ2, I1HNB2, O43719, P29374, P48785, P79149, Q07G43, Q13342, Q15361, Q28EG9, Q3SWT4, Q5H9L4, Q5R675, Q5RB63, Q5RF97, Q5T3I0, Q61584, Q62187, Q66HD8, Q6NRI5, Q6NVE8, Q6NYJ3, Q6PG04, Q794H2, Q7T293, Q8BGC0, Q8C1D8, Q8C627, Q8N4S0, Q8NEP3, Q8RXT5, Q924R9

Diamond homologs: O42964, O49413, P0CO38, P0CO39, Q06505, Q19375, Q3SWT4, Q4IJ11, Q4P7X6, Q4WSM6, Q505H7, Q5AAR0, Q5BEG5, Q61MR2, Q6BQ49, Q6CGB2, Q6CVL1, Q6DE96, Q6FVX3, Q75EH2, Q870S2, Q8C1D8, Q96ST2, F4ICK8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
AKT3	“up-regulates activity”	IWS1	phosphorylation
IWS1	“form complex”	“Iws1:Spt6:CTD complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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 Polyadenylation	11	20.1×	1e-09
Inhibition of DNA recombination at telomere	5	17.5×	3e-04
Transcriptional regulation by small RNAs	5	15.1×	4e-04
mRNA Splicing	6	13.7×	3e-04
Processing of Capped Intron-Containing Pre-mRNA	8	13.7×	9e-06
mRNA Splicing - Major Pathway	12	13.7×	7e-09
CHD1 and CHD2 subfamily	6	13.6×	3e-04
B-WICH complex positively regulates rRNA expression	5	12.7×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	7	16.4×	7e-05
mRNA splicing, via spliceosome	8	12.2×	7e-05
chromatin remodeling	7	8.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	82
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1340017	GRCh37/hg19 2q13-22.3(chr2:111484468-146333604)x3	Pathogenic

SpliceAI

3025 predictions. Top by Δscore:

Variant	Effect	Δscore
2:127489177:A:AC	donor_gain	1.0000
2:127489178:C:CT	donor_gain	1.0000
2:127489178:CTT:C	donor_gain	1.0000
2:127489178:CTTCT:C	donor_gain	1.0000
2:127489180:T:TA	donor_gain	1.0000
2:127489187:T:A	donor_gain	1.0000
2:127489231:CAGTG:C	acceptor_gain	1.0000
2:127489232:AGTG:A	acceptor_gain	1.0000
2:127489233:GTG:G	acceptor_gain	1.0000
2:127489234:TG:T	acceptor_gain	1.0000
2:127489235:GC:G	acceptor_loss	1.0000
2:127489236:C:CC	acceptor_gain	1.0000
2:127489237:T:A	acceptor_loss	1.0000
2:127489827:CATA:C	donor_loss	1.0000
2:127489828:ATACC:A	donor_loss	1.0000
2:127489829:TAC:T	donor_loss	1.0000
2:127489830:A:T	donor_loss	1.0000
2:127489831:CCTGT:C	donor_loss	1.0000
2:127489939:CTCAT:C	acceptor_gain	1.0000
2:127489940:TCAT:T	acceptor_gain	1.0000
2:127489941:CAT:C	acceptor_gain	1.0000
2:127489941:CATC:C	acceptor_gain	1.0000
2:127489942:AT:A	acceptor_gain	1.0000
2:127489942:ATCT:A	acceptor_loss	1.0000
2:127489943:TC:T	acceptor_loss	1.0000
2:127489944:C:CC	acceptor_gain	1.0000
2:127489944:C:CG	acceptor_loss	1.0000
2:127491966:CATA:C	donor_gain	1.0000
2:127491967:ATACT:A	donor_loss	1.0000
2:127491968:TACTG:T	donor_loss	1.0000

AlphaMissense

5554 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:127481054:A:G	M817T	1.000
2:127481063:C:A	G814V	1.000
2:127481063:C:T	G814D	1.000
2:127481064:C:A	G814C	1.000
2:127481064:C:G	G814R	1.000
2:127486579:A:G	W768R	1.000
2:127486579:A:T	W768R	1.000
2:127486584:G:C	P766R	1.000
2:127486584:G:T	P766H	1.000
2:127486585:G:A	P766S	1.000
2:127486585:G:T	P766T	1.000
2:127486586:C:A	R765S	1.000
2:127486586:C:G	R765S	1.000
2:127486587:C:A	R765M	1.000
2:127486587:C:G	R765T	1.000
2:127486588:T:C	R765G	1.000
2:127486593:A:T	V763D	1.000
2:127486596:T:C	Y762C	1.000
2:127486596:T:G	Y762S	1.000
2:127486597:A:C	Y762D	1.000
2:127486597:A:G	Y762H	1.000
2:127486597:A:T	Y762N	1.000
2:127486600:C:G	D761H	1.000
2:127486617:G:C	P755R	1.000
2:127486617:G:T	P755Q	1.000
2:127486618:G:A	P755S	1.000
2:127486618:G:T	P755T	1.000
2:127486620:A:T	V754D	1.000
2:127486622:C:A	R753S	1.000
2:127486622:C:G	R753S	1.000

dbSNP variants (sampled 300 via entrez): RS1000044134 (2:127494573 G>A,C), RS1000071030 (2:127508945 T>C), RS1000150372 (2:127526980 A>G,T), RS1000275938 (2:127502389 T>C), RS1000318920 (2:127515429 C>A), RS1000369851 (2:127488438 C>T), RS1000370791 (2:127490015 C>T), RS1000429195 (2:127496624 T>A), RS1000490006 (2:127482236 G>A), RS1000491298 (2:127523247 C>T), RS1000567399 (2:127502655 G>A), RS1000585568 (2:127517740 G>A), RS1000647176 (2:127512022 T>C), RS1000706065 (2:127484304 A>C,G,T), RS1000741536 (2:127511797 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008309_10	Cardiac troponin-I levels	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010071	cardiac troponin I measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724649 (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

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
7.22	IC50	60	nM	MOLIBRESIB
6.59	Kd	259	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178990: Inhibition of IWS1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
methylparaben	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
Resveratrol	increases expression, affects cotreatment	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Cannabidiol	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Hydrogen Peroxide	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697720	Binding	Inhibition of IWS1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1UY	Abcam HeLa IWS1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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