TFF1

Summary

TFF1 (trefoil factor 1, HGNC:11755) is a protein-coding gene on chromosome 21q22.3, encoding Trefoil factor 1 (P04155). Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents.

Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer, and affect healing of the epithelium. This gene, which is expressed in the gastric mucosa, has also been studied because of its expression in human tumors. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.

Source: NCBI Gene 7031 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_003225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11755
Approved symbol	TFF1
Name	trefoil factor 1
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	D21S21, HPS2, pS2, pNR-2, HP1.A
Ensembl gene	ENSG00000160182
Ensembl biotype	protein_coding
OMIM	113710
Entrez	7031

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000291527

RefSeq mRNA: 1 — MANE Select: NM_003225 NM_003225

CCDS: CCDS13685

Canonical transcript exons

ENST00000291527 — 3 exons

Exon	Start	End
ENSE00001050346	42366411	42366535
ENSE00001050347	42363255	42363407
ENSE00001368209	42362282	42362495

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 99.89.

FANTOM5 (CAGE): breadth broad, TPM avg 103.2231 / max 9675.8357, expressed in 232 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190614	103.2231	232

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.89	gold quality
endometrium epithelium	UBERON:0004811	99.64	gold quality
mucosa of stomach	UBERON:0001199	99.61	gold quality
palpebral conjunctiva	UBERON:0001812	99.19	gold quality
pylorus	UBERON:0001166	99.16	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.65	gold quality
ileal mucosa	UBERON:0000331	98.17	gold quality
gall bladder	UBERON:0002110	97.93	gold quality
colonic mucosa	UBERON:0000317	97.50	gold quality
cardia of stomach	UBERON:0001162	97.25	gold quality
epithelial cell of pancreas	CL:0000083	96.90	gold quality
rectum	UBERON:0001052	95.62	gold quality
jejunal mucosa	UBERON:0000399	95.17	gold quality
nasal cavity epithelium	UBERON:0005384	94.03	gold quality
stomach	UBERON:0000945	93.40	gold quality
body of stomach	UBERON:0001161	93.30	gold quality
duodenum	UBERON:0002114	92.94	gold quality
trachea	UBERON:0003126	91.34	gold quality
mucosa of transverse colon	UBERON:0004991	89.73	gold quality
nasal cavity mucosa	UBERON:0001826	89.40	gold quality
fundus of stomach	UBERON:0001160	88.66	gold quality
mammary duct	UBERON:0001765	87.75	gold quality
epithelium of mammary gland	UBERON:0003244	87.41	gold quality
urethra	UBERON:0000057	86.92	gold quality
islet of Langerhans	UBERON:0000006	86.76	gold quality
type B pancreatic cell	CL:0000169	86.55	gold quality
olfactory bulb	UBERON:0002264	86.13	gold quality
diaphragm	UBERON:0001103	86.08	gold quality
pharyngeal mucosa	UBERON:0000355	85.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.33	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	18462.93
E-MTAB-8410	yes	7672.38
E-GEOD-89232	yes	482.66
E-GEOD-125970	yes	23.09
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
KISS1

Upstream regulators (CollecTRI, top): AIP, AP1, BRCA1, CEBPB, E2F6, ESR1, ESR2, ESRRA, FOXA1, FOXA2, FOXO3, GATA3, GATA6, HDAC1, HIF1A, HMGN1, ID2, ID4, JUN, MECP2, MTA1, NCOA4, NELFB, NFATC3, NFATC4, NFKB1, NFKB, NR5A2, PGR, RELA, RFX4, SP1, SP3, STAT1, TFAP2C, USF1, ZBTB17

miRNA regulators (miRDB)

6 targeting TFF1, 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-4775	99.98	75.00	6394
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-6869-5P	97.17	67.06	634
HSA-MIR-5704	94.82	67.46	448

Literature-anchored findings (GeneRIF, showing 40)

• The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis. (PMID:12034770)
• Loss of heterozygosity and promoter methylation, but not mutation, may underlie loss in gastric carcinoma (PMID:12379766)
• Expressed in conjunctiva in goblet cells. Review. (PMID:12613926)
• Decreased TFF1 expression may lead to increased cell proliferation and then to the invasive character of intrahepatic cholangiocarcinoma. (PMID:14563942)
• TFF1 may play an as yet undetermined role in the tumorigenesis of colorectal carcinomas. (PMID:14756547)
• increased TFF1 and 2 concentrations found in serum from inflammatory bowel disease patients (PMID:15115253)
• H. pylori interacts avidly with the dimeric form of TFF1, and this interaction enables binding to gastric mucin, suggesting that TFF1 may act as a receptor for the organism in vivo (PMID:15123808)
• TFF1 is associated with the cell membrane of MCF-7 cells and is not linked via a GPI anchor. (PMID:15177868)
• Sp1 or Sp3 aid in recruitment of HDACs and histone acetyltransferases (HATs) to mediate dynamic acetylation of histones associated with the TFF1 promoter (PMID:15541729)
• The group of trefoil factor peptides (TFF1-3) are part of the protective mechanism operating in the intestinal mucosa and play a fundamental role in epithelial protection, repair, and restitution. (PMID:15578191)
• trefoil factor family protein 1(TFF1)is expressed in inflamed non-neoplastic gallbladder epithelium and in low stage and low grade gallbladder carcinomas (PMID:15821928)
• Decreased expression of TFF1 in carcinoma and its relativity to the differentiation suggests that TFF1 is related to gland and cell destruction of carcinoma. (PMID:15849833)
• This is the first demonstration that a member of the trefoil factor family of proteins, TFF1, is bound covalently to a brichos domain-containing protein, TFIZ1; this has profound implications for TFF1 function. (PMID:15924415)
• TFF-1 is lost late in the progression from Barrett’s Esophagus to adenocarcinoma, while CES-2 is upregulated (PMID:15967118)
• MUC5AC and MUC2, TFF1 and TFF3, APC and p21 in subsets of colorectal polyps and cancers suggests a distinct pathway of pathogenesis of mucinous carcinoma of the colorectum (PMID:16142311)
• TFF1, TFF2, TFF3 and MUC5AC may have roles in pathogenesis of pterygium goblet cells (PMID:16142316)
• urinary TFF1 is a CaOx crystal growth inhibitor with a potential pathophysiological role in nephrolithiasis (PMID:16308573)
• TFF1 showed a statistically significant difference between early-onset gastric cancers and conventional gastric cancers. (PMID:16474375)
• TFF1 and Cdc25A-B cooperate with other dominant oncogenic pathways to induce the adenoma and adenocarcinoma transitions. (PMID:16715141)
• reduced expression of TFF1 and TFF2 in precancerous conditions and gastric cancer may be associated with the proliferation and malignant transformation of gastric mucosa (PMID:16718800)
• D21S1893-D21S1890 region may harbor candidate genes especially TFF (TFF1, TFF2, and TFF3) and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. (PMID:16830362)
• SET-mediated promoter hypoacetylation is a prerequisite for coactivation of the estrogen-responsive pS2 gene by PRMT1 (PMID:16861234)
• Weaker expression of TFF1 in poorly-differentiated carcinoma may be related to the destruction of glands and cells in cancer tissues and the decrease in secretion of TFF1. (PMID:17143957)
• IGF-1 induces phosphorylation and an increase of the AP1 complex, which is phosphorylated and binds to the pS2/TFF1 promoter, allowing recruitment of the chromatin remodeling factor Brg1 followed by binding of ERalpha via its interaction with c-Jun (PMID:17317669)
• The study demonstrated a selective binding affinity of TFF1 for copper. (PMID:17610997)
• reveal a new property of TFF1 and suggest that copper could influence its biological activities by interfering with the dimerization of the peptide and/or the interaction with mucins or putative TFF receptors. (PMID:17610997)
• The effect of plant-derived and synthetic estrogens on estrogen receptor alpha medicated cell proliferation and estrogen-regulated pS2 expression in MCF-2 cells are reported. (PMID:17651883)
• The TFF1-GKN2 heterodimer and TFF2 differ characteristically by their binding to gastric mucins. (PMID:17982272)
• Periodic, strand-specific methylation/demethylation occurs during transcriptional cycling of the pS2/TFF1 gene promoter on activation by oestrogens (PMID:18322525)
• TFF was present in term and preterm human milk with rapidly declining concentrations during the first weeks post partum. (PMID:18502057)
• TFF1 protects Chang conjunctival cells from apoptosis induced by UV irradiation and benzalkonium chloride, by preventing caspase-8 activation. (PMID:18515572)
• The co-occupancy of ERalpha and Sp1 on TFF1 promoter remains at similar level with and without estrogen, while that of ERalpha and Sp3 increased in the presence of estrogen (PMID:18543253)
• Results describe the effects of estradiol on cyclin D1, PS2, and c-fos gene expression by measuring levels of RNA polymerase II on DNA templates, levels of nascent transcripts associated with RNA polymerase II, and levels of RNAs. (PMID:18644870)
• These data suggest that highly active chromatin is not only permissive for transcription, but can override the requirement for the transcription factor at an inducible promoter. (PMID:18662686)
• in gastric cancer, expression of TFF1 in the absence of TFIZ1 is associated with lymph node metastasis (PMID:18722547)
• Breast cancer patients with pre-operative elevated bone marrow levels of Mammaglobin Aand/or trefoil factor 1 mRNA seem to constitute a small group of patients with a very poor prognosis. (PMID:18846421)
• Decreased expression of TFF1 is associated with barrett’s esophagus-associated high-grade dysplasia. (PMID:18927283)
• High sensitivity of pS2 expression in prostate carcinoma could make it a suitable marker for diagnosis of prostate carcinoma, especially in metastatic cases of unknown origin. (PMID:19132993)
• This study demonstrates the over-expression in CTSE, in particular, and TFF1 in sessile serrated adenomas compared to both hyperplastic polyps and tubular adenomas. (PMID:19172291)
• circulating TFFs are not candidate markers of trisomy 21 in first-trimester pregnancies (PMID:19172695)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tff1	ENSMUSG00000024032
rattus_norvegicus	Tff1	ENSRNOG00000001164

Paralogs (2): TFF3 (ENSG00000160180), TFF2 (ENSG00000160181)

Protein

Protein identifiers

Trefoil factor 1 — P04155 (reviewed: P04155)

Alternative names: Breast cancer estrogen-inducible protein, PNR-2, Polypeptide P1.A, Protein pS2

All UniProt accessions (1): P04155

UniProt curated annotations — full annotation on UniProt →

Function. Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. May inhibit the growth of calcium oxalate crystals in urine.

Subunit / interactions. Heterodimer with GKN2; disulfide linked.

Subcellular location. Secreted.

Tissue specificity. Found in stomach, with highest levels in the upper gastric mucosal cells (at protein level). Detected in goblet cells of the small and large intestine and rectum, small submucosal glands in the esophagus, mucous acini of the sublingual gland, submucosal glands of the trachea, and epithelial cells lining the exocrine pancreatic ducts but not in the remainder of the pancreas (at protein level). Scattered expression is detected in the epithelial cells of the gallbladder and submucosal glands of the vagina, and weak expression is observed in the bronchial goblet cells of the pseudostratified epithelia in the respiratory system (at protein level). Detected in urine (at protein level). Strongly expressed in breast cancer but at low levels in normal mammary tissue. It is regulated by estrogen in MCF-7 cells. Strong expression found in normal gastric mucosa and in the regenerative tissues surrounding ulcerous lesions of gastrointestinal tract, but lower expression found in gastric cancer (at protein level).

RefSeq proteins (1): NP_003216* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000519	P_trefoil_dom	Domain
IPR017957	P_trefoil_CS	Conserved_site
IPR017994	P_trefoil_chordata	Family
IPR044913	P_trefoil_dom_sf	Homologous_superfamily

Pfam: PF00088

UniProt features (22 total): sequence variant 7, strand 6, disulfide bond 3, helix 2, signal peptide 1, chain 1, mutagenesis site 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6V1D	X-RAY DIFFRACTION	2.4
1HI7	SOLUTION NMR
1PS2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04155-F1	88.17	0.65

Functional residue map

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

Disulfide bonds (3): 31–57, 41–56, 51–68

Mutagenesis-validated functional residues (1):

Position	Phenotype
82	abolishes inhibition of gastric cancer cell growth.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-162582	Signal Transduction
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 131 (showing top): GOBP_DIGESTION, MODULE_92, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_IMMOBILIZATION_STRESS, XU_GH1_AUTOCRINE_TARGETS_UP, BECKER_TAMOXIFEN_RESISTANCE_UP, GOZGIT_ESR1_TARGETS_DN, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, GOMF_GROWTH_FACTOR_ACTIVITY, STOSSI_RESPONSE_TO_ESTRADIOL, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP, GOBP_RESPONSE_TO_METAL_ION, MODULE_75, DOANE_RESPONSE_TO_ANDROGEN_DN, SMID_BREAST_CANCER_LUMINAL_B_UP

GO Biological Process (9): carbohydrate metabolic process (GO:0005975), cell population proliferation (GO:0008283), negative regulation of cell population proliferation (GO:0008285), response to iron ion (GO:0010039), cell differentiation (GO:0030154), maintenance of gastrointestinal epithelium (GO:0030277), response to immobilization stress (GO:0035902), response to peptide hormone (GO:0043434), signal transduction (GO:0007165)

GO Molecular Function (2): growth factor activity (GO:0008083), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
ESR-mediated signaling	1
Signaling by Nuclear Receptors	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
primary metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to metal ion	1
cellular developmental process	1
epithelial structure maintenance	1
digestive system process	1
response to stress	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFF1	GREB1	Q4ZG55	882
TFF1	GKN2	Q86XP6	877
TFF1	ESR1	P03372	788
TFF1	PGR	P06401	757
TFF1	MUC5AC	P98088	729
TFF1	MUC6	Q6W4X9	726
TFF1	PDE9A	O76083	691
TFF1	FOXA1	P55317	674
TFF1	REG1A	P05451	607
TFF1	TFF3	Q07654	597
TFF1	REG1B	P48304	583
TFF1	XBP1	P17861	548
TFF1	NCOA3	Q9Y6Q9	548
TFF1	MUC2	Q02817	540
TFF1	FOXA3	P55318	529

IntAct

47 interactions, top by confidence:

A	B	Type	Score
TFF1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.670
TFF1	PIEZO1	psi-mi:“MI:0915”(physical association)	0.600
PIEZO1	TFF1	psi-mi:“MI:0915”(physical association)	0.600
TFF1	PIEZO1	psi-mi:“MI:0403”(colocalization)	0.600
TFF1	ZNF250	psi-mi:“MI:0915”(physical association)	0.560
ZNF250	TFF1	psi-mi:“MI:0915”(physical association)	0.560
TFF1	SGTB	psi-mi:“MI:0915”(physical association)	0.560
TFF1	VSNL1	psi-mi:“MI:0915”(physical association)	0.560
TFF1	BTN3A1	psi-mi:“MI:0915”(physical association)	0.540
BTNL8	TFF1	psi-mi:“MI:0915”(physical association)	0.540
CD300LD	TFF1	psi-mi:“MI:0915”(physical association)	0.540
TFF1	FCRL4	psi-mi:“MI:0915”(physical association)	0.540
SIGLEC8	TFF1	psi-mi:“MI:0915”(physical association)	0.540
TFF1	BTN3A1	psi-mi:“MI:0407”(direct interaction)	0.540
BTNL8	TFF1	psi-mi:“MI:0407”(direct interaction)	0.540
TFF1	CD300LD	psi-mi:“MI:0407”(direct interaction)	0.540
FCRL4	TFF1	psi-mi:“MI:0407”(direct interaction)	0.540
SIGLEC8	TFF1	psi-mi:“MI:0407”(direct interaction)	0.540
TFF1	FCRL4	psi-mi:“MI:0407”(direct interaction)	0.540
TFF1	BTNL8	psi-mi:“MI:0407”(direct interaction)	0.540
BTN3A1	TFF1	psi-mi:“MI:0407”(direct interaction)	0.540
AKT1	TFF1	psi-mi:“MI:0915”(physical association)	0.370
TFF1	APC	psi-mi:“MI:0915”(physical association)	0.370
ATM	TFF1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (30): ZNF250 (Two-hybrid), UBQLN1 (Two-hybrid), TFF1 (Two-hybrid), TFF1 (Two-hybrid), TFF1 (Two-hybrid), TFF1 (Two-hybrid), TFF1 (Two-hybrid), TFF1 (Two-hybrid), TFF1 (Two-hybrid), TFF1 (Two-hybrid), TFF1 (Two-hybrid), VSNL1 (Two-hybrid), SGTB (Two-hybrid), TFF1 (Affinity Capture-Western), TFF1 (Reconstituted Complex)

ESM2 similar proteins: A8YXX7, B4X8D9, O46655, O75711, O76095, O77049, O88745, O88823, O88824, P01186, P01359, P04155, P08163, P08833, P0CW02, P18406, P21743, P21744, P22934, P24593, P24594, P25118, P35455, P47876, P47879, P55773, Q03191, Q03403, Q05717, Q07079, Q07654, Q08423, Q16663, Q28985, Q29183, Q62395, Q63467, Q66IA6, Q6DGP8, Q6Q484

Diamond homologs: A8YXX7, B4X8D9, P01359, P04155, P10667, P17437, Q00222, Q00223, Q03191, Q03403, Q03404, Q05049, Q07654, Q08423, Q09030, Q29183, Q62395, Q63467, Q863B4, Q863J2, Q863T4, B3EWZ5, B3EWZ6, Q9MYM4, P10253, Q5R7A9

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
AIP	“down-regulates quantity by repression”	TFF1	“transcriptional regulation”
BRCA1	“down-regulates quantity by repression”	TFF1	“transcriptional regulation”
ESR1	“up-regulates quantity by expression”	TFF1	“transcriptional regulation”
ESR2	“up-regulates quantity by expression”	TFF1	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	TFF1	“transcriptional regulation”
NFATC3	“up-regulates quantity by expression”	TFF1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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.

GO biological processes:

GO term	Partners	Fold	FDR
DNA damage response	5	14.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

308 predictions. Top by Δscore:

Variant	Effect	Δscore
21:42362491:CTCCT:C	acceptor_gain	1.0000
21:42362496:C:CC	acceptor_gain	1.0000
21:42363249:CCATA:C	donor_loss	1.0000
21:42363250:CATAC:C	donor_loss	1.0000
21:42363251:ATAC:A	donor_loss	1.0000
21:42363252:TA:T	donor_loss	1.0000
21:42363253:A:AG	donor_loss	1.0000
21:42363254:CCTT:C	donor_gain	1.0000
21:42363403:CGTCT:C	acceptor_gain	1.0000
21:42363414:G:C	acceptor_gain	1.0000
21:42363414:G:GC	acceptor_gain	1.0000
21:42366405:CCTTA:C	donor_loss	1.0000
21:42366406:CTTA:C	donor_loss	1.0000
21:42366407:TTACC:T	donor_loss	1.0000
21:42366408:TACCT:T	donor_loss	1.0000
21:42366409:ACC:A	donor_loss	1.0000
21:42366410:CCTGT:C	donor_gain	1.0000
21:42362492:TCCT:T	acceptor_gain	0.9900
21:42362493:CCTC:C	acceptor_gain	0.9900
21:42362494:CT:C	acceptor_gain	0.9900
21:42362496:CT:C	acceptor_loss	0.9900
21:42362497:T:C	acceptor_loss	0.9900
21:42362504:G:C	acceptor_gain	0.9900
21:42362504:G:GC	acceptor_gain	0.9900
21:42363406:CT:C	acceptor_gain	0.9900
21:42363407:TC:T	acceptor_loss	0.9900
21:42363408:C:CA	acceptor_loss	0.9900
21:42363408:C:CC	acceptor_gain	0.9900
21:42363409:T:A	acceptor_loss	0.9900
21:42363417:C:CT	acceptor_gain	0.9900

AlphaMissense

546 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:42363286:G:C	F69L	0.998
21:42363286:G:T	F69L	0.998
21:42363288:A:G	F69L	0.998
21:42363319:G:C	F58L	0.998
21:42363319:G:T	F58L	0.998
21:42363321:A:G	F58L	0.998
21:42363320:A:C	F58C	0.997
21:42363290:C:G	C68S	0.996
21:42363291:A:T	C68S	0.996
21:42363379:T:A	R38S	0.996
21:42363379:T:G	R38S	0.996
21:42363287:A:C	F69C	0.995
21:42363292:C:A	W67C	0.995
21:42363292:C:G	W67C	0.995
21:42363341:C:G	C51S	0.995
21:42363342:A:T	C51S	0.995
21:42363371:C:G	C41S	0.995
21:42363372:A:T	C41S	0.995
21:42363326:C:G	C56S	0.993
21:42363327:A:T	C56S	0.993
21:42363380:C:G	R38T	0.993
21:42363291:A:G	C68R	0.991
21:42363323:C:G	C57S	0.991
21:42363324:A:T	C57S	0.991
21:42363371:C:T	C41Y	0.991
21:42363340:A:C	C51W	0.990
21:42363289:G:C	C68W	0.989
21:42363327:A:G	C56R	0.989
21:42363371:C:A	C41F	0.989
21:42363370:A:C	C41W	0.988

dbSNP variants (sampled 300 via entrez): RS1000411235 (21:42363045 A>G,T), RS1000749184 (21:42362031 C>T), RS1000936285 (21:42366192 C>A,T), RS1001677327 (21:42365251 C>T), RS1001730728 (21:42365443 C>T), RS1002207082 (21:42362287 A>T), RS1002280445 (21:42364362 G>A,C,T), RS1002350638 (21:42366659 A>C,G), RS1002790303 (21:42366891 A>G), RS1002811012 (21:42364456 G>A), RS1002947075 (21:42364232 G>A,T), RS1003179071 (21:42363354 T>C), RS1003343764 (21:42361943 C>T), RS1003384013 (21:42367924 C>T), RS1003562751 (21:42368494 C>A,T)

Disease associations

OMIM: gene MIM:113710 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001350_8	Pancreatic cancer	4.000000e-13
GCST006585_2315	Blood protein levels	6.000000e-42

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases reaction, affects binding, affects reaction, decreases expression, affects cotreatment (+4 more)	109
Fulvestrant	decreases reaction, increases expression, increases secretion, increases reaction, decreases expression (+1 more)	28
bisphenol A	decreases reaction, increases expression, affects cotreatment, decreases expression, increases activity (+3 more)	20
afimoxifene	affects binding, decreases reaction, increases expression, increases reaction, decreases expression	12
Tetrachlorodibenzodioxin	decreases secretion, increases expression, increases secretion, affects binding, decreases reaction (+3 more)	12
Tamoxifen	increases reaction, affects cotreatment, increases expression, decreases expression, affects binding (+1 more)	10
Genistein	decreases reaction, increases expression	8
Raloxifene Hydrochloride	affects binding, affects cotreatment, decreases expression, increases expression, decreases reaction	6
o,p’-DDT	decreases reaction, increases expression	5
butylparaben	increases expression, decreases reaction	5
Diethylstilbestrol	decreases reaction, increases expression	5
Resveratrol	increases expression, decreases expression	4
Coumestrol	affects reaction, decreases reaction, affects cotreatment, increases expression	4
Quercetin	increases expression, decreases reaction	4
kaempferol	decreases reaction, increases expression	3
trichostatin A	affects cotreatment, affects expression, increases expression, decreases expression, decreases reaction	3
beta-hexachlorocyclohexane	increases expression, decreases reaction	3
tetrachlorodian	decreases reaction, increases expression	3
ICI 164384	decreases reaction, increases expression	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	affects reaction, decreases reaction, increases expression, affects expression	3
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression	3
bisphenol AF	increases expression, decreases reaction, affects reaction	3
Benzo(a)pyrene	affects methylation, affects binding, increases reaction, increases expression, increases methylation	3
Progesterone	affects cotreatment, decreases expression, decreases reaction, increases expression, affects expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
daidzein	increases expression, decreases reaction	2
propylparaben	decreases reaction, increases expression	2
phenothrin	increases expression, decreases reaction	2
deoxynivalenol	affects reaction, decreases reaction, increases expression, increases reaction, decreases secretion (+1 more)	2
methylselenic acid	decreases reaction, increases expression	2

Clinical trials (associated diseases)

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