S100A10

Summary

S100A10 (S100 calcium binding protein A10, HGNC:10487) is a protein-coding gene on chromosome 1q21.3, encoding Protein S100-A10 (P60903). Because S100A10 induces the dimerization of ANXA2/p36, it may function as a regulator of protein phosphorylation in that the ANXA2 monomer is the preferred target (in vitro) of tyrosine-specific kinase.

The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in exocytosis and endocytosis.

Source: NCBI Gene 6281 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 10 total
• Druggable target: yes
• MANE Select transcript: NM_002966

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10487
Approved symbol	S100A10
Name	S100 calcium binding protein A10
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	P11, 42C, CLP11
Ensembl gene	ENSG00000197747
Ensembl biotype	protein_coding
OMIM	114085
Entrez	6281

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000368809, ENST00000368811, ENST00000478348, ENST00000478574, ENST00000872056, ENST00000872057, ENST00000919940, ENST00000919941, ENST00000919942, ENST00000919943

RefSeq mRNA: 1 — MANE Select: NM_002966 NM_002966

CCDS: CCDS1008

Canonical transcript exons

ENST00000368811 — 3 exons

Exon	Start	End
ENSE00001148206	151982915	151983324
ENSE00001448013	151993752	151993859
ENSE00003509339	151986099	151986251

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 564.0447 / max 3479.0879, expressed in 1784 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14507	561.8200	1784
14501	0.6567	136
14496	0.5915	321
14503	0.3739	155
14504	0.2029	97
14505	0.1423	88
14506	0.0746	20
14499	0.0708	40
14502	0.0681	34
14500	0.0438	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	99.94	gold quality
colonic mucosa	UBERON:0000317	99.93	gold quality
dorsal root ganglion	UBERON:0000044	99.90	gold quality
synovial joint	UBERON:0002217	99.86	gold quality
germinal epithelium of ovary	UBERON:0001304	99.85	gold quality
endometrium epithelium	UBERON:0004811	99.85	gold quality
tongue squamous epithelium	UBERON:0006919	99.85	gold quality
lower esophagus mucosa	UBERON:0035834	99.85	gold quality
pharyngeal mucosa	UBERON:0000355	99.84	gold quality
cartilage tissue	UBERON:0002418	99.84	gold quality
layer of synovial tissue	UBERON:0007616	99.84	gold quality
trigeminal ganglion	UBERON:0001675	99.82	gold quality
oral cavity	UBERON:0000167	99.81	gold quality
amniotic fluid	UBERON:0000173	99.81	gold quality
gingival epithelium	UBERON:0001949	99.79	gold quality
gingiva	UBERON:0001828	99.78	gold quality
esophagus mucosa	UBERON:0002469	99.77	gold quality
olfactory bulb	UBERON:0002264	99.76	gold quality
mucosa of transverse colon	UBERON:0004991	99.74	gold quality
lower lobe of lung	UBERON:0008949	99.74	gold quality
ileal mucosa	UBERON:0000331	99.73	gold quality
jejunal mucosa	UBERON:0000399	99.73	gold quality
mammalian vulva	UBERON:0000997	99.73	gold quality
pericardium	UBERON:0002407	99.73	gold quality
rectum	UBERON:0001052	99.72	gold quality
epithelium of esophagus	UBERON:0001976	99.71	gold quality
squamous epithelium	UBERON:0006914	99.71	gold quality
skin of hip	UBERON:0001554	99.70	gold quality
esophagus squamous epithelium	UBERON:0006920	99.69	gold quality
adult organism	UBERON:0007023	99.65	gold quality

Single-cell (SCXA)

Detected in 68 experiment(s), a significant marker in 48.

Experiment	Marker?	Max mean expression
E-MTAB-8207	yes	5231.09
E-HCAD-24	yes	5009.18
E-MTAB-7407	yes	4135.99
E-CURD-112	yes	3784.53
E-MTAB-9388	yes	3384.17
E-MTAB-8060	yes	3138.07
E-MTAB-9906	yes	3041.89
E-CURD-98	yes	2924.03
E-MTAB-10042	yes	2656.82
E-MTAB-8381	yes	2575.10
E-MTAB-10432	yes	2440.69
E-MTAB-6108	yes	2405.23
E-MTAB-10485	yes	2382.79
E-GEOD-81547	yes	2177.47
E-HCAD-8	yes	1801.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IFNG, JUN, NR3C1, RBPJ, SP1, STAT1, WT1

miRNA regulators (miRDB)

31 targeting S100A10, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-1302	97.92	67.27	844
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-4298	97.26	66.59	765
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-1226-5P	96.50	65.28	643
HSA-MIR-6847-3P	96.50	67.30	582
HSA-MIR-6834-5P	96.25	64.88	823
HSA-MIR-6828-3P	96.06	67.61	1155
HSA-MIR-4774-5P	95.92	68.27	827

Literature-anchored findings (GeneRIF, showing 40)

• These results suggest that epidermal growth factor treatment increased p11 bound to cPLA(2) may lead to the late suppression of AA release induced by EGF. (PMID:12163506)
• p11 interacts specifically with the TASK-1 K+ channel. (PMID:12198146)
• Calpactin light chain binds to bluetongue virus NS3 protein (PMID:12235365)
• IFN-gamma-stimulated p11 expression may serve a counterregulatory role in human epithelial cells (PMID:12645529)
• analysis of S100A10 interaction with tissue plasminogen activator, plasminogen, and plasmin (PMID:12730231)
• annexin 2/S100A10 complex functions in the intracellular positioning of recycling endosomes and that both subunits are required for this activity (PMID:13679511)
• Temperature stress-induced annexin 2 translocation is dependent on both expression of protein p11 tyrosine phosphorylation of annexin 2 (PMID:15302870)
• S100A10 and annexin A2 play an important role in plasmin regulation and in cancer cell invasiveness and metastasis [review] (PMID:15574370)
• complex with annexin II is a substrate of thioredoxin (PMID:15849182)
• analysis of the structural determinant of the PtdIns(4,5)P2 selectivity of A2t (annexin II-p11 heterotetramer), which may be involved in the regulation of PtdIns(4,5)P2 clustering in the cell (PMID:16230353)
• results of the present study indicate that the dynamic modulation of 5-HT1B receptor function by p11 may be involved in molecular adaptations occurring in neuronal networks that are dysfunctional in depression-like states (PMID:16400147)
• It is proposed that p11 may act through the tPA/plasminogen/BDNF pathway to achieve its antidepressant effect. (PMID:16890384)
• that Annexin2 is required for strong binding of S100A10 to the C-terminal domain of the protein Ahnak. (PMID:16984913)
• p11 expression was increased in inflammatory bowel disease (PMID:17241856)
• Single nucleotide polymorphisms in S100A10 gene is not associated with major depressive disorder (PMID:17510952)
• The anx 2-S100A10/CFTR complex is important for CFTR function across epithelia. (PMID:17581860)
• S100A10 and annexin II contribute to the aggressive characteristics of anaplastic carcinoma, while playing a constitutive role in papillary carcinoma. (PMID:17695432)
• analysis of the pH-induced membrane binding of annexins A6 and A2-S100A10 (PMID:17824845)
• p11/S100A10 light chain of annexin A2 is dispensable for annexin A2 association to endosomes and functions in endosomal transport (PMID:17971878)
• the annexin II-S100A10 complex, which regulates exocytosis, forms a ternary complex with TrpRS. (PMID:17999956)
• Within the endothelial cell, p11 is required for Src kinase-mediated tyrosine phosphorylation of A2, which signals translocation of both proteins to the cell surface. (PMID:18434302)
• Our findings suggest that p11 genetic variants do not play a major role in the MDD susceptibility, antidepressant therapeutic response or the risk of suicide attempt in MDD. (PMID:18838110)
• Expression of S100A10 (but not other S100 proteins investigated) varied in melanoma cell lines (i.e., S100A10 was down-regulated in 3 cell lines compared with normal melanocytes). Expression of S100A10 correlated with proliferation marker, Ki67. (PMID:19521263)
• CFTR function by annexin A2-S100A10 complex has roles in health and disease [review] (PMID:20093721)
• First insights of S100A10 function as a regulator of the filamentous actin network. (PMID:20100475)
• The results of this study suggested that PBMC p11 mRNA levels may be a potential adjunctive biomarker for the assessment of suicide risk in mental disorders and warrants a larger translational study to determine its clinical utility. (PMID:20863517)
• The present study represents a first attempt to systematically understand the molecular basis for the calcium-insensitive open conformation of S100A10. (PMID:21269277)
• S100A10 plays a crucial role in the generation of plasmin leading to fibrinolysis, thus providing a link to the clinical hemorrhagic phenotype of acute promyelocytic leukemia (PMID:21310922)
• Understanding the chromatin remodeling involved in the glucocorticoid-mediated increase of p11 expression by stress may clarify stress-induced over-expression of p (PMID:21367534)
• DLC1 binding to S100A10 did not affect DLC1’s RhoGAP activity, but it decreased the steady-state level of S100A10 expression. (PMID:21372205)
• This study demonstrates that PBMC p11 mRNA expression is associated with neural activation in the brain of BD patients and warrants a larger translational study to determine its clinical utility. (PMID:21722919)
• Both the annexin A2 and p11 subunits of calpactin I coimmunoprecipitate with human papillomavirus type 16 E5 in COS cells and in human epithelial cell lines, and an intact E5 C terminus is required for binding. (PMID:21849434)
• Interferon-gamma stimulates p11-dependent surface expression of annexin A2 in lung epithelial cells to enhance phagocytosis. (PMID:21928315)
• the overexpression of thioredoxin,S100-A10 and S100-A6 specifically distinguished metastatic from non-metastatic tumors. (PMID:21938494)
• COX7A2, TAGLN2 and S100-A10 as novel prognostic markers in Barrett’s adenocarcinoma. (PMID:22365974)
• Human chondrocytes with downregulated S100A10 showed significantly decreased production of inflammatory cytokines such as tumor necrosis factor-alpha, IL-1beta and IL-10; hence, S100A10 might be considered a potential target for anti-inflammatory treatment (PMID:22797859)
• Annexin A2 anchors S100A10 to the cell surface and, in doing so, allows S100A10 to play a prominent role in the activation of plasminogen in angiogenesis and oncogenesis. (PMID:22830395)
• annexin A2 heterotetramer contributes to HPV16 internalization and infection of epithelial cells and this interaction is dependent on the presence of the L2 minor capsid protein (PMID:22927980)
• The AHNAK peptide adopts a coil conformation that arches across the heterotetramer contacting both annexin A2 and S100A10 protomers with tight affinity. (PMID:22940583)
• N-terminal acetylation of AnxA2 is required for S100A10 binding (PMID:23091277)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	s100t	ENSDARG00000055589
mus_musculus	S100a10	ENSMUSG00000041959
rattus_norvegicus	S100a10	ENSRNOG00000023226

Paralogs (21): CRNN (ENSG00000143536), S100A8 (ENSG00000143546), S100A7 (ENSG00000143556), S100B (ENSG00000160307), S100A1 (ENSG00000160678), S100A11 (ENSG00000163191), S100A9 (ENSG00000163220), S100A12 (ENSG00000163221), S100P (ENSG00000163993), S100G (ENSG00000169906), S100Z (ENSG00000171643), S100A7A (ENSG00000184330), S100A3 (ENSG00000188015), S100A16 (ENSG00000188643), SNTN (ENSG00000188817), S100A13 (ENSG00000189171), S100A14 (ENSG00000189334), S100A4 (ENSG00000196154), S100A5 (ENSG00000196420), S100A2 (ENSG00000196754), S100A6 (ENSG00000197956)

Protein

Protein identifiers

Protein S100-A10 — P60903 (reviewed: P60903)

Alternative names: Calpactin I light chain, Calpactin-1 light chain, Cellular ligand of annexin II, S100 calcium-binding protein A10, p10 protein, p11

All UniProt accessions (1): P60903

UniProt curated annotations — full annotation on UniProt →

Function. Because S100A10 induces the dimerization of ANXA2/p36, it may function as a regulator of protein phosphorylation in that the ANXA2 monomer is the preferred target (in vitro) of tyrosine-specific kinase.

Subunit / interactions. Heterotetramer containing 2 light chains of S100A10/p11 and 2 heavy chains of ANXA2/p36. Interacts with SCN10A. Interacts with TASOR.

Miscellaneous. Does not appear to bind calcium. Contains 2 ancestral calcium site related to EF-hand domains that have lost their ability to bind calcium.

Similarity. Belongs to the S-100 family.

RefSeq proteins (1): NP_002957* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001751	S100/CaBP7/8-like_CS	Conserved_site
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR013787	S100_Ca-bd_sub	Domain
IPR028476	S100-A10	Family

Pfam: PF01023

UniProt features (17 total): helix 6, modified residue 5, strand 3, chain 1, region of interest 1, cross-link 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4HRG	X-RAY DIFFRACTION	2
1A4P	X-RAY DIFFRACTION	2.25
1BT6	X-RAY DIFFRACTION	2.4
4FTG	X-RAY DIFFRACTION	2.51
4HRE	X-RAY DIFFRACTION	2.79
4HRH	X-RAY DIFFRACTION	3
4DRW	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60903-F1	91.85	0.85

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 (6): 23, 28, 37, 54, 57, 37

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-75205	Dissolution of Fibrin Clot
R-HSA-109582	Hemostasis

MSigDB gene sets: 509 (showing top): GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, CREL_01, HONMA_DOCETAXEL_RESISTANCE, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_MEMBRANE_BIOGENESIS, GOBP_VESICLE_ORGANIZATION, GOBP_FOCAL_ADHESION_ASSEMBLY, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_EXOCYTOSIS, GOCC_CELL_SURFACE, HSIAO_HOUSEKEEPING_GENES, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP

GO Biological Process (13): membrane raft assembly (GO:0001765), vesicle budding from membrane (GO:0006900), positive regulation of plasminogen activation (GO:0010756), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of GTPase activity (GO:0043547), positive regulation of exocytosis (GO:0045921), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of neurogenesis (GO:0050767), positive regulation of stress fiber assembly (GO:0051496), positive regulation of focal adhesion assembly (GO:0051894), protein localization to plasma membrane (GO:0072659), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), positive regulation of plasma membrane repair (GO:1905686)

GO Molecular Function (5): calcium ion binding (GO:0005509), protein homodimerization activity (GO:0042803), transmembrane transporter binding (GO:0044325), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515)

GO Cellular Component (11): extracellular region (GO:0005576), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), nuclear matrix (GO:0016363), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), RNA polymerase II transcription regulator complex (GO:0090575), plasma membrane protein complex (GO:0098797), AnxA2-p11 complex (GO:1990665), membrane raft (GO:0045121)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transcription by RNA polymerase II	2
protein binding	2
membrane raft organization	1
membrane assembly	1
vesicle organization	1
vesicle-mediated transport	1
membrane organization	1
regulation of plasminogen activation	1
positive regulation of protein processing	1
plasminogen activation	1
mRNA transcription	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
exocytosis	1
regulation of exocytosis	1
positive regulation of secretion by cell	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
neurogenesis	1
regulation of nervous system development	1
regulation of cell development	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
positive regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of focal adhesion assembly	1
positive regulation of cell-substrate junction organization	1
positive regulation of cell junction assembly	1
protein localization to membrane	1
protein localization to cell periphery	1
positive regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
plasma membrane repair	1
positive regulation of cellular component organization	1
regulation of plasma membrane repair	1
metal ion binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

114 interactions, top by confidence:

A	B	Type	Score
TAB1	MAP3K7	psi-mi:“MI:0914”(association)	0.900
TAB1	HSPA8	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
S100A10	ANXA2	psi-mi:“MI:0403”(colocalization)	0.700
S100A10	ANXA2	psi-mi:“MI:0915”(physical association)	0.700
ANXA2	S100A10	psi-mi:“MI:0914”(association)	0.700
ERBB3	PIK3R2	psi-mi:“MI:0914”(association)	0.700
UQCRB	COX7A2L	psi-mi:“MI:0914”(association)	0.640
CCR10	S100A10	psi-mi:“MI:2364”(proximity)	0.630
CCR10	S100A10	psi-mi:“MI:0407”(direct interaction)	0.630
AHNAK	S100A10	psi-mi:“MI:0915”(physical association)	0.610
S100A10	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.610
NANOS2	S100A10	psi-mi:“MI:0915”(physical association)	0.560
USP2	S100A10	psi-mi:“MI:0915”(physical association)	0.560
S100A10	S100Z	psi-mi:“MI:0915”(physical association)	0.560
S100A10	MLKL	psi-mi:“MI:0915”(physical association)	0.560
S100A3	S100A10	psi-mi:“MI:0915”(physical association)	0.560
S100A10	ZGPAT	psi-mi:“MI:0915”(physical association)	0.560
ERBB3	S100A10	psi-mi:“MI:0915”(physical association)	0.550
TRPM4	S100A10	psi-mi:“MI:0407”(direct interaction)	0.540
S100A10	TRPM4	psi-mi:“MI:0915”(physical association)	0.540
ZNF428	S100A10	psi-mi:“MI:0914”(association)	0.530
MISP	OBSL1	psi-mi:“MI:0914”(association)	0.530
ANG	ANXA2	psi-mi:“MI:0914”(association)	0.480

BioGRID (181): S100A10 (Affinity Capture-Western), PLA2G4A (Affinity Capture-Western), ANXA2 (Affinity Capture-Western), S100A10 (Affinity Capture-MS), S100A10 (Affinity Capture-MS), S100A10 (Affinity Capture-MS), S100A10 (Affinity Capture-MS), S100A10 (Affinity Capture-MS), ANXA2 (Affinity Capture-MS), HLTF (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), AHNAK (Affinity Capture-MS), ANXA2 (Affinity Capture-Western), HLTF (Affinity Capture-Western), SUPT6H (Affinity Capture-Western)

ESM2 similar proteins: A0JN27, A5PJI5, G3MWR8, G3V9T7, O43681, O54984, O94925, P04163, P05943, P08207, P22234, P27003, P30626, P33764, P51583, P60902, P60903, P62504, P62818, P62819, Q13888, Q15303, Q2TBV5, Q2YDM2, Q3MHC2, Q5HZM6, Q5NVE6, Q5R4U9, Q5RB59, Q5RIC0, Q5TA45, Q5TDH0, Q5ZHS1, Q5ZIH0, Q61527, Q62956, Q64119, Q6NVL5, Q6P1K8, Q6PH85

Diamond homologs: A7K6Y8, A7K6Y9, O77691, O77791, P02632, P02633, P02634, P02638, P02639, P04163, P04271, P04631, P05109, P05942, P05943, P05964, P06702, P06703, P07091, P08207, P10462, P14069, P20930, P22793, P23297, P24479, P24480, P25815, P26447, P27003, P28318, P28782, P28783, P29034, P29377, P30801, P31725, P31949, P31950, P33763

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IFNG	“up-regulates quantity by expression”	S100A10	“transcriptional regulation”
STAT1	“up-regulates quantity by expression”	S100A10	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
PIP3 activates AKT signaling	7	8.2×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

262 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151986092:CACTT:C	donor_loss	1.0000
1:151986093:ACTTA:A	donor_loss	1.0000
1:151986095:TTA:T	donor_loss	1.0000
1:151986096:TAC:T	donor_loss	1.0000
1:151986097:A:AC	donor_gain	1.0000
1:151986097:AC:A	donor_loss	1.0000
1:151986097:ACTT:A	donor_gain	1.0000
1:151986097:ACTTC:A	donor_gain	1.0000
1:151986098:C:CA	donor_gain	1.0000
1:151986098:CT:C	donor_gain	1.0000
1:151986098:CTT:C	donor_gain	1.0000
1:151986098:CTTC:C	donor_gain	1.0000
1:151986098:CTTCC:C	donor_gain	1.0000
1:151986100:T:TA	donor_gain	1.0000
1:151986251:CCTA:C	acceptor_loss	1.0000
1:151986252:C:CA	acceptor_loss	1.0000
1:151986252:C:CC	acceptor_gain	1.0000
1:151983323:TT:T	acceptor_gain	0.9900
1:151984166:C:CT	acceptor_gain	0.9900
1:151986101:C:A	donor_gain	0.9900
1:151986247:GAAGC:G	acceptor_gain	0.9900
1:151986249:AGC:A	acceptor_gain	0.9900
1:151986250:GC:G	acceptor_gain	0.9900
1:151986251:CC:C	acceptor_gain	0.9900
1:151986253:T:A	acceptor_loss	0.9900
1:151986262:A:C	acceptor_gain	0.9900
1:151983321:GATT:G	acceptor_gain	0.9800
1:151983321:GATTC:G	acceptor_loss	0.9800
1:151983322:ATTC:A	acceptor_loss	0.9800
1:151983323:TTC:T	acceptor_loss	0.9800

AlphaMissense

664 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151986183:A:C	F16L	0.999
1:151986183:A:T	F16L	0.999
1:151986185:A:G	F16L	0.999
1:151986154:A:G	L26S	0.998
1:151983221:A:G	L79P	0.997
1:151983221:A:T	L79H	0.997
1:151983233:A:G	L75P	0.997
1:151983250:G:C	F69L	0.997
1:151983250:G:T	F69L	0.997
1:151983252:A:G	F69L	0.997
1:151986139:A:G	L31P	0.997
1:151983224:C:T	G78D	0.996
1:151983293:A:G	I55T	0.996
1:151983293:A:T	I55K	0.995
1:151983196:A:C	F87L	0.994
1:151983196:A:T	F87L	0.994
1:151983198:A:G	F87L	0.994
1:151983225:C:G	G78R	0.994
1:151983227:G:T	A77E	0.994
1:151986105:A:C	F42L	0.994
1:151986105:A:T	F42L	0.994
1:151986107:A:G	F42L	0.994
1:151986130:A:G	L34P	0.994
1:151986184:A:G	F16S	0.994
1:151986185:A:T	F16I	0.994
1:151983210:A:G	C83R	0.993
1:151983224:C:A	G78V	0.993
1:151983281:A:G	L59P	0.993
1:151986106:A:G	F42S	0.993
1:151986209:C:G	A8P	0.993

dbSNP variants (sampled 300 via entrez): RS1000063220 (1:151994483 G>A), RS1000761544 (1:151982779 G>A), RS1000807360 (1:151993903 G>C,T), RS1000855432 (1:151986525 G>A), RS1001182848 (1:151990414 A>G), RS1001372169 (1:151989077 A>C,G), RS1001501798 (1:151990926 T>C), RS1001532912 (1:151990671 G>C), RS1001942884 (1:151990820 C>A,G), RS1002412615 (1:151990519 G>A), RS1002529680 (1:151983969 G>A), RS1002617920 (1:151989148 G>A), RS1002691117 (1:151995745 A>G), RS1002942975 (1:151992411 G>A), RS1002962274 (1:151989438 A>C)

Disease associations

OMIM: gene MIM:114085 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST005649_5	Urinary metabolite ratios in chronic kidney disease	1.000000e-12
GCST005651_1	Urinary metabolite levels in chronic kidney disease	9.000000e-09
GCST006479_126	Diverticular disease	2.000000e-10
GCST008916_82	Asthma	5.000000e-27
GCST008916_88	Asthma	1.000000e-25
GCST012020_239	Serum metabolite levels	1.000000e-30
GCST012020_35	Serum metabolite levels	3.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0009959	diverticular disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1764939 (SINGLE PROTEIN), CHEMBL2111435 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

59 potent at pChembl≥5 of 123 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.42	Kd	382.3	nM	CHEMBL5653589
6.42	ED50	382.3	nM	CHEMBL5653589
5.92	IC50	1200	nM	CHEMBL3334803
5.92	IC50	1202	nM	CHEMBL3334803
5.75	IC50	1800	nM	CHEMBL1766592
5.68	IC50	2100	nM	CHEMBL1766591
5.57	IC50	2692	nM	CHEMBL1766727
5.54	IC50	2884	nM	CHEMBL1766718
5.52	IC50	3000	nM	CHEMBL1766718
5.52	IC50	3000	nM	CHEMBL1766727
5.41	IC50	3890	nM	CHEMBL1766609
5.40	IC50	4000	nM	CHEMBL3334808
5.40	IC50	4000	nM	CHEMBL3334844
5.40	IC50	4000	nM	CHEMBL1766609
5.35	IC50	4467	nM	CHEMBL3334844
5.35	IC50	4467	nM	CHEMBL3334808
5.31	IC50	4898	nM	CHEMBL1766736
5.30	IC50	5000	nM	CHEMBL1766736
5.22	IC50	6000	nM	CHEMBL1766606
5.22	IC50	6000	nM	CHEMBL1766719
5.22	IC50	6000	nM	CHEMBL1766730
5.20	IC50	6310	nM	CHEMBL1766606
5.20	IC50	6310	nM	CHEMBL1766730
5.19	IC50	6457	nM	CHEMBL1766719
5.16	IC50	7000	nM	CHEMBL3334812
5.16	IC50	7000	nM	CHEMBL3334839
5.16	IC50	7000	nM	CHEMBL3334846
5.16	IC50	7000	nM	CHEMBL1766713
5.16	IC50	7000	nM	CHEMBL1766723
5.16	IC50	7000	nM	CHEMBL1766724
5.16	IC50	6918	nM	CHEMBL1766713
5.16	IC50	6918	nM	CHEMBL1766723
5.15	IC50	7079	nM	CHEMBL1766724
5.14	IC50	7244	nM	CHEMBL3334846
5.14	IC50	7244	nM	CHEMBL3334812
5.13	IC50	7413	nM	CHEMBL3334839
5.12	IC50	7586	nM	CHEMBL1766608
5.12	IC50	7586	nM	CHEMBL1766714
5.12	IC50	7586	nM	CHEMBL1766717
5.10	IC50	8000	nM	CHEMBL3334842
5.10	IC50	8000	nM	CHEMBL3334845
5.10	IC50	8000	nM	CHEMBL1766607
5.10	IC50	8000	nM	CHEMBL1766608
5.10	IC50	8000	nM	CHEMBL1766714
5.10	IC50	8000	nM	CHEMBL1766717
5.08	IC50	8318	nM	CHEMBL3334842
5.08	IC50	8318	nM	CHEMBL1766607
5.07	IC50	8511	nM	CHEMBL3334845
5.06	IC50	8800	nM	CHEMBL1766587
5.05	IC50	8913	nM	CHEMBL3334810

PubChem BioAssay actives

58 with measured affinity, of 202 total; 31 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149331: Binding affinity to human S100A10 incubated for 45 mins by Kinobead based pull down assay	kd	0.3823	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylsulfanylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-6-aminohexanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]pentanedioic acid	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	1.2000	uM
4-[3-[3-(4-aminophenyl)sulfanylphenyl]sulfonylphenyl]sulfanylaniline	592541: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by FRET assay	ic50	1.8000	uM
5-benzyl-4-methyl-2-[(4-methylphenyl)sulfonylamino]thiophene-3-carboxamide	592541: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by FRET assay	ic50	2.1000	uM
(4E)-4-[(4-chlorophenyl)-hydroxymethylidene]-1-(2-hydroxypropyl)-5-(4-propan-2-ylphenyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	2.6915	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(3-methoxypropyl)-5-(4-propan-2-ylphenyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	2.8840	uM
(4E)-5-[3,5-bis(trifluoromethyl)phenyl]-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	3.8904	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(furan-2-ylmethyl)-1,2,4-triazol-3-yl]sulfanyl]-N-(4-propan-2-ylphenyl)acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	4.0000	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(4-methoxyphenyl)-1,2,4-triazol-3-yl]sulfanyl]-N-[4-(trifluoromethyl)phenyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	4.0000	uM
(4E)-4-[(2-ethoxyphenyl)-hydroxymethylidene]-5-[3-fluoro-4-(trifluoromethyl)phenyl]-1-(3-methoxypropyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	4.8978	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)-5-[4-(trifluoromethyl)phenyl]pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	6.0000	uM
(4E)-4-[(4-chlorophenyl)-hydroxymethylidene]-1-prop-2-enyl-5-[4-(trifluoromethyl)phenyl]pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	6.0000	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-5-(4-propan-2-ylphenyl)-1-prop-2-enylpyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	6.0000	uM
(4E)-5-(3,5-dichlorophenyl)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	6.9183	uM
(4E)-4-[hydroxy-(3-methoxyphenyl)methylidene]-1-(2-hydroxypropyl)-5-(4-propan-2-ylphenyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	6.9183	uM
N-(4-bromophenyl)-2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(furan-2-ylmethyl)-1,2,4-triazol-3-yl]sulfanyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	7.0000	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(3-methoxypropyl)-1,2,4-triazol-3-yl]sulfanyl]-N-(4-propan-2-ylphenyl)acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	7.0000	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(4-methoxyphenyl)-1,2,4-triazol-3-yl]sulfanyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	7.0000	uM
(4E)-4-[(2-ethoxyphenyl)-hydroxymethylidene]-1-(2-hydroxypropyl)-5-(4-propan-2-ylphenyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	7.0000	uM
(4E)-5-[2,4-bis(trifluoromethyl)phenyl]-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	7.5858	uM
(4E)-5-[4-chloro-3-(trifluoromethyl)phenyl]-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	7.5858	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-methoxyethyl)-5-(4-propan-2-ylphenyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	7.5858	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-prop-2-enyl-1,2,4-triazol-3-yl]sulfanyl]-N-[4-(trifluoromethyl)phenyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	8.0000	uM
2-[[4-(4-chlorophenyl)-5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-1,2,4-triazol-3-yl]sulfanyl]-N-[4-(trifluoromethyl)phenyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	8.0000	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)-5-[3-(trifluoromethyl)phenyl]pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	8.0000	uM
N-(2,5-dimethylphenyl)-2-[4-[(E)-3-phenylprop-2-enyl]piperazin-1-yl]acetamide	592541: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by FRET assay	ic50	8.8000	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(furan-2-ylmethyl)-1,2,4-triazol-3-yl]sulfanyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	8.9125	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)-5-[4-(trifluoromethoxy)phenyl]pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	9.0000	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(3-methoxypropyl)-1,2,4-triazol-3-yl]sulfanyl]-N-[4-(trifluoromethyl)phenyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	9.5499	uM
N-(3,4-dimethylphenyl)-2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(furan-2-ylmethyl)-1,2,4-triazol-3-yl]sulfanyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	9.5499	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-prop-2-enyl-1,2,4-triazol-3-yl]sulfanyl]-N-(4-propan-2-ylphenyl)acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	9.7724	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	6
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	4
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	4
Decitabine	affects expression, affects methylation, affects cotreatment, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Vorinostat	affects cotreatment, affects expression, increases expression	3
Benzo(a)pyrene	increases expression, increases methylation	3
Cadmium Chloride	increases expression	3
bisphenol A	increases expression, decreases expression	2
arsenite	increases reaction, affects expression, affects binding	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
belinostat	increases expression, affects cotreatment	2
Arsenic Trioxide	increases expression, decreases response to substance	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Doxorubicin	decreases expression, increases expression	2
Formaldehyde	decreases expression, affects binding, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652373	Binding	Binding affinity to human S100A10 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

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1YV	Abcam A-549 S100A10 KO	Cancer cell line	Male
CVCL_D2CX	Abcam HCT 116 S100A10 KO	Cancer cell line	Male
CVCL_TJ95	HAP1 S100A10 (-) 1	Cancer cell line	Male
CVCL_XS38	HAP1 S100A10 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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