CTDSP1

Summary

CTDSP1 (CTD small phosphatase 1, HGNC:21614) is a protein-coding gene on chromosome 2q35, encoding Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (Q9GZU7). Preferentially catalyzes the dephosphorylation of ‘Ser-5’ within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A.

This gene encodes a member of the small C-terminal domain phosphatase (SCP) family of nuclear phosphatases. These proteins play a role in transcriptional regulation through specific dephosphorylation of phosphoserine 5 within tandem heptapeptide repeats of the C-terminal domain of RNA polymerase II. The encoded protein plays a role in neuronal gene silencing in non-neuronal cells, and may also inhibit osteoblast differentiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 58190 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 51 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21614
Approved symbol	CTDSP1
Name	CTD small phosphatase 1
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	NLIIF, SCP1
Ensembl gene	ENSG00000144579
Ensembl biotype	protein_coding
OMIM	605323
Entrez	58190

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000273062, ENST00000428361, ENST00000431127, ENST00000443891, ENST00000452977, ENST00000464255, ENST00000473420, ENST00000482272, ENST00000488627, ENST00000491064, ENST00000492545, ENST00000494067, ENST00000496785, ENST00000497677, ENST00000498160, ENST00000710828, ENST00000710837, ENST00000710838, ENST00000710839, ENST00000885504, ENST00000885505

RefSeq mRNA: 12 — MANE Select: NM_021198 NM_001206878, NM_001400268, NM_001400269, NM_001400270, NM_001400271, NM_001400272, NM_001400273, NM_001400274, NM_001400275, NM_001400276, NM_021198, NM_182642

CCDS: CCDS2416

Canonical transcript exons

ENST00000273062 — 7 exons

Exon	Start	End
ENSE00001038975	218399868	218400157
ENSE00001930491	218404297	218405941
ENSE00003585758	218403232	218403417
ENSE00004013738	218402111	218402215
ENSE00004013776	218402349	218402405
ENSE00004013779	218401564	218401712
ENSE00004013784	218403035	218403127

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.6429 / max 281.7028, expressed in 1820 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25340	24.2154	1801
25338	6.2869	1669
25341	4.0097	1566
25342	2.8629	1280
25343	2.6175	1246
25335	1.7874	452
25339	1.3546	839
25336	0.3232	171
25337	0.1853	95

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.74	gold quality
mucosa of stomach	UBERON:0001199	98.10	gold quality
right coronary artery	UBERON:0001625	98.10	gold quality
body of stomach	UBERON:0001161	97.90	gold quality
descending thoracic aorta	UBERON:0002345	97.87	gold quality
apex of heart	UBERON:0002098	97.84	gold quality
left uterine tube	UBERON:0001303	97.82	gold quality
right ovary	UBERON:0002118	97.76	gold quality
thoracic aorta	UBERON:0001515	97.75	gold quality
endocervix	UBERON:0000458	97.74	gold quality
popliteal artery	UBERON:0002250	97.72	gold quality
tibial artery	UBERON:0007610	97.72	gold quality
right lobe of thyroid gland	UBERON:0001119	97.71	gold quality
ascending aorta	UBERON:0001496	97.70	gold quality
aorta	UBERON:0000947	97.67	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.67	gold quality
right lung	UBERON:0002167	97.65	gold quality
metanephros cortex	UBERON:0010533	97.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.60	gold quality
body of uterus	UBERON:0009853	97.59	gold quality
lower esophagus	UBERON:0013473	97.59	gold quality
left coronary artery	UBERON:0001626	97.51	gold quality
left ovary	UBERON:0002119	97.49	gold quality
left lobe of thyroid gland	UBERON:0001120	97.35	gold quality
tibial nerve	UBERON:0001323	97.34	gold quality
monocyte	CL:0000576	97.30	gold quality
coronary artery	UBERON:0001621	97.30	gold quality
leukocyte	CL:0000738	97.26	gold quality
stomach	UBERON:0000945	97.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

119 targeting CTDSP1, 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-6798-5P	100.00	65.77	699
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718

Literature-anchored findings (GeneRIF, showing 16)

• Polymorphisms vary significantly between races; Not associated with TB susceptibility in Caucasians. (PMID:11950066)
• SCP1 may play a role in the regulation of gene expression, possibly by controlling the transition from initiation/capping to processive transcript elongation (PMID:12721286)
• results show that REST/NRSF recruits SCPs to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells (PMID:15681389)
• SCP1 acts as a phosphatase for regulatory phosphorylations in the linker region of Smad1 and Smad2. (PMID:17085434)
• Captured the phosphoryl-aspartate intermediate in the crystal structure of a Scp1D206A mutant soaked with para-nitrophenyl phosphate (pNPP), providing strong evidence for the proposed mechanism. (PMID:20222012)
• SCP1 phosphatase substrate specificity: CdcA3 could be an enzymatic substrate for SCP1. (PMID:24769477)
• hSCP1 may be an beta-O-linked N-acetylglucosamine modified protein in vivo. (PMID:25081999)
• CTDSP1 activity stabilizes REST in stem cells and ERK-dependent phosphorylation combined with Pin1 activity promotes REST degradation in neural progenitors. (PMID:25197063)
• SCP1 regulates c-Myc stability and functions through dephosphorylating c-Myc Serine-62. (PMID:25893300)
• SCP1 is the phosphatase that counterregulates the MAPK-mediated phosphorylation of Ser(68)-Twist1. (PMID:26975371)
• Our results provide a novel mechanistic insight into the activation of Myc by 27-HC via transcriptional repression of PP2A, SCP1 and FBW7 to increase Myc protein stability in breast cancer cells. (PMID:27751849)
• REST is a bona fide substrate for SCP1 in vivo and that SCP1 phosphatase activity protects REST against degradation. (PMID:30217818)
• Tumor suppressor properties of the small C-terminal domain phosphatases in non-small cell lung cancer. (PMID:31774910)
• Deubiquitinase USP29 promotes gastric cancer cell migration by cooperating with phosphatase SCP1 to stabilize Snail protein. (PMID:32973332)
• GPC5 suppresses lung cancer progression and metastasis via intracellular CTDSP1/AhR/ARNT signaling axis and extracellular exosome secretion. (PMID:34079082)
• C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration in peripheral nerve tissue. (PMID:34262056)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctdsp1	ENSDARG00000040674
mus_musculus	Ctdsp1	ENSMUSG00000026176
rattus_norvegicus	Ctdsp1	ENSRNOG00000015295
drosophila_melanogaster	hzg	FBGN0036556
caenorhabditis_elegans	scpl-1	WBGENE00007054

Paralogs (5): TIMM50 (ENSG00000105197), CTDSPL2 (ENSG00000137770), CTDSPL (ENSG00000144677), CTDSP2 (ENSG00000175215), CTDNEP1 (ENSG00000175826)

Protein

Protein identifiers

Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 — Q9GZU7 (reviewed: Q9GZU7)

Alternative names: Nuclear LIM interactor-interacting factor 3, Small C-terminal domain phosphatase 1

All UniProt accessions (4): Q9GZU7, A0AA34QVU0, A0AA34QW09, H7C270

UniProt curated annotations — full annotation on UniProt →

Function. Preferentially catalyzes the dephosphorylation of ‘Ser-5’ within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells.

Subunit / interactions. Monomer. Interacts with GTF2F1. Interacts with REST.

Subcellular location. Nucleus.

Tissue specificity. Expression is restricted to non-neuronal tissues. Highest expression in skeletal muscle, spleen, lung and placenta.

Activity regulation. Stimulated by GTF2F1. Inhibited by beryllofluoride anions.

Cofactor. Binds 1 Mg(2+) ion per monomer.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9GZU7-1	1	yes
Q9GZU7-2	2
Q9GZU7-3	3

RefSeq proteins (12): NP_001193807, NP_001387197, NP_001387198, NP_001387199, NP_001387200, NP_001387201, NP_001387202, NP_001387203, NP_001387204, NP_001387205, NP_067021, NP_872580 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004274	FCP1_dom	Domain
IPR011948	Dullard_phosphatase	Domain
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR040078	RNA_Pol_CTD_Phosphatase	Family
IPR050365	TIM50	Family

Pfam: PF03031

Catalyzed reactions (Rhea), 2 shown:

• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (41 total): strand 11, helix 10, binding site 3, site 2, splice variant 2, mutagenesis site 2, compositionally biased region 2, active site 2, chain 1, domain 1, modified residue 1, sequence variant 1, sequence conflict 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2GHT	X-RAY DIFFRACTION	1.8
2GHQ	X-RAY DIFFRACTION	2.05
1TA0	X-RAY DIFFRACTION	2.1
4YH1	X-RAY DIFFRACTION	2.2
1T9Z	X-RAY DIFFRACTION	2.3
3L0Y	X-RAY DIFFRACTION	2.3
3L0B	X-RAY DIFFRACTION	2.35
3PGL	X-RAY DIFFRACTION	2.35
4YGY	X-RAY DIFFRACTION	2.36
3L0C	X-RAY DIFFRACTION	2.45
6DU3	X-RAY DIFFRACTION	2.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZU7-F1	82.13	0.70

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 (4): 152 (transition state stabilizer); 190 (transition state stabilizer); 96 (4-aspartylphosphate intermediate); 98 (proton donor)

Ligand- & substrate-binding residues (3): 96; 98; 207

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (2):

Position	Phenotype
96	no effect. completely abolishes phosphatase activity; when associated with n-98.
98	completely abolishes phosphatase activity; when associated with e-96.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 232 (showing top): CREL_01, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, PAX4_01, SP3_Q3, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, AP4_Q6, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, AP2_Q3, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GTGCCTT_MIR506, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, E2F_Q3

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), protein dephosphorylation (GO:0006470), negative regulation of neuron differentiation (GO:0045665), negative regulation of neurogenesis (GO:0050768), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134)

GO Molecular Function (7): RNA polymerase II CTD heptapeptide repeat phosphatase activity (GO:0008420), metal ion binding (GO:0046872), phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
dephosphorylation	1
protein modification process	1
neuron differentiation	1
negative regulation of cell differentiation	1
regulation of neuron differentiation	1
negative regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
negative regulation of nervous system development	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
protein serine/threonine phosphatase activity	1
RNA polymerase II CTD heptapeptide repeat modifying activity	1
cation binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1189 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTDSP1	CTDP1	Q9Y5B0	868
CTDSP1	REST	Q13127	830
CTDSP1	UBLCP1	Q8WVY7	815
CTDSP1	NIF3L1	Q9GZT8	768
CTDSP1	SLC11A1	P49279	615
CTDSP1	GTF2F1	P35269	564
CTDSP1	CDCA3	Q99618	550
CTDSP1	ACTL6B	O94805	506
CTDSP1	PTBP1	P26599	502
CTDSP1	RCOR1	Q9UKL0	491
CTDSP1	ACTL6A	O96019	488
CTDSP1	LDB1	Q86U70	474
CTDSP1	SSU72	Q9NP77	444
CTDSP1	KDM5C	P41229	442
CTDSP1	KCNN4	O15554	428

IntAct

134 interactions, top by confidence:

A	B	Type	Score
CTDSP1	CDCA3	psi-mi:“MI:0915”(physical association)	0.940
CDCA3	CTDSP1	psi-mi:“MI:0915”(physical association)	0.940
CTDSP1	CDCA3	psi-mi:“MI:0914”(association)	0.940
CTDSP1	MBP	psi-mi:“MI:0915”(physical association)	0.740
MBP	CTDSP1	psi-mi:“MI:0915”(physical association)	0.740
MBP	CTDSP1	psi-mi:“MI:0915”(physical association)	0.670
CDCA3	CTDSPL	psi-mi:“MI:0914”(association)	0.670
CDA	LIN7A	psi-mi:“MI:0914”(association)	0.640
CTDSP1	CTDSPL	psi-mi:“MI:0914”(association)	0.640
MAPKBP1	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
ITPKB	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
FAM110A	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
ACTN3	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
CTDSP1	WWOX	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC6A	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
CDKN2C	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
FAAP20	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
MORN3	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
ZBTB16	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
CTDSP1	FANCL	psi-mi:“MI:0915”(physical association)	0.560
LCK	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
CTDSP1	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560
RAB3IL1	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
SCNM1	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (150): CTDSP1 (Two-hybrid), CDCA3 (Two-hybrid), CTDSP2 (Affinity Capture-MS), CTDSPL (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), HEATR6 (Affinity Capture-MS), DSTYK (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), CDCA3 (Affinity Capture-MS), FAM118B (Affinity Capture-MS), CDCA3 (Two-hybrid), REST (Affinity Capture-Western), CDCA3 (Affinity Capture-MS)

ESM2 similar proteins: A4QNX6, M9PFN0, O14595, O15194, O19111, O59697, O80673, P09217, P32019, P53681, P58465, P58466, Q00IB6, Q02956, Q05513, Q05D32, Q08BB5, Q09315, Q09695, Q14BI7, Q1EHT7, Q30DN6, Q3KQB6, Q3MHU3, Q5F3Z7, Q5XIK8, Q5XUN4, Q5ZI74, Q62240, Q66KM5, Q75WV3, Q801R4, Q8BG15, Q8BX07, Q8K337, Q8K4T5, Q8L7M4, Q8NDG6, Q8SV03, Q9BY66

Diamond homologs: A4QNX6, M9PFN0, O13636, O14595, O15194, O59718, O95476, P0CN66, P0CN67, P38757, P58465, P58466, Q02776, Q05D32, Q07800, Q07949, Q08BB5, Q09695, Q1RMV9, Q20432, Q28HW9, Q29I63, Q3B7T6, Q3KQB6, Q3TP92, Q3ZCQ8, Q4I099, Q4PEW9, Q4WI16, Q54GB2, Q59W44, Q5B4P0, Q5F3Z7, Q5RAJ8, Q5S7T7, Q5U395, Q5U3T3, Q5XIK8, Q61C05, Q66KM5

SIGNOR signaling

39 interactions.

A	Effect	B	Mechanism
CTDSP1	down-regulates	SMAD1	dephosphorylation
CTDSP1	“form complex”	NLI/Lmx1.1/Isl1	binding
CTDSP1	“down-regulates activity”	TWIST1	dephosphorylation
CTDSP1	“up-regulates activity”	SMAD3	dephosphorylation
CTDSP1	“down-regulates activity”	SMAD2	dephosphorylation
CTDSP1	“down-regulates activity”	SMAD1	dephosphorylation
CTDSP1	“up-regulates activity”	PRKDC	dephosphorylation
CTDSP1	“up-regulates activity”	POLR2A	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1153 predictions. Top by Δscore:

Variant	Effect	Δscore
2:218401711:AGGT:A	donor_loss	1.0000
2:218401713:GTGC:G	donor_loss	1.0000
2:218402109:A:AG	acceptor_gain	1.0000
2:218402110:G:GG	acceptor_gain	1.0000
2:218402110:GC:G	acceptor_gain	1.0000
2:218402110:GCA:G	acceptor_gain	1.0000
2:218402211:TCAAG:T	donor_loss	1.0000
2:218402212:CAAGG:C	donor_loss	1.0000
2:218402213:AAG:A	donor_loss	1.0000
2:218402214:AGG:A	donor_loss	1.0000
2:218402215:GGTG:G	donor_loss	1.0000
2:218402347:A:AG	acceptor_gain	1.0000
2:218402348:G:GG	acceptor_gain	1.0000
2:218402348:GCCA:G	acceptor_gain	1.0000
2:218402405:GGTGA:G	donor_loss	1.0000
2:218402406:G:C	donor_loss	1.0000
2:218402407:T:G	donor_loss	1.0000
2:218402417:G:GT	donor_gain	1.0000
2:218403033:A:AC	acceptor_loss	1.0000
2:218403128:GT:G	donor_loss	1.0000
2:218403129:T:G	donor_loss	1.0000
2:218403230:A:AG	acceptor_gain	1.0000
2:218403231:G:GG	acceptor_gain	1.0000
2:218403231:GTAC:G	acceptor_gain	1.0000
2:218403413:ATGCT:A	donor_gain	1.0000
2:218403417:TG:T	donor_loss	1.0000
2:218403418:G:GG	donor_gain	1.0000
2:218403418:GT:G	donor_loss	1.0000
2:218404292:CCCAG:C	acceptor_loss	1.0000
2:218404293:CCAG:C	acceptor_loss	1.0000

AlphaMissense

1698 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:218402175:T:A	V94D	1.000
2:218402178:T:A	I95N	1.000
2:218402180:G:C	D96H	1.000
2:218402181:A:C	D96A	1.000
2:218402181:A:T	D96V	1.000
2:218402182:C:A	D96E	1.000
2:218402182:C:G	D96E	1.000
2:218402184:T:A	L97Q	1.000
2:218402184:T:C	L97P	1.000
2:218402186:G:A	D98N	1.000
2:218402186:G:C	D98H	1.000
2:218402186:G:T	D98Y	1.000
2:218402187:A:C	D98A	1.000
2:218402187:A:G	D98G	1.000
2:218402187:A:T	D98V	1.000
2:218402188:C:A	D98E	1.000
2:218402188:C:G	D98E	1.000
2:218402190:A:C	E99A	1.000
2:218402190:A:T	E99V	1.000
2:218402191:G:C	E99D	1.000
2:218402191:G:T	E99D	1.000
2:218402192:A:C	T100P	1.000
2:218402193:C:T	T100I	1.000
2:218402196:T:A	L101Q	1.000
2:218402196:T:C	L101P	1.000
2:218402199:T:A	V102E	1.000
2:218402201:C:G	H103D	1.000
2:218402203:C:A	H103Q	1.000
2:218402203:C:G	H103Q	1.000
2:218402204:A:C	S104R	1.000

dbSNP variants (sampled 300 via entrez): RS1000027061 (2:218404221 G>A), RS1000081277 (2:218401932 C>G), RS1000331553 (2:218395095 G>A,C), RS1000480197 (2:218395644 G>A), RS1000637242 (2:218397792 GTAAC>G,GTAACTAAC), RS1000668580 (2:218397682 G>A), RS1000724276 (2:218396262 G>A), RS1000921583 (2:218405326 T>A,C), RS1000950661 (2:218406262 C>A,G,T), RS1000952394 (2:218405155 AC>A,ACC), RS1001071596 (2:218396158 G>C,T), RS1001577234 (2:218399498 A>G), RS1001637847 (2:218398468 C>T), RS1001753386 (2:218402042 A>G), RS1001828632 (2:218403196 C>T)

Disease associations

OMIM: gene MIM:605323 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001725_74	Inflammatory bowel disease	4.000000e-12
GCST004605_61	Mean corpuscular hemoglobin concentration	4.000000e-12
GCST90002387_60	Immature fraction of reticulocytes	2.000000e-21
GCST90002391_141	Mean corpuscular hemoglobin concentration	3.000000e-27

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795098 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 126,848 (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
CHEMBL1200347	ISOPROPAMIDE IODIDE	4	2,616
CHEMBL2146124	CEFUROXIME SODIUM	4	56
CHEMBL3561076	TRIMETAZIDINE DIHYDROCHLORIDE	4	280
CHEMBL617	CEPHALOTHIN	4	24,927
CHEMBL680	CEFACLOR ANHYDROUS	4	34,121
CHEMBL927	CEFDINIR	4	19,403
CHEMBL1716983	ENISAMIUM IODIDE	3	1
CHEMBL449317	HESPERIDIN	3	18,753
CHEMBL1257065	STILONIUM IODIDE	2	751
CHEMBL150	KAEMPFEROL	1	25,940

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

Binding affinities (BindingDB)

927 measured of 947 human assays (1011 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
3-(2-furanylmethyl)-2-propylthiochromeno[2,3-d]pyrimidine-4,5-dione	EC50	0.0148 nM
6-bromo-2-{[4-(2-furoyl)-1-piperazinyl]carbonyl}pyrazolo[1,5-a]pyrimidine	EC50	2.73 nM
4-[[2-[(4-keto-6-methyl-1H-pyrimidin-2-yl)thio]acetyl]amino]benzoic acid ethyl ester	IC50	23 nM
5-(tosylmethyl)-2-furoic acid	IC50	23 nM
3-[2-(hydroximinomethyl)pyrrol-1-yl]benzoic acid	IC50	23 nM
2-[(4-benzyl-5-methyl-1,2,4-triazol-3-yl)sulfanyl]-N-(furan-2-ylmethylcarbamoyl)acetamide	EC50	44.7 nM
cid_694792	KI	60 nM
MLS000122969	IC50	127 nM
MLS000082005	IC50	351 nM
MLS000562014	IC50	408 nM
SMR000199423	EC50	629 nM
(5E)-5-[(4-methoxy-3-methylphenyl)methylidene]-1-methyl-2-sulfanylidene-1,3-diazinane-4,6-dione	IC50	632 nM
N-[6-azanyl-2,4-bis(oxidanylidene)-1-(phenylmethyl)pyrimidin-5-yl]-N-propyl-3-pyrrol-1-yl-benzamide	EC50	720 nM
(E)-1-(1,3-dithiolan-2-ylidene)-4-(2-furanyl)-3-buten-2-one	EC50	781 nM
(E)-N-[2-[(N’‘E)-N’’-[1-(4-ethylphenyl)ethylidene]hydrazino]-2-keto-ethyl]-3-(2-furyl)acrylamide	IC50	844 nM
SMR000241765	IC50	1020 nM
cid_1728957	IC50	1020 nM
MLS001008494	IC50	1030 nM
MLS000531387	IC50	1050 nM
(E)-3-(3,4-dimethoxyphenyl)-N-[(2-hydroxy-5-nitro-phenyl)thiocarbamoyl]acrylamide	IC50	1090 nM
2-[3-[2-hydroxyethyl(dimethyl)azaniumyl]propanoylamino]-2-methyl-propane-1-sulfonate	EC50	1160 nM
AmB	IC50	1170 nM
2-[2,6-bis(chloranyl)-4-[(Z)-[3-[2-[(4-methylphenyl)amino]-2-oxidanylidene-ethyl]-2,4-bis(oxidanylidene)-1,3-thiazolidin-5-ylidene]methyl]phenoxy]ethanoic acid	IC50	1200 nM
2-{3-[(2-Hydroxy-benzoyl)-hydrazono]-2-oxo-2,3-dihydro-indol-1-yl}-N-o-tolyl-acetamide	IC50	1230 nM
cid_2480569	IC50	1380 nM
[4-[[(3,5-dihydroxybenzoyl)hydrazinylidene]methyl]phenyl] 2-chlorobenzoate	IC50	1400 nM
3-[((2Z)-5-[(acetyloxy)methyl]-3-{[(2,4-dimethoxyphenyl)amino]carbonyl}-8-methyl-2H-pyrano[2,3-c]pyridin-2-ylidene)amino]benzoic acid	IC50	1530 nM
(5Z)-2-azanylidene-3-(4-fluorophenyl)-5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidin-4-one	IC50	1550 nM
(5E)-5-[[5-[[(2-anilino-1,2-dioxoethyl)amino]methyl]-2-furanyl]methylidene]-2-methyl-4-oxo-1H-pyrrole-3-carboxylic acid ethyl ester	IC50	1560 nM
2-[(4-benzyl-5-thiophen-2-yl-1,2,4-triazol-3-yl)sulfanylmethyl]pyrimido[2,1-b][1,3]benzothiazol-4-one	IC50	1560 nM
MLS000673878	IC50	1570 nM
cid_4790991	IC50	1620 nM
3-(3-nitrophenyl)-N’-[(1E)-1-(6-oxo-1-cyclohexa-2,4-dienylidene)ethyl]-1H-pyrazole-5-carbohydrazide	IC50	1700 nM
N-[[(E)-3-phenylprop-2-enylidene]amino]-2-benzo[e]benzofurancarboxamide	IC50	1720 nM
(E)-2-(6-methyl-1H-benzimidazol-2-yl)-3-[5-(3-nitrophenyl)-2-furanyl]-2-propenenitrile	IC50	1750 nM
5-chloro-2-thiophenecarboxylic acid [4-[(E)-2-(1H-benzimidazol-2-yl)-2-cyanoethenyl]phenyl] ester	IC50	1770 nM
N-(3-methylphenyl)-2-[4-[(Z)-2-[5-nitro-2,4-bis(oxidanylidene)-1H-pyrimidin-6-yl]ethenyl]phenoxy]ethanamide	IC50	1780 nM
4-{2-[(5-bromo-3-pyridinyl)carbonyl]carbonohydrazonoyl}phenyl 1,3-benzodioxole-5-carboxylate	IC50	1800 nM
MLS000585164	IC50	1820 nM
5-bromo-2-thiophenecarboxylic acid [4-[(Z)-2-(1H-benzimidazol-2-yl)-2-cyanoethenyl]phenyl] ester	IC50	1820 nM
MLS-0336006.0001	IC50	1830 nM
4-(5,5-dimethyl-3-morpholin-4-ylcyclohex-2-en-1-ylidene)-2,6-dimethylmorpholin-4-ium;iodide	IC50	1830 nM
MLS000773704	IC50	1850 nM
MLS001211762	IC50	1880 nM
N’-(3-chlorobenzoyl)thieno[2,3-b]quinoline-2-carbohydrazide	IC50	1900 nM
(2Z)-5-amino-2-(2-furfurylidene)-7-(2-furyl)-3-keto-7H-thiazolo[3,2-a]pyridine-6,8-dicarbonitrile	IC50	1920 nM
(8S)-7-(3,3-diphenylpropanoyl)-3-[3-(2-methylprop-2-enoylamino)phenyl]-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	EC50	1940 nM
MLS000548432	IC50	1990 nM
3-[7-[(2-chlorophenyl)methoxy]-4,8-dimethyl-2-oxochromen-3-yl]propanoic acid	IC50	1990 nM
cid_5754238	IC50	2000 nM

ChEMBL bioactivities

779 potent at pChembl≥5 of 1003 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.39	IC50	408	nM	CHEMBL1464280
6.34	IC50	453	nM	CHEMBL1533230
6.27	IC50	540	nM	CHEMBL1360585
6.20	IC50	632	nM	CHEMBL1477703
6.15	IC50	711	nM	CHEMBL1309432
6.13	IC50	737	nM	CHEMBL3212539
6.08	IC50	836	nM	CHEMBL1325664
6.07	IC50	844	nM	CHEMBL1967028
6.05	IC50	900	nM	CHEMBL1517799
5.99	IC50	1027	nM	CHEMBL1461216
5.99	IC50	1025	nM	CHEMBL1361920
5.99	IC50	1017	nM	CHEMBL1735048
5.95	IC50	1120	nM	CHEMBL1324382
5.93	IC50	1169	nM	CHEMBL1700818
5.91	IC50	1227	nM	CHEMBL598477
5.91	IC50	1231	nM	CHEMBL1374955
5.86	IC50	1375	nM	CHEMBL1557036
5.86	IC50	1396	nM	CHEMBL1978925
5.84	IC50	1444	nM	CHEMBL1481493
5.84	IC50	1455	nM	CHEMBL3856092
5.81	IC50	1544	nM	CHEMBL3194164
5.81	IC50	1552	nM	CHEMBL1560629
5.80	IC50	1567	nM	CHEMBL1538387
5.80	IC50	1595	nM	CHEMBL1374016
5.79	IC50	1603	nM	CHEMBL1485960
5.79	IC50	1615	nM	CHEMBL1322848
5.79	IC50	1614	nM	CHEMBL1510349
5.77	IC50	1700	nM	CHEMBL1975756
5.76	IC50	1718	nM	CHEMBL3197136
5.76	IC50	1719	nM	CHEMBL1305930
5.76	IC50	1734	nM	CHEMBL1340117
5.75	IC50	1768	nM	CHEMBL1528986
5.75	IC50	1800	nM	CHEMBL3198331
5.75	IC50	1779	nM	CHEMBL1501349
5.75	IC50	1777	nM	CHEMBL1575221
5.74	IC50	1828	nM	CHEMBL1977271
5.74	IC50	1828	nM	CHEMBL1390354
5.74	IC50	1838	nM	CHEMBL1469245
5.74	IC50	1818	nM	CHEMBL1883674
5.74	IC50	1830	nM	CHEMBL1566816
5.73	IC50	1879	nM	CHEMBL1302375
5.73	IC50	1847	nM	CHEMBL3195249
5.73	IC50	1878	nM	CHEMBL1443718
5.73	IC50	1857	nM	CHEMBL1612081
5.72	IC50	1896	nM	CHEMBL1331974
5.72	IC50	1894	nM	CHEMBL1368108
5.72	IC50	1889	nM	CHEMBL5483017
5.70	IC50	1988	nM	CHEMBL1466471
5.70	IC50	2002	nM	CHEMBL1490134
5.70	IC50	2000	nM	CHEMBL1342081

PubChem BioAssay actives

3 with measured affinity, of 17 total; 2 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
1,1-dioxo-N-[3-[[4-(trifluoromethoxy)phenyl]sulfonylamino]propyl]-1-benzothiophene-2-carboxamide	1824654: Covalent inhibition of wild type human SCP1 assessed as inhibition constant using Ac-EDLphosphoSPPSPPLPK-NH2 peptide as substrate preincubated for 0.5 to 18 hrs followed by substrate addition by malachite green reagent based assay	ki	4.8000	uM
1,1-dioxo-N-[2-[2-[[4-(trifluoromethoxy)phenyl]sulfonylamino]ethoxy]ethyl]-1-benzothiophene-2-carboxamide	1824652: Inhibition of wild type human SCP1 using pNPP as substrate incubated for 0.5 to 18 hrs followed by substrate addition by absorbance based analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	5
mercuric bromide	decreases expression, affects cotreatment	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	2
Ozone	increases oxidation, increases abundance, decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cadmium Chloride	decreases expression, decreases reaction, increases abundance, increases palmitoylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	decreases expression	1
trichostatin A	affects expression	1
afimoxifene	decreases expression, decreases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
arsenic disulfide	affects expression	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	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
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1

ChEMBL screening assays

11 unique, capped per target: 10 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1794574	Functional	PUBCHEM_BIOASSAY: Dose Response confirmation of uHTS hits for Scp-1 phosphatase using a colorimetric assay. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID493091, AID493120]	PubChem BioAssay data set
CHEMBL3429233	Binding	Inhibition of SCP1 (unknown origin) using pNPP as substrate at pH 7 at 25 degC by spectrophotometric analysis	A potent and selective inhibitor for the UBLCP1 proteasome phosphatase. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2VD	Abcam HEK293T CTDSP1 KO	Transformed cell line	Female
CVCL_SK00	HAP1 CTDSP1 (-) 1	Cancer cell line	Male
CVCL_SK01	HAP1 CTDSP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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