PAPSS1

Summary

PAPSS1 (3’-phosphoadenosine 5’-phosphosulfate synthase 1, HGNC:8603) is a protein-coding gene on chromosome 4q25, encoding Bifunctional 3’-phosphoadenosine 5’-phosphosulfate synthase 1 (O43252). Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway.

Three-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS) is the sulfate donor cosubstrate for all sulfotransferase (SULT) enzymes (Xu et al., 2000 [PubMed 10679223]). SULTs catalyze the sulfate conjugation of many endogenous and exogenous compounds, including drugs and other xenobiotics. In humans, PAPS is synthesized from adenosine 5-prime triphosphate (ATP) and inorganic sulfate by 2 isoforms, PAPSS1 and PAPSS2 (MIM 603005).

Source: NCBI Gene 9061 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 91 total
• Druggable target: yes
• MANE Select transcript: NM_005443

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8603
Approved symbol	PAPSS1
Name	3’-phosphoadenosine 5’-phosphosulfate synthase 1
Location	4q25
Locus type	gene with protein product
Status	Approved
Aliases	ATPSK1, PAPSS
Ensembl gene	ENSG00000138801
Ensembl biotype	protein_coding
OMIM	603262
Entrez	9061

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 6 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000265174, ENST00000502431, ENST00000504987, ENST00000506544, ENST00000511304, ENST00000512641, ENST00000514489, ENST00000514815, ENST00000873396, ENST00000931559, ENST00000931560, ENST00000931561, ENST00000931562, ENST00000931563, ENST00000970503, ENST00000970504, ENST00000970505

RefSeq mRNA: 1 — MANE Select: NM_005443 NM_005443

CCDS: CCDS3676

Canonical transcript exons

ENST00000265174 — 12 exons

Exon	Start	End
ENSE00000935008	107720120	107720234
ENSE00001217412	107631631	107631860
ENSE00001217417	107644802	107645070
ENSE00001217423	107653491	107653626
ENSE00001217468	107613666	107614387
ENSE00003471924	107654695	107654900
ENSE00003479166	107656896	107657007
ENSE00003507113	107701171	107701285
ENSE00003557775	107693771	107694006
ENSE00003600794	107659959	107660072
ENSE00003690972	107682015	107682133
ENSE00003692919	107687039	107687177

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.1224 / max 839.5309, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53505	46.4919	1818
53504	0.6305	347

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	98.75	gold quality
secondary oocyte	CL:0000655	98.57	gold quality
pons	UBERON:0000988	98.56	gold quality
bronchial epithelial cell	CL:0002328	98.42	gold quality
subthalamic nucleus	UBERON:0001906	98.36	gold quality
pylorus	UBERON:0001166	98.32	gold quality
corpus callosum	UBERON:0002336	98.23	gold quality
endometrium	UBERON:0001295	98.15	gold quality
superior vestibular nucleus	UBERON:0007227	98.05	gold quality
medulla oblongata	UBERON:0001896	97.93	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.91	gold quality
epithelium of bronchus	UBERON:0002031	97.87	gold quality
bronchus	UBERON:0002185	97.85	gold quality
trigeminal ganglion	UBERON:0001675	97.69	gold quality
spinal cord	UBERON:0002240	97.63	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.62	gold quality
tibia	UBERON:0000979	97.61	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.54	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.51	gold quality
trachea	UBERON:0003126	97.50	gold quality
lower lobe of lung	UBERON:0008949	97.41	gold quality
lateral globus pallidus	UBERON:0002476	97.38	gold quality
cardia of stomach	UBERON:0001162	97.37	gold quality
dorsal root ganglion	UBERON:0000044	97.32	gold quality
orbitofrontal cortex	UBERON:0004167	97.31	gold quality
cortical plate	UBERON:0005343	97.31	gold quality
hair follicle	UBERON:0002073	97.29	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.24	gold quality
mammary duct	UBERON:0001765	97.23	gold quality
nipple	UBERON:0002030	97.14	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	49.70
E-HCAD-13	yes	13.47
E-MTAB-9801	yes	4.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP2, SP3

miRNA regulators (miRDB)

56 targeting PAPSS1, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-1287-3P	99.63	66.93	492

Literature-anchored findings (GeneRIF, showing 18)

• characterization and expression of bifunctional isoforms (PMID:11931637)
• review of PAPSS biochemistry, molecular biology and genetics (PMID:12716056)
• x-ray crystallographic analysis of 3’-phosphoadenosine-5’-phosphosulfate synthetase 1 (PMID:14747722)
• The kinetic characteristics of the individual sulfurylase and kinase activities of PAPSS isoform 1, the predominant form in human brain, are described. (PMID:15065880)
• Results describe the crystal structure of human PAPSS1 at 1.8 angstroms resolution. (PMID:15755455)
• ATP-sulfurylase domain of PAPS synthetase influences these elements in adenylylsulfate kinase, which may be a mechanism between both domains the this bifunctional enzyme (PMID:17540769)
• a role for PAPSS1 in the cellular sulfonation pathway requirement at a stage during or shortly after MLV provirus establishment, and subsequent influence on gene expression from the viral long terminal repeat promoter (PMID:19008949)
• PAPSS1 maps to chromosome 4q25 and may havea role in hepatocellular carcinoma (PMID:19337310)
• SK1 plays an essential role in regulating in vitro paracrine angiogenesis and lymphangiogenesis. (PMID:20335228)
• Unusual localisation signals of both PAPS synthase isoforms, are described. (PMID:22242175)
• study showed expression patterns of SULT1E1 and PAPSS in breast and endometrial tissues; the estrogen sulfation enzymes were comparatively higher in the tumorous tissues than adjacent normal tissues; overexpression of SULT1E1 and PAPSS1 retarded MCF-7 cells growth in vivo and in vitro by arresting cell cycles and inducing apoptosis (PMID:22380844)
• SK1 positivity and high expression were significantly associated with cancer and a shorter 5-year and overall survival. (PMID:24587339)
• leptin signalling links a novel SFK/ERK1/2-mediated pathway and SK1 expression. (PMID:25482303)
• These data indicate that knocking down PAPSS increases UGT2B4 transcription and mRNA stability as a compensatory response to the loss of SULT2A1 activity (PMID:25948711)
• we found that ectopic expression of oncogenic KRas and HRas in cells resulted in elevated CIB1 expression. We previously described the Ca(2+)-myristoyl switch function of CIB1, and its ability to facilitate agonist-induced plasma membrane localisation of sphingosine kinase 1 (SK1), a location where SK1 is known to elicit oncogenic signalling. (PMID:27941888)
• These results suggest that PAPSS1 inhibition enhances cisplatin activity in multiple preclinical model systems and that low PAPSS1 expression may serve as a biomarker for platin sensitivity in cancer patients. Developing strategies to target PAPSS1 activity in conjunction with platinum-based chemotherapy may offer an approach to improving treatment outcomes (PMID:28790117)
• Correlation of 3’-phosphoadenosine-5’-phosphosulfate synthase 1 (PAPSS1) expression with clinical parameters and prognosis in esophageal squamous cell carcinoma. (PMID:36734141)
• The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells. (PMID:37684671)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	papss1	ENSDARG00000057099
mus_musculus	Papss1	ENSMUSG00000028032
rattus_norvegicus	Papss1	ENSRNOG00000011311
drosophila_melanogaster	Papss	FBGN0020389
caenorhabditis_elegans		WBGENE00004091

Paralogs (1): PAPSS2 (ENSG00000198682)

Protein

Protein identifiers

Bifunctional 3’-phosphoadenosine 5’-phosphosulfate synthase 1 — O43252 (reviewed: O43252)

Alternative names: Sulfurylase kinase 1

All UniProt accessions (1): O43252

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5’-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3’-phosphoadenylylsulfate (PAPS: activated sulfate donor used by sulfotransferase). In mammals, PAPS is the sole source of sulfate; APS appears to be only an intermediate in the sulfate-activation pathway. Required for normal biosynthesis of sulfated L-selectin ligands in endothelial cells.

Subunit / interactions. Homodimer.

Tissue specificity. Expressed in testis, pancreas, kidney, thymus, prostate, ovary, small intestine, colon, leukocytes and liver. Also expressed in high endothelial venules (HEV) cells and in cartilage.

Activity regulation. Inhibited by chlorate. The kinase activity is subject to inhibition by the substrate adenylyl sulfate.

Domain organisation. The N-terminal first 50 residues are required for inhibition by the substrate adenylyl sulfate.

Pathway. Sulfur metabolism; sulfate assimilation.

Similarity. In the N-terminal section; belongs to the APS kinase family. In the C-terminal section; belongs to the sulfate adenylyltransferase family.

RefSeq proteins (1): NP_005434* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002650	Sulphate_adenylyltransferase	Family
IPR002891	APS	Family
IPR014729	Rossmann-like_a/b/a_fold	Homologous_superfamily
IPR015947	PUA-like_sf	Homologous_superfamily
IPR024951	Sulfurylase_cat_dom	Domain
IPR025980	ATP-Sase_PUA-like_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR059117	APS_kinase_dom	Domain

Pfam: PF01583, PF01747, PF14306

Enzyme classification (BRENDA):

• EC 2.7.1.25 — adenylyl-sulfate kinase (BRENDA: 29 organisms, 42 substrates, 74 inhibitors, 68 Km, 23 kcat entries)
• EC 2.7.7.4 — sulfate adenylyltransferase (BRENDA: 80 organisms, 68 substrates, 98 inhibitors, 191 Km, 23 kcat entries)

Substrate kinetics (BRENDA)

23 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0077–2.6	62
DIPHOSPHATE	0.0007–19.41	41
ADENOSINE 5’-PHOSPHOSULFATE	0.0001–0.042	29
ATP	0.007–2.4	22
ADENYLYL SULFATE	0.0044–2.95	21
SO42-	0.18–3.3	16
ADENOSINE 5’-PHOSPHOSULFATE	0.0003–0.17	11
MOO42-	0.076–0.64	11
SULFATE	0.0021–17	7
3’-PHOSPHOADENOSINE 5’-PHOSPHOSULFATE	0.003–0.37	5
ADENYLYL SULFATE	0.002–0.0046	5
ADENYLYLSULFATE	0.0004–0.025	4
MGATP2-	0.23–1.1	3
SEO42-	0.1–1	3
ADENOSINE-5’-PHOSPHOSULFATE	0.0004–0.0007	2

Catalyzed reactions (Rhea), 2 shown:

• sulfate + ATP + H(+) = adenosine 5’-phosphosulfate + diphosphate (RHEA:18133)
• adenosine 5’-phosphosulfate + ATP = 3’-phosphoadenylyl sulfate + ADP + H(+) (RHEA:24152)

UniProt features (81 total): helix 25, strand 21, binding site 12, mutagenesis site 7, turn 6, sequence conflict 3, region of interest 2, modified residue 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
2PEZ	X-RAY DIFFRACTION	1.4
8I1M	X-RAY DIFFRACTION	1.7
1X6V	X-RAY DIFFRACTION	1.75
2PEY	X-RAY DIFFRACTION	1.88
2OFX	X-RAY DIFFRACTION	1.9
1XNJ	X-RAY DIFFRACTION	1.98
2OFW	X-RAY DIFFRACTION	2.05
1XJQ	X-RAY DIFFRACTION	2.06
2QJF	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43252-F1	93.66	0.88

Functional residue map

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

Ligand- & substrate-binding residues (12): 207; 212; 419–422; 521–525; 563; 62–67; 89–92; 101; 106–109; 132–133; 171; 184–185

Post-translational modifications (2): 1, 12

Mutagenesis-validated functional residues (7):

Position	Phenotype
37	abolishes inhibition by the substrate adenylyl sulfate.
40	abolishes inhibition by the substrate adenylyl sulfate.
425	loss of activity.
426	increased activity.
427–428	loss of activity.
427	30% decrease in activity.
428	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-174362	Transport and metabolism of PAPS
R-HSA-2408550	Metabolism of ingested H2SeO4 and H2SeO3 into H2Se
R-HSA-6802952	Signaling by BRAF and RAF1 fusions

MSigDB gene sets: 220 (showing top): GGGACCA_MIR133A_MIR133B, chr4q25, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_HDAC1, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MORF_HDAC2, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, DOANE_BREAST_CANCER_CLASSES_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, MORF_RAB6A

GO Biological Process (3): sulfate assimilation (GO:0000103), skeletal system development (GO:0001501), 3’-phosphoadenosine 5’-phosphosulfate biosynthetic process (GO:0050428)

GO Molecular Function (10): adenylylsulfate kinase activity (GO:0004020), sulfate adenylyltransferase (ATP) activity (GO:0004781), ATP binding (GO:0005524), nucleotidyltransferase activity (GO:0016779), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glycosaminoglycan metabolism	1
Selenoamino acid metabolism	1
Oncogenic MAPK signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transferase activity, transferring phosphorus-containing groups	2
cellular anatomical structure	2
sulfur compound metabolic process	1
system development	1
purine ribonucleotide biosynthetic process	1
purine ribonucleoside bisphosphate biosynthetic process	1
sulfur compound biosynthetic process	1
3’-phosphoadenosine 5’-phosphosulfate metabolic process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
sulfate adenylyltransferase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1890 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAPSS1	SLC26A2	P50443	918
PAPSS1	SULT1B1	O43704	837
PAPSS1	SULT1C4	O75897	829
PAPSS1	SULT1C3	Q6IMI6	818
PAPSS1	ENTPD3	O75355	702
PAPSS1	ENTPD8	Q5MY95	702
PAPSS1	ENTPD1	P49961	608
PAPSS1	SULT2A1	Q06520	576
PAPSS1	TPST2	O60704	555
PAPSS1	TST	Q16762	531
PAPSS1	PPA2	Q9H2U2	530
PAPSS1	BPNT2	Q9NX62	528
PAPSS1	SLC35B2	Q8TB61	522
PAPSS1	SELL	P14151	520
PAPSS1	PPA1	Q15181	506

IntAct

64 interactions, top by confidence:

A	B	Type	Score
FANCG	FANCA	psi-mi:“MI:0914”(association)	0.960
DYNC1I2	DYNC1LI2	psi-mi:“MI:0914”(association)	0.680
GPX7	GAK	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
WDCP	PAPSS1	psi-mi:“MI:0914”(association)	0.530
MCRIP2	CASC3	psi-mi:“MI:0914”(association)	0.530
Papss1	PAPSS1	psi-mi:“MI:0915”(physical association)	0.400
PAPSS2	PAPSS1	psi-mi:“MI:0915”(physical association)	0.400
PAPSS1	PAPSS2	psi-mi:“MI:0915”(physical association)	0.400
Ppp2r1a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Rhoa	CLK2	psi-mi:“MI:0914”(association)	0.350
TMEM132A	WWP2	psi-mi:“MI:0914”(association)	0.350
NCK1	APBB2	psi-mi:“MI:0914”(association)	0.350
RNASEH2A	PHF20L1	psi-mi:“MI:0914”(association)	0.350
FANCI	FAAP20	psi-mi:“MI:0914”(association)	0.350
Tyw3	PPP6C	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
FGB	NME2	psi-mi:“MI:0914”(association)	0.350
DYNC1I2	DYNC1LI2	psi-mi:“MI:0914”(association)	0.350

BioGRID (107): PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Two-hybrid), PAPSS2 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS), PAPSS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A061AE05, A1CJC1, A1D858, A5CXS6, A5WEH0, A9A541, B0JW81, B1XLP7, B2J5M3, B4SAM9, B7JVS6, O43252, O54820, O88428, O95340, P08536, P0CN04, P0CN05, P56862, P78937, P94281, Q0CC19, Q0V6P9, Q0VRM0, Q111K4, Q12555, Q12650, Q1EAF9, Q1QAY1, Q27128, Q2H454, Q3AQ83, Q4FST7, Q4I1N3, Q4P460, Q4WWN8, Q60967, Q60FC6, Q6BSU5, Q6CFD2

Diamond homologs: A0A061AE05, A0KTI5, A1AEU4, A1RGG0, A1S9N4, A1U3X8, A3D819, A4WDV5, A4Y9X0, A5G863, A5N960, A6TD42, A6WJU6, A7MJ70, A7ZQJ4, A8A3M9, A8ANW4, A8H0A6, A9ENT2, A9G7W0, A9L392, A9MF25, A9N2D7, B0CAX3, B0TTD2, B1IUS9, B1LQ71, B1XCS6, B2TZI1, B2VG00, B4T460, B4TFX0, B4TTW4, B5BEY7, B5F414, B5FTS8, B5QW21, B5RDQ6, B5XV31, B5Z3B2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2211 predictions. Top by Δscore:

Variant	Effect	Δscore
4:107614385:TGG:T	acceptor_gain	1.0000
4:107614386:GG:G	acceptor_gain	1.0000
4:107614388:C:CC	acceptor_gain	1.0000
4:107631624:GACTT:G	donor_loss	1.0000
4:107631625:ACTTA:A	donor_loss	1.0000
4:107631627:TTAC:T	donor_loss	1.0000
4:107631628:TACTG:T	donor_loss	1.0000
4:107631629:A:AC	donor_gain	1.0000
4:107631629:ACTG:A	donor_loss	1.0000
4:107631630:C:CG	donor_gain	1.0000
4:107631630:CT:C	donor_gain	1.0000
4:107631630:CTG:C	donor_gain	1.0000
4:107631630:CTGT:C	donor_gain	1.0000
4:107631630:CTGTT:C	donor_gain	1.0000
4:107631856:TGGAC:T	acceptor_gain	1.0000
4:107631861:C:CC	acceptor_gain	1.0000
4:107631861:CTAG:C	acceptor_loss	1.0000
4:107645067:GCAT:G	acceptor_gain	1.0000
4:107645068:CAT:C	acceptor_gain	1.0000
4:107645068:CATC:C	acceptor_gain	1.0000
4:107645070:TCTGA:T	acceptor_loss	1.0000
4:107645071:C:CC	acceptor_gain	1.0000
4:107645071:C:T	acceptor_loss	1.0000
4:107645072:T:C	acceptor_loss	1.0000
4:107653622:ACCAT:A	acceptor_gain	1.0000
4:107653623:CCAT:C	acceptor_gain	1.0000
4:107653623:CCATC:C	acceptor_gain	1.0000
4:107653624:CAT:C	acceptor_gain	1.0000
4:107653624:CATC:C	acceptor_gain	1.0000
4:107653625:AT:A	acceptor_gain	1.0000

AlphaMissense

4113 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:107614350:G:T	R592S	1.000
4:107631687:A:C	F560L	1.000
4:107631687:A:T	F560L	1.000
4:107631689:A:G	F560L	1.000
4:107631793:G:T	A525D	1.000
4:107631805:C:T	G521E	1.000
4:107631846:G:C	C507W	1.000
4:107631854:A:G	W505R	1.000
4:107631854:A:T	W505R	1.000
4:107644812:C:T	G499E	1.000
4:107645035:G:C	H425D	1.000
4:107645042:G:C	N422K	1.000
4:107645042:G:T	N422K	1.000
4:107645054:A:C	F418L	1.000
4:107645054:A:T	F418L	1.000
4:107645056:A:G	F418L	1.000
4:107653520:A:G	L403P	1.000
4:107656971:A:G	W274R	1.000
4:107656971:A:T	W274R	1.000
4:107682129:G:C	F185L	1.000
4:107682129:G:T	F185L	1.000
4:107682130:A:G	F185S	1.000
4:107682131:A:G	F185L	1.000
4:107687173:C:G	R139P	1.000
4:107693787:A:T	I132K	1.000
4:107693792:A:C	S130R	1.000
4:107693792:A:T	S130R	1.000
4:107693794:T:G	S130R	1.000
4:107693833:C:G	A117P	1.000
4:107693847:C:G	R112P	1.000

dbSNP variants (sampled 300 via entrez): RS1000007506 (4:107711134 G>C), RS1000016999 (4:107640898 T>A,C), RS1000044883 (4:107624279 G>A,T), RS1000047757 (4:107666484 A>G), RS1000079861 (4:107695247 T>C), RS1000080725 (4:107675264 T>C), RS1000102074 (4:107710914 A>G), RS1000130827 (4:107618192 G>T), RS1000156541 (4:107717418 G>A), RS1000158995 (4:107665897 T>C), RS1000194001 (4:107705483 T>C), RS1000201358 (4:107659705 A>T), RS1000213560 (4:107705400 T>C,G), RS1000217480 (4:107655401 A>T), RS10002310 (4:107684653 C>G,T)

Disease associations

OMIM: gene MIM:603262 | 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
GCST002336_3	Telomere length	5.000000e-08
GCST004735_4	Epstein-Barr virus copy number in lymphoblastoid cell lines	1.000000e-06
GCST009614_1	LDL cholesterol levels x loop diuretics use interaction	2.000000e-07
GCST009614_4	LDL cholesterol levels x loop diuretics use interaction	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067042 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation, affects expression	4
arsenite	increases methylation, affects binding, decreases reaction	2
sodium arsenite	decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	decreases expression, increases abundance	2
Lead	affects methylation, decreases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
glycidyl methacrylate	increases expression	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
afimoxifene	decreases response to substance	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
arsenic acid	affects binding, affects metabolic processing	1
potassium chromate(VI)	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
diisodecyl phthalate	decreases expression	1
molybdate	affects binding, affects metabolic processing	1
tungstate	affects binding, affects metabolic processing	1
di-n-butylphosphoric acid	affects expression	1
1-hydroxymethylpyrene	affects cotreatment, increases activity	1
4-octylphenol	decreases expression	1
azoxystrobin	increases expression	1
K 7174	decreases expression	1
nutlin 3	increases secretion, affects cotreatment, increases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651978	Binding	Binding affinity to human PAPSS1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2G2	HAP1 PAPSS1 (-) 1	Cancer cell line	Male
CVCL_E2G3	HAP1 PAPSS1 (-) 2	Cancer cell line	Male
CVCL_E2G4	HAP1 PAPSS1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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