CTDSPL2

Summary

CTDSPL2 (CTD small phosphatase like 2, HGNC:26936) is a protein-coding gene on chromosome 15q15.3-q21.1, encoding CTD small phosphatase-like protein 2 (Q05D32). Serine/threonine phosphatase that promotes gluconeogenesis by dephosphorylating FOXO1 and FOXO3A, promoting their nuclear retention and enhancing their transcriptional activity on PCK1 and G6PC1, key enzymes in hepatic gluconeogenesis.

Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of BMP signaling pathway; positive regulation of protein export from nucleus; and protein dephosphorylation. Located in nucleoplasm.

Source: NCBI Gene 51496 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 77 total — 1 pathogenic
• MANE Select transcript: NM_016396

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26936
Approved symbol	CTDSPL2
Name	CTD small phosphatase like 2
Location	15q15.3-q21.1
Locus type	gene with protein product
Status	Approved
Aliases	HSPC129, FLJ10523
Ensembl gene	ENSG00000137770
Ensembl biotype	protein_coding
OMIM	618739
Entrez	51496

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000260327, ENST00000558373, ENST00000558791, ENST00000558966, ENST00000558968, ENST00000559175, ENST00000559738, ENST00000559793, ENST00000560620, ENST00000560834, ENST00000561189, ENST00000872547, ENST00000872548, ENST00000872549, ENST00000872550, ENST00000872551, ENST00000937565

RefSeq mRNA: 1 — MANE Select: NM_016396 NM_016396

CCDS: CCDS10110

Canonical transcript exons

ENST00000260327 — 13 exons

Exon	Start	End
ENSE00000475284	44490784	44490999
ENSE00000684172	44484224	44484362
ENSE00000684233	44486551	44486700
ENSE00001870130	44427629	44427772
ENSE00001887838	44524109	44529038
ENSE00003465947	44497027	44497138
ENSE00003480411	44514598	44514660
ENSE00003483817	44496380	44496458
ENSE00003513937	44521311	44521406
ENSE00003613575	44519169	44519295
ENSE00003657543	44458991	44459200
ENSE00003662146	44514765	44514844
ENSE00003692581	44499727	44499813

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.6361 / max 422.9215, expressed in 1804 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146369	32.4762	1804
146371	0.0923	32
146370	0.0677	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.27	gold quality
buccal mucosa cell	CL:0002336	96.50	gold quality
colonic epithelium	UBERON:0000397	93.71	gold quality
secondary oocyte	CL:0000655	93.59	gold quality
sural nerve	UBERON:0015488	93.19	gold quality
adrenal tissue	UBERON:0018303	93.16	gold quality
oviduct epithelium	UBERON:0004804	92.56	gold quality
epithelial cell of pancreas	CL:0000083	92.37	silver quality
ventricular zone	UBERON:0003053	92.33	gold quality
cortical plate	UBERON:0005343	91.75	gold quality
ganglionic eminence	UBERON:0004023	91.21	gold quality
embryo	UBERON:0000922	91.20	gold quality
cartilage tissue	UBERON:0002418	91.07	gold quality
bone marrow cell	CL:0002092	90.65	gold quality
tendon	UBERON:0000043	89.99	gold quality
tibialis anterior	UBERON:0001385	89.11	gold quality
oocyte	CL:0000023	89.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.90	gold quality
ileal mucosa	UBERON:0000331	88.33	gold quality
islet of Langerhans	UBERON:0000006	88.31	gold quality
smooth muscle tissue	UBERON:0001135	87.55	gold quality
vermiform appendix	UBERON:0001154	86.19	gold quality
gall bladder	UBERON:0002110	86.16	gold quality
monocyte	CL:0000576	85.92	gold quality
leukocyte	CL:0000738	85.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.82	gold quality
pancreatic ductal cell	CL:0002079	85.81	silver quality
sperm	CL:0000019	85.75	gold quality
bone marrow	UBERON:0002371	85.60	gold quality
rectum	UBERON:0001052	85.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.10
E-MTAB-6142	no	186.54

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
HBE1	Activation
HBG1	Activation
HBG2	Activation

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

293 targeting CTDSPL2, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084

Literature-anchored findings (GeneRIF, showing 8)

• increases epsilon- and gamma-globin gene expression during erythroid differentiation (PMID:20932329)
• proteomic screening was conducted to identify binding partners of CTDSPL2 in nuclear extract through immunoprecipitation of CTDSPL2 with its associated. (PMID:26674342)
• SCP4 is a unique chromatin-associated, Ser5-preferential CTD phosphatase that preferentially distributes to transcriptionally silenced gene regions and may participate in gene regulation during erythroid differentiation. (PMID:26920047)
• expression significantly increased in skeletal muscle of chronic kidney disease patients (PMID:28506762)
• CTD small phosphatase like 2 plays a critical role in EMT through Snail dephosphorylation and stabilization. (PMID:29618518)
• The phosphatase CTDSPL2 is phosphorylated in mitosis and a target for restraining tumor growth and motility in pancreatic cancer. (PMID:34813892)
• SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia. (PMID:35021089)
• Hypermethylation of CTDSPL2 prior to necrotizing enterocolitis onset. (PMID:37309586)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctdspl2b	ENSDARG00000060586
danio_rerio	ctdspl2a	ENSDARG00000061587
mus_musculus	Ctdspl2	ENSMUSG00000033411
rattus_norvegicus	Ctdspl2	ENSRNOG00000022141
caenorhabditis_elegans	scpl-3	WBGENE00021629

Paralogs (5): TIMM50 (ENSG00000105197), CTDSP1 (ENSG00000144579), CTDSPL (ENSG00000144677), CTDSP2 (ENSG00000175215), CTDNEP1 (ENSG00000175826)

Protein

Protein identifiers

CTD small phosphatase-like protein 2 — Q05D32 (reviewed: Q05D32)

Alternative names: Small C-terminal domain phosphatase 4

All UniProt accessions (5): Q05D32, H0YMB4, H0YMH7, H0YNU2, H0YNW9

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine phosphatase that promotes gluconeogenesis by dephosphorylating FOXO1 and FOXO3A, promoting their nuclear retention and enhancing their transcriptional activity on PCK1 and G6PC1, key enzymes in hepatic gluconeogenesis. Essential for proper embryonic skeletal development by regulating chondrocyte survival through dephosphorylation of FOXO3. By maintaining FOXO3 in its active, dephosphorylated form, inhibits excessive apoptosis of chondrocytes, which is essential for normal endochondral ossification and cartilage formation.

Subunit / interactions. Interacts with FOXO1 and FOXO3.

Subcellular location. Nucleus.

Similarity. Belongs to the CTDSPL2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q05D32-1	1	yes
Q05D32-2	2

RefSeq proteins (1): NP_057480* (*=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
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 (22 total): modified residue 9, sequence conflict 3, compositionally biased region 3, region of interest 2, chain 1, domain 1, splice variant 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05D32-F1	66.94	0.44

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 (9): 57, 85, 86, 104, 134, 165, 26, 28, 51

Mutagenesis-validated functional residues (1):

Position	Phenotype
295	loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 327 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, E2F_Q4, CREL_01, E2F_Q4_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, WANG_CLIM2_TARGETS_UP, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CARTILAGE_DEVELOPMENT, E2F4DP1_01, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT

GO Biological Process (9): growth plate cartilage chondrocyte growth (GO:0003430), protein export from nucleus (GO:0006611), negative regulation of BMP signaling pathway (GO:0030514), positive regulation of gluconeogenesis (GO:0045722), positive regulation of protein export from nucleus (GO:0046827), embryonic skeletal system development (GO:0048706), cartilage development (GO:0051216), bone development (GO:0060348), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (6): phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), RNA polymerase II CTD heptapeptide repeat phosphatase activity (GO:0008420), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
skeletal system development	3
animal organ development	2
chondrocyte hypertrophy	1
growth plate cartilage chondrocyte development	1
developmental growth involved in morphogenesis	1
intracellular protein transport	1
nuclear export	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
gluconeogenesis	1
regulation of gluconeogenesis	1
positive regulation of biosynthetic process	1
positive regulation of glucose metabolic process	1
protein export from nucleus	1
positive regulation of nucleocytoplasmic transport	1
regulation of protein export from nucleus	1
positive regulation of intracellular protein transport	1
chordate embryonic development	1
connective tissue development	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
protein serine/threonine phosphatase activity	1
RNA polymerase II CTD heptapeptide repeat modifying activity	1
binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1433 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTDSPL2	KLHDC1	Q8N7A1	502
CTDSPL2	UBLCP1	Q8WVY7	486
CTDSPL2	GAS2L1	Q99501	477
CTDSPL2	OGFOD2	Q6N063	402
CTDSPL2	ZCRB1	Q8TBF4	389
CTDSPL2	PGPEP1L	A6NFU8	370
CTDSPL2	ANAPC13	Q9BS18	368
CTDSPL2	PPM1A	P35813	363
CTDSPL2	CTDP1	Q9Y5B0	359
CTDSPL2	DCAF6	Q58WW2	357
CTDSPL2	RPAP2	Q8IXW5	356
CTDSPL2	AGGF1	Q8N302	350
CTDSPL2	ZNF439	Q8NDP4	349
CTDSPL2	TMEM135	Q86UB9	337
CTDSPL2	PRPSAP2	O60256	336

IntAct

30 interactions, top by confidence:

A	B	Type	Score
CTDSPL2	PDIK1L	psi-mi:“MI:0915”(physical association)	0.840
PDIK1L	CTDSPL2	psi-mi:“MI:0914”(association)	0.840
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
CTDSPL2	KPNA4	psi-mi:“MI:0915”(physical association)	0.560
STK35	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
PDIK1L	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
CTDSPL2	nleC	psi-mi:“MI:0915”(physical association)	0.370
CTDSPL2	ELOC	psi-mi:“MI:0914”(association)	0.350
PDIK1L	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
STK35	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
CTDSPL2	KPNA3	psi-mi:“MI:0914”(association)	0.350
PDIK1L	CSTB	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
MYO1E	MYO1C	psi-mi:“MI:0914”(association)	0.350
NUMA1	SHANK3	psi-mi:“MI:0914”(association)	0.350
KPNA2	SETD1A	psi-mi:“MI:0914”(association)	0.350
ELFN2	TBC1D4	psi-mi:“MI:0914”(association)	0.350
KPNA2	TAF4	psi-mi:“MI:0914”(association)	0.350
CTDSPL2	PDIK1L	psi-mi:“MI:0915”(physical association)	0.000
PDIK1L	CTDSPL2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (101): ATP5E (Affinity Capture-MS), IPP (Affinity Capture-MS), JAK1 (Affinity Capture-MS), MYBL2 (Affinity Capture-MS), RPL10 (Affinity Capture-MS), TCEB1 (Affinity Capture-MS), CDC42BPA (Affinity Capture-MS), SLC27A2 (Affinity Capture-MS), MED15 (Affinity Capture-MS), FBXL19 (Affinity Capture-MS), SCYL1 (Affinity Capture-MS), KLF16 (Affinity Capture-MS), CPNE8 (Affinity Capture-MS), CTDSPL2 (Synthetic Lethality), KPNA2 (Affinity Capture-MS)

ESM2 similar proteins: A3KFM7, A3KMI0, A4QNX6, B2KF05, B2RRD7, F4JZ68, F7BJB9, G5E8P1, M9PFN0, O16810, O80528, P55201, Q05D32, Q08BB5, Q09695, Q13415, Q1LYM3, Q24558, Q3KQB6, Q3U1T9, Q4R8E0, Q58DC8, Q5F3Z7, Q5FVG2, Q5SPR8, Q5XIK8, Q640I9, Q66KM5, Q68F67, Q6IVY4, Q6P158, Q6P3S1, Q6P5D3, Q7Z478, Q801R4, Q803U7, Q80Z32, Q8BG15, Q8BGS1, Q8CDK2

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

8 interactions.

A	Effect	B	Mechanism
CTDSPL2	“up-regulates quantity by expression”	HBG2	“transcriptional regulation”
CTDSPL2	“up-regulates quantity by expression”	HBG1	“transcriptional regulation”
CTDSPL2	“up-regulates quantity by expression”	HBE1	“transcriptional regulation”
CTDSPL2	“up-regulates quantity by stabilization”	STK35/PDIK1L	dephosphorylation
CTDSPL2	“up-regulates quantity by stabilization”	PDIK1L	dephosphorylation
CTDSPL2	“up-regulates quantity by stabilization”	STK35	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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
Viral Infection Pathways	5	11.0×	2e-03
Infectious disease	6	10.6×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	51
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564197	GRCh37/hg19 15q15.3-21.3(chr15:43759773-53252240)x1	Pathogenic

SpliceAI

3014 predictions. Top by Δscore:

Variant	Effect	Δscore
15:44458986:TTTAG:T	acceptor_loss	1.0000
15:44458987:TTAGT:T	acceptor_loss	1.0000
15:44458989:A:AG	acceptor_gain	1.0000
15:44458989:AGTTT:A	acceptor_loss	1.0000
15:44458990:G:GG	acceptor_gain	1.0000
15:44458990:GT:G	acceptor_gain	1.0000
15:44458990:GTT:G	acceptor_gain	1.0000
15:44458990:GTTT:G	acceptor_gain	1.0000
15:44458990:GTTTT:G	acceptor_gain	1.0000
15:44484214:A:AG	acceptor_gain	1.0000
15:44484215:T:G	acceptor_gain	1.0000
15:44484216:A:AG	acceptor_gain	1.0000
15:44484217:T:G	acceptor_gain	1.0000
15:44484219:TTAA:T	acceptor_loss	1.0000
15:44484221:AAG:A	acceptor_gain	1.0000
15:44484222:A:AG	acceptor_gain	1.0000
15:44484222:AGG:A	acceptor_loss	1.0000
15:44484223:G:GA	acceptor_loss	1.0000
15:44484223:G:GG	acceptor_gain	1.0000
15:44484223:GGAA:G	acceptor_gain	1.0000
15:44484333:GA:G	donor_gain	1.0000
15:44484335:G:GG	donor_gain	1.0000
15:44484348:GTCAA:G	donor_gain	1.0000
15:44484353:G:GG	donor_gain	1.0000
15:44484360:G:GT	donor_gain	1.0000
15:44484362:GGTT:G	donor_loss	1.0000
15:44484363:G:A	donor_loss	1.0000
15:44484364:T:A	donor_loss	1.0000
15:44486548:TAGAA:T	acceptor_gain	1.0000
15:44486549:A:AG	acceptor_gain	1.0000

AlphaMissense

3037 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:44486649:G:T	G142W	1.000
15:44496451:T:C	F255L	1.000
15:44496452:T:C	F255S	1.000
15:44496453:T:A	F255L	1.000
15:44496453:T:G	F255L	1.000
15:44496458:C:A	P257H	1.000
15:44497034:T:C	F260L	1.000
15:44497035:T:C	F260S	1.000
15:44497035:T:G	F260C	1.000
15:44497036:C:A	F260L	1.000
15:44497036:C:G	F260L	1.000
15:44497038:T:A	I261N	1.000
15:44497038:T:G	I261S	1.000
15:44497047:T:A	V264D	1.000
15:44497086:C:A	A277D	1.000
15:44497089:T:A	L278H	1.000
15:44497089:T:C	L278P	1.000
15:44497089:T:G	L278R	1.000
15:44497092:C:A	P279Q	1.000
15:44497101:C:T	T282I	1.000
15:44497104:G:C	R283T	1.000
15:44497104:G:T	R283I	1.000
15:44497105:A:C	R283S	1.000
15:44497105:A:T	R283S	1.000
15:44497122:C:T	S289F	1.000
15:44497125:T:A	L290Q	1.000
15:44497125:T:C	L290P	1.000
15:44497125:T:G	L290R	1.000
15:44497127:G:T	V291F	1.000
15:44497128:T:A	V291D	1.000

dbSNP variants (sampled 300 via entrez): RS1000004969 (15:44462483 C>A), RS1000058535 (15:44436004 A>G), RS1000065786 (15:44500045 C>T), RS1000088559 (15:44504145 C>G,T), RS1000101225 (15:44456261 G>C), RS1000194059 (15:44459842 T>C), RS1000227830 (15:44479008 T>C), RS1000240130 (15:44509830 G>T), RS1000271096 (15:44439543 T>A,G), RS1000283682 (15:44433225 G>A), RS1000298603 (15:44428341 G>T), RS1000383750 (15:44523061 A>G), RS1000384327 (15:44448664 C>T), RS1000389782 (15:44428118 T>C,G), RS1000403497 (15:44464959 G>A,T)

Disease associations

OMIM: gene MIM:618739 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST004630_159	Mean corpuscular hemoglobin	2.000000e-10
GCST007726_4	Anti-Toxoplasma gondii IgG seropositivity	5.000000e-06
GCST008070_4	HDL cholesterol levels	3.000000e-07
GCST008074_123	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-11
GCST008074_146	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5.000000e-12
GCST008075_109	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-16
GCST008075_40	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	6.000000e-16
GCST008076_43	Triglyceride levels	2.000000e-07
GCST008076_72	Triglyceride levels	3.000000e-06
GCST008083_115	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-12
GCST008083_8	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-10
GCST008084_183	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1.000000e-17
GCST008084_19	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-13
GCST008085_13	HDL cholesterol levels in current drinkers	9.000000e-06
GCST008085_164	HDL cholesterol levels in current drinkers	8.000000e-09
GCST008085_30	HDL cholesterol levels in current drinkers	5.000000e-11
GCST008087_127	Triglyceride levels in current drinkers	2.000000e-10
GCST008087_17	Triglyceride levels in current drinkers	4.000000e-11
GCST90002390_413	Mean corpuscular hemoglobin	3.000000e-16
GCST90002391_147	Mean corpuscular hemoglobin concentration	2.000000e-09
GCST90002392_426	Mean corpuscular volume	2.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0007047	Toxoplasma gondii seropositivity
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004329	alcohol drinking
EFO:0004528	mean corpuscular hemoglobin concentration

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	4
Valproic Acid	decreases expression	4
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
quercitrin	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	decreases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery