S100A4

Summary

S100A4 (S100 calcium binding protein A4, HGNC:10494) is a protein-coding gene on chromosome 1q21.3, encoding Protein S100-A4 (P26447). Calcium-binding protein that plays a role in various cellular processes including motility, angiogenesis, cell differentiation, apoptosis, and autophagy.

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 motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 6275 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 16 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002961

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10494
Approved symbol	S100A4
Name	S100 calcium binding protein A4
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	P9KA, 18A2, PEL98, 42A, FSP1
Ensembl gene	ENSG00000196154
Ensembl biotype	protein_coding
OMIM	114210
Entrez	6275

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000354332, ENST00000368714, ENST00000368715, ENST00000368716, ENST00000468373, ENST00000481009, ENST00000854969, ENST00000854970, ENST00000854971, ENST00000854972, ENST00000854973, ENST00000854974, ENST00000942410, ENST00000942411, ENST00000942412, ENST00000942413

RefSeq mRNA: 2 — MANE Select: NM_002961 NM_002961, NM_019554

CCDS: CCDS1042

Canonical transcript exons

ENST00000368716 — 3 exons

Exon	Start	End
ENSE00001410588	153543621	153543923
ENSE00001423160	153545753	153545806
ENSE00003602068	153544654	153544809

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 172.1782 / max 3914.8893, expressed in 1616 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14646	169.0433	1524
14643	1.8608	806
14644	0.4188	257
14642	0.2056	106
14641	0.1762	75
14648	0.1729	90
14645	0.1266	43
14647	0.0882	35
14653	0.0858	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
synovial joint	UBERON:0002217	99.97	gold quality
monocyte	CL:0000576	99.92	gold quality
granulocyte	CL:0000094	99.91	gold quality
mononuclear cell	CL:0000842	99.91	gold quality
palpebral conjunctiva	UBERON:0001812	99.91	gold quality
leukocyte	CL:0000738	99.90	gold quality
descending thoracic aorta	UBERON:0002345	99.89	gold quality
saphenous vein	UBERON:0007318	99.84	gold quality
nasal cavity epithelium	UBERON:0005384	99.83	gold quality
ascending aorta	UBERON:0001496	99.82	gold quality
thoracic aorta	UBERON:0001515	99.82	gold quality
layer of synovial tissue	UBERON:0007616	99.82	gold quality
blood	UBERON:0000178	99.78	gold quality
periodontal ligament	UBERON:0008266	99.76	gold quality
tendon of biceps brachii	UBERON:0008188	99.75	gold quality
right coronary artery	UBERON:0001625	99.70	gold quality
nasal cavity mucosa	UBERON:0001826	99.67	gold quality
calcaneal tendon	UBERON:0003701	99.66	gold quality
decidua	UBERON:0002450	99.64	gold quality
tendon	UBERON:0000043	99.63	gold quality
upper lobe of left lung	UBERON:0008952	99.63	gold quality
upper lobe of lung	UBERON:0008948	99.61	gold quality
mammalian vulva	UBERON:0000997	99.60	gold quality
coronary artery	UBERON:0001621	99.59	gold quality
left coronary artery	UBERON:0001626	99.59	gold quality
blood vessel layer	UBERON:0004797	99.59	gold quality
urethra	UBERON:0000057	99.58	gold quality
right lung	UBERON:0002167	99.56	gold quality
aorta	UBERON:0000947	99.55	gold quality
skin of hip	UBERON:0001554	99.55	gold quality

Single-cell (SCXA)

Detected in 63 experiment(s), a significant marker in 47.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	9839.47
E-MTAB-10042	yes	8160.66
E-HCAD-4	yes	7723.23
E-CURD-122	yes	6984.25
E-CURD-112	yes	6962.36
E-MTAB-10432	yes	6795.19
E-MTAB-8495	yes	5661.07
E-MTAB-6701	yes	5130.39
E-MTAB-8530	yes	4782.29
E-MTAB-7407	yes	4487.92
E-CURD-88	yes	4460.53
E-GEOD-134144	yes	4311.44
E-HCAD-9	yes	3997.25
E-HCAD-10	yes	3897.41
E-MTAB-6108	yes	3573.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CIITA, CREBBP, CTNNB1, EP300, FOXC1, HIF1A, HNF4A, KAT7, LAMTOR5, MSX1, MYB, NFAT5, PTTG1, STAT4, TFAP2A

miRNA regulators (miRDB)

4 targeting S100A4, 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-3148	99.97	75.06	6478
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-371B-3P	94.48	66.59	345

Literature-anchored findings (GeneRIF, showing 40)

• crystallization and crystallographic analysis of structure (PMID:11752788)
• Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylation. (PMID:11786397)
• The level of S100A4 mRNA is higher in carcinomas compared to normal specimens. (PMID:11875708)
• the functional role of S100A4 in regulating endothelial cell growth and tumor metastasis involves interaction with the N-terminal half of Methionine Aminopeptidase 2. (PMID:11994292)
• Mutations of the cell cycle arrest gene p21WAF1, but not the metastasis-inducing gene S100A4, are frequent in oral squamous cell carcinomas from Sudanese toombak dippers and non-snuff-dippers from the Sudan, Scandinavia, USA and UK. (PMID:12168821)
• observed differential expression of S100A6 and S100A4 suggests that S100A6, rather than S100A4, is associated with human colorectal adenocarcinoma tumorigenesis and invasion/metastasis (PMID:12239456)
• Each subunit of S100A4 has two EF-hand Ca2+-binding domains: a pseudo-EF-hand (or S100-hand) formed by helices 1 and 2 that adopts a conformation similar to other members of the S100 family, and a typical EF-hand. (PMID:12379109)
• association seen between S100A4 expression and aggressive breast tumor phenotype (PMID:12439718)
• S100A4 stimulates the migration rate of astrocytic tumor cells by modifying the organization of their actin cytoskeleton. (PMID:12445462)
• S100A4 is a direct target of ERBB2 signaling in medulloblastoma cells (PMID:12517790)
• Expression of mts1 mRNA was affected by E-cadherin transfection. Loss of E-cadherin expression followed by mts1 expression may be important for increasing cell proliferation, motility & invasion activity in the progression of gall bladder cancer. (PMID:12532418)
• S100A4 showed the weakest expression of 3 S100 proteins (including S100A5 and S100A13) in the cells and fibers of the hippocampus and the temporal cortex at all stages examined (from 12 to 33 weeks of gestation). (PMID:12645008)
• S100A4 localizes to the leading edge in a calcium-independent manner (PMID:12756252)
• MTS1 regulates nonmuscle myosin IIA assembly by monomer sequestration and is able to regulate cell shape and motility through the modulation of myosin-IIA function. (PMID:14640694)
• one of the mechanisms by which S100A4 may exert its effect on metastasis of some tumors is by regulating the MMP-2 activity. (PMID:14713104)
• Mts1 acts as a neuroprotectant in primary cerebellar, dopaminergic, and hippocampal neurons induced to undergo cell death. (PMID:15334597)
• S100A4 is involved in tumor progression and metastasis. It may be a potential target for therapeutic intervention. (PMID:15579771)
• These findings suggest that (1) S100A4 plays a constitutive role in papillary carcinoma and (2) S100A4 may be a useful marker for early the detection of this carcinoma (PMID:15713996)
• S100A4 regulates the oligomerization of p53 tumor suppressor by binding to its tetramerization domain. (PMID:15781852)
• S100A4 protein alone or in a complex with annexin II accelerated tissue plasminogen activator-mediated plasminogen activation in solution and on the endothelial cell surface (PMID:15788416)
• S100A4 may exert its effect on invasion and metastasis of neuroblastoma cells by stimulating the motility of tumor cells as well as influencing the expression of MMP-2 (PMID:15852272)
• downregulation of mRNA and protein of the calcium binding protein S100A4 (metastasin) in MDA-MB-231/pIRES-EGFP-H2 transfectants (PMID:15956747)
• Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma. (PMID:16097057)
• S100A4 is a mediator of metastasis [review] (PMID:16243835)
• overexpression of S100A4 is associated with thyroid tumour invasion and metastasis and it may be a potential target for therapeutic intervention (PMID:16265347)
• Involvement of S100A2 and S100A4 in the progression of lung adenocarcinomas provides a list of targets regulated by S100A2 and S100A4. (PMID:16367903)
• Resaults suggest that in human breast cancer, S100A4 exerts some of its effects through angiogenesis. (PMID:16489073)
• These data suggest that S100A4, like SPARC, plays a supportive role in early in vitro cardiomyogenesis. (PMID:16554030)
• high S100A4 expression is related to a poor prognosis through hematogenous metastasis in pulmonary adenocarcinoma. (PMID:16685438)
• S100A4 overexpression combined with reduced E-cadherin expression is associated with tumor progression and metastasis in pancreatic cancer (PMID:16865243)
• Since both S100A4 and RAGE are up-regulated in osteoarthritis cartilage, this signaling pathway could contribute to cartilage degradation in this disease. (PMID:16948116)
• The nuclear expression of S100A4 is involved in the aggressive behavior of ovarian carcinoma and S100A4 is an autocrine/paracrine factor that plays an important role in the aggressiveness of ovarian carcinoma cells. (PMID:16984379)
• These data demonstrate that the S100A4 gene controls the invasive potential of human CaP cells through regulation of MMP-9 and that this association may contribute to metastasis of CaP cells. (PMID:16990429)
• results demonstrate frequent cytosolic overexpression of S100A2 and S100A4 in Barrett’s adenocarcinoma (PMID:17032501)
• All the data in the present study suggested that S100A4 might contribute to HCC invasion and metastasis through two paths of matrix metalloproteinase (MMP9) secretion regulation and strengthened motility and invasion properties. (PMID:17051636)
• Increased expression of S100A4 was observed in the medulla and papilla, but not the cortex of a human kidney in response to hypertonic stress (PMID:17200116)
• S100A4 protein is not expressed in benign or malignant prostatic epithelium nor in LNCaP and Du145 cells. (PMID:17219414)
• high-grade glioblastomas express higher amount of S100A4/Mts1 than low-grade astrocytic tumors (PMID:17223348)
• Expression of S100A4 protein was observed in 8 invasive carcinomas (80%), 5 high-grade dysphasia/carcinoma in situ cases (83%), and 0 low-grade dysplasia. (PMID:17276942)
• Overexpression of S100A4 in rheumatoid arthritis synovial tissue can influence p53 function and modulate the expression of several genes that are potentially implicated in the disease process. (PMID:17328050)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	s100s	ENSDARG00000036773
danio_rerio	s100a10a	ENSDARG00000037425
danio_rerio	s100t	ENSDARG00000055589
mus_musculus	S100a4	ENSMUSG00000001020
rattus_norvegicus	S100a4	ENSRNOG00000011821

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), S100A5 (ENSG00000196420), S100A2 (ENSG00000196754), S100A10 (ENSG00000197747), S100A6 (ENSG00000197956)

Protein

Protein identifiers

Protein S100-A4 — P26447 (reviewed: P26447)

Alternative names: Calvasculin, Metastasin, Placental calcium-binding protein, Protein Mts1, S100 calcium-binding protein A4

All UniProt accessions (1): P26447

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-binding protein that plays a role in various cellular processes including motility, angiogenesis, cell differentiation, apoptosis, and autophagy. Increases cell motility and invasiveness by interacting with non-muscle myosin heavy chain (NMMHC) IIA/MYH9. Mechanistically, promotes filament depolymerization and increases the amount of soluble myosin-IIA, resulting in the formation of stable protrusions facilitating chemotaxis. Also modulates the pro-apoptotic function of TP53 by binding to its C-terminal transactivation domain within the nucleus and reducing its protein levels. Within the extracellular space, stimulates cytokine production including granulocyte colony-stimulating factor and CCL24 from T-lymphocytes. In addition, stimulates T-lymphocyte chemotaxis by acting as a chemoattractant complex with PGLYRP1 that promotes lymphocyte migration via CCR5 and CXCR3 receptors.

Subunit / interactions. Homodimer. Interacts with PPFIBP1 in a calcium-dependent mode. Interacts with PGLYRP1; this complex acts as a chemoattractant that promotes lymphocyte movement. Interacts with MYH9; this interaction increases cell motility. Interacts with Annexin 2/ANXA2. Interacts with TP53; this interaction promotes TP53 degradation. Interacts with CCR5. Interacts with FCGR3A; this interaction inhibits PKC-dependent phosphorylation of FCGR3A.

Subcellular location. Secreted. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitously expressed.

Similarity. Belongs to the S-100 family.

RefSeq proteins (2): NP_002952, NP_062427 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001751	S100/CaBP7/8-like_CS	Conserved_site
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR013787	S100_Ca-bd_sub	Domain
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR034325	S-100_dom	Domain

Pfam: PF01023

UniProt features (26 total): binding site 7, helix 6, strand 5, modified residue 3, domain 2, initiator methionine 1, chain 1, turn 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
4CFQ	X-RAY DIFFRACTION	1.37
4CFR	X-RAY DIFFRACTION	1.4
3C1V	X-RAY DIFFRACTION	1.5
4ETO	X-RAY DIFFRACTION	1.54
2Q91	X-RAY DIFFRACTION	1.63
7PSQ	X-RAY DIFFRACTION	1.91
3ZWH	X-RAY DIFFRACTION	1.94
3CGA	X-RAY DIFFRACTION	2.03
5LPU	X-RAY DIFFRACTION	2.1
4HSZ	X-RAY DIFFRACTION	2.25
3KO0	X-RAY DIFFRACTION	2.3
7PSP	X-RAY DIFFRACTION	2.61
3M0W	X-RAY DIFFRACTION	2.8
6T58	X-RAY DIFFRACTION	3.1
1M31	SOLUTION NMR
2LNK	SOLUTION NMR
2MRD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26447-F1	86.09	0.64

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 (7): 74; 28; 33; 63; 65; 67; 69

Post-translational modifications (3): 2, 7, 35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 444 (showing top): MODULE_52, BASSO_B_LYMPHOCYTE_NETWORK, MODULE_45, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, MODULE_128, CHEOK_RESPONSE_TO_HD_MTX_UP, MEF2_02, MODULE_16, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOLDRATH_ANTIGEN_RESPONSE, TERAMOTO_OPN_TARGETS_CLUSTER_4, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, MODULE_118, GOBP_TAXIS, GNF2_MCL1

GO Biological Process (3): epithelial to mesenchymal transition (GO:0001837), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive chemotaxis (GO:0050918)

GO Molecular Function (10): RNA binding (GO:0003723), actin binding (GO:0003779), calcium ion binding (GO:0005509), chemoattractant activity (GO:0042056), identical protein binding (GO:0042802), transition metal ion binding (GO:0046914), calcium-dependent protein binding (GO:0048306), RAGE receptor binding (GO:0050786), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), extracellular matrix (GO:0031012), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
metal ion binding	2
protein binding	2
cytoplasm	2
mesenchymal cell differentiation	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
chemotaxis	1
nucleic acid binding	1
cytoskeletal protein binding	1
receptor ligand activity	1
positive chemotaxis	1
calcium ion binding	1
signaling receptor binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
external encapsulating structure	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3902 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S100A4	ANXA2	P07355	987
S100A4	TP53	P04637	981
S100A4	AGER	Q15109	981
S100A4	FGF2	P09038	868
S100A4	EGF	P01133	828
S100A4	MYH9	P35579	824
S100A4	SMAD3	P84022	722
S100A4	SDF4	Q9BRK5	722
S100A4	VIM	P08670	711
S100A4	HRNR	Q86YZ3	679
S100A4	GAPDH	P00354	678
S100A4	CDH1	P12830	665
S100A4	FN1	P02751	655
S100A4	KRT19	P08727	642
S100A4	ANXA1	P04083	629

IntAct

125 interactions, top by confidence:

A	B	Type	Score
TP53	TP53	psi-mi:“MI:0915”(physical association)	0.980
S100A4	MYH9	psi-mi:“MI:0407”(direct interaction)	0.950
MYH9	S100A4	psi-mi:“MI:0407”(direct interaction)	0.950
S100A4	MYH9	psi-mi:“MI:0915”(physical association)	0.950
MYH9	S100A4	psi-mi:“MI:0915”(physical association)	0.950
S100B	S100A4	psi-mi:“MI:0915”(physical association)	0.870
S100B	S100A4	psi-mi:“MI:0914”(association)	0.870
S100A4	S100B	psi-mi:“MI:0915”(physical association)	0.870
S100A4	TP53	psi-mi:“MI:0407”(direct interaction)	0.850
TP53	S100A4	psi-mi:“MI:0407”(direct interaction)	0.850
S100A4	TP53	psi-mi:“MI:0915”(physical association)	0.850
TP53	S100A4	psi-mi:“MI:0403”(colocalization)	0.850

BioGRID (164): S100B (Two-hybrid), S100A4 (Affinity Capture-RNA), S100A4 (Affinity Capture-RNA), S100A4 (Two-hybrid), S100A4 (Two-hybrid), S100A4 (Two-hybrid), S100A4 (Biochemical Activity), S100B (Two-hybrid), XIAP (Affinity Capture-MS), IGHG3 (Affinity Capture-MS), NPAT (Affinity Capture-MS), S100A4 (Affinity Capture-MS), S100A4 (Affinity Capture-MS), S100A4 (Affinity Capture-MS), S100A4 (Affinity Capture-MS)

ESM2 similar proteins: O77691, O77791, P02638, P02639, P04271, P04354, P04467, P04631, P05937, P05942, P05964, P06702, P06703, P07091, P07171, P10462, P12658, P14069, P23297, P24479, P25815, P26447, P27004, P28318, P29034, P30801, P31151, P35466, P35467, P50114, P56565, P79105, P79880, P80310, P80511, P97352, Q0VCM0, Q14ST5, Q28050, Q2EN75

Diamond homologs: A7K6Y9, O77691, O77791, P02632, P02633, P02634, P02638, P02639, P04271, P04631, P05942, P05964, P06702, P06703, P07091, P10462, P14069, P20930, P23297, P24480, P25815, P26447, P27003, P28318, P28783, P29034, P29377, P30801, P33763, P33764, P35466, P35467, P50114, P50116, P50117, P56565, P62818, P62819, P63083, P63084

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
CIITA	“down-regulates quantity by repression”	S100A4	“transcriptional regulation”
PTTG1	“up-regulates quantity by expression”	S100A4	“transcriptional regulation”
STAT4	“up-regulates quantity by expression”	S100A4	“transcriptional regulation”
LAMTOR5	“up-regulates quantity by expression”	S100A4	“transcriptional regulation”
SOD1	“up-regulates quantity”	S100A4
NFAT5	“up-regulates quantity by expression”	S100A4	“transcriptional regulation”
S100A4	“down-regulates activity”	MYH9	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
ERBB2 Regulates Cell Motility	7	89.2×	2e-10
PI3K events in ERBB2 signaling	7	84.0×	2e-10
GRB2 events in ERBB2 signaling	6	68.0×	1e-08
GRB2 events in EGFR signaling	5	68.0×	3e-07
SHC1 events in EGFR signaling	5	63.7×	4e-07
SHC1 events in ERBB2 signaling	7	59.5×	2e-09
Signaling by ERBB2 TMD/JMD mutants	7	59.5×	2e-09
GAB1 signalosome	5	56.6×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	7	23.8×	7e-06
positive regulation of cell growth	5	12.6×	5e-03
negative regulation of apoptotic process	11	5.2×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

785 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153543935:AGAGG:A	acceptor_gain	1.0000
1:153543936:GAGG:G	acceptor_gain	1.0000
1:153543940:C:CC	acceptor_gain	1.0000
1:153544648:A:AC	donor_gain	1.0000
1:153544649:C:CC	donor_gain	1.0000
1:153544651:CACC:C	donor_loss	1.0000
1:153544652:A:AC	donor_gain	1.0000
1:153544652:A:C	donor_loss	1.0000
1:153544652:AC:A	donor_gain	1.0000
1:153544652:ACC:A	donor_gain	1.0000
1:153544652:ACCC:A	donor_gain	1.0000
1:153544653:C:CC	donor_gain	1.0000
1:153544653:CC:C	donor_gain	1.0000
1:153544653:CCC:C	donor_gain	1.0000
1:153544653:CCCC:C	donor_gain	1.0000
1:153544674:C:CA	donor_gain	1.0000
1:153547843:CAGT:C	acceptor_gain	1.0000
1:153547845:GT:G	acceptor_gain	1.0000
1:153547846:TC:T	acceptor_loss	1.0000
1:153547847:C:CC	acceptor_gain	1.0000
1:153547849:G:C	acceptor_gain	1.0000
1:153547849:G:GC	acceptor_gain	1.0000
1:153547852:C:CT	acceptor_gain	1.0000
1:153547853:A:T	acceptor_gain	1.0000
1:153547863:T:TC	acceptor_gain	1.0000
1:153548339:GCTCA:G	donor_loss	1.0000
1:153548340:CTCA:C	donor_loss	1.0000
1:153548341:TCAC:T	donor_loss	1.0000
1:153548342:CAC:C	donor_loss	1.0000
1:153548343:A:AC	donor_gain	1.0000

AlphaMissense

683 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153544747:G:C	F16L	0.998
1:153544747:G:T	F16L	0.998
1:153544749:A:G	F16L	0.998
1:153544709:A:T	L29H	0.996
1:153543849:G:C	F72L	0.993
1:153543849:G:T	F72L	0.993
1:153543851:A:G	F72L	0.993
1:153543850:A:G	F72S	0.992
1:153543817:G:T	A83D	0.991
1:153544694:A:G	L34P	0.991
1:153544709:A:G	L29P	0.990
1:153543880:A:G	L62S	0.989
1:153544748:A:G	F16S	0.989
1:153544685:A:G	L37P	0.988
1:153543844:T:A	E74V	0.986
1:153543856:A:T	V70E	0.986
1:153543866:C:G	D67H	0.986
1:153543876:G:C	D63E	0.986
1:153543876:G:T	D63E	0.986
1:153543865:T:A	D67V	0.985
1:153543818:C:G	A83P	0.984
1:153543850:A:C	F72C	0.984
1:153543877:T:A	D63V	0.984
1:153543878:C:G	D63H	0.984
1:153543841:T:G	Y75S	0.983
1:153543842:A:G	Y75H	0.983
1:153543865:T:G	D67A	0.983
1:153543839:A:G	C76R	0.982
1:153543877:T:G	D63A	0.980
1:153544749:A:T	F16I	0.980

dbSNP variants (sampled 300 via entrez): RS1001018269 (1:153546332 G>C,T), RS1001565381 (1:153546837 C>A,G,T), RS1001827765 (1:153547068 C>A,T), RS1003571555 (1:153544167 C>T), RS1004098143 (1:153543323 A>G), RS1005743756 (1:153547149 T>C), RS1005770068 (1:153544656 C>G,T), RS1005882891 (1:153545772 C>T), RS1005943355 (1:153546195 A>C), RS1005961597 (1:153544307 T>C), RS1006020801 (1:153547380 C>G), RS1006947044 (1:153545105 A>G), RS1007248171 (1:153546647 G>A), RS1007325289 (1:153545321 C>G,T), RS1007689948 (1:153546309 A>G)

Disease associations

OMIM: gene MIM:114210 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007269_40	Pulse pressure	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362976 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 170,587 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1563	DAUNORUBICIN HYDROCHLORIDE	4	28,670
CHEMBL359744	DOXORUBICIN HYDROCHLORIDE	4	141,917

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

ChEMBL bioactivities

52 potent at pChembl≥5 of 91 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.63	AC50	235	nM	DAUNORUBICIN HYDROCHLORIDE
6.59	AC50	257	nM	CHEMBL1700268
6.54	AC50	290	nM	CHEMBL1316831
6.52	AC50	304	nM	CHEMBL1719004
6.49	AC50	323	nM	DOXORUBICIN HYDROCHLORIDE
6.40	AC50	395	nM	CHEMBL1708554
6.39	AC50	406	nM	CHEMBL1700644
6.38	AC50	412	nM	CHEMBL1515691
6.30	AC50	505	nM	CHEMBL1502002
6.30	EC50	500	nM	CHEMBL433282
6.25	AC50	562	nM	CHEMBL1722325
6.11	AC50	774	nM	CHEMBL1904837
6.09	AC50	819	nM	CHEMBL1352607
5.96	AC50	1090	nM	CHEMBL1870075
5.95	AC50	1120	nM	CHEMBL585502
5.91	IC50	1230	nM	CHEMBL403183
5.89	AC50	1280	nM	CHEMBL1432627
5.89	IC50	1280	nM	CHEMBL6102195
5.85	AC50	1410	nM	CHEMBL1469444
5.80	EC50	1600	nM	CHEMBL417727
5.80	IC50	1570	nM	CHEMBL6096607
5.76	AC50	1740	nM	CHEMBL1469858
5.76	AC50	1720	nM	CHEMBL1456904
5.75	EC50	1800	nM	CHEMBL4462648
5.72	AC50	1910	nM	CHEMBL1567682
5.71	AC50	1930	nM	CHEMBL1437867
5.69	AC50	2040	nM	CHEMBL1733692
5.66	EC50	2200	nM	CHEMBL4469518
5.66	EC50	2200	nM	CHEMBL187347
5.60	EC50	2500	nM	CHEMBL4442350
5.60	EC50	2500	nM	CHEMBL50149
5.48	AC50	3300	nM	CHEMBL1608727
5.42	EC50	3800	nM	9,10-PHENANTHRENEQUINONE
5.39	AC50	4100	nM	CHEMBL1325203
5.39	EC50	4100	nM	CHEMBL1966669
5.37	EC50	4300	nM	CHEMBL4458188
5.33	IC50	4620	nM	CHEMBL6102786
5.32	AC50	4830	nM	CHEMBL1905929
5.29	AC50	5070	nM	CHEMBL1570497
5.22	AC50	6020	nM	CHEMBL1372303
5.20	AC50	6380	nM	CHEMBL1436378
5.17	AC50	6690	nM	CHEMBL1580375
5.15	AC50	7120	nM	CHEMBL2135878
5.14	AC50	7210	nM	CHEMBL1448906
5.12	EC50	7600	nM	CHEMBL429095
5.09	EC50	8100	nM	CHEMBL4555337
5.08	EC50	8400	nM	CHEMBL4521796
5.08	EC50	8300	nM	CHEMBL4567434
5.07	EC50	8600	nM	CHEMBL4564194
5.07	EC50	8600	nM	CHEMBL2002259

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	8
Niclosamide	decreases reaction, increases expression, decreases expression	4
Tretinoin	decreases expression, increases expression	4
bisphenol A	affects expression, decreases expression	3
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
bisphenol S	increases expression, decreases expression	3
Decitabine	affects expression, affects methylation, increases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
methylmercuric chloride	decreases expression	2
cobaltous chloride	decreases expression	2
tamibarotene	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
bisphenol AF	decreases expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Aspirin	decreases expression, increases expression	2
Atrazine	decreases reaction, increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Cisplatin	affects expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
geldanamycin	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1

ChEMBL screening assays

5 unique, capped per target: 4 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2354209	Functional	PubChem BioAssay. S100A4: HTS Measured in Biochemical System Using Plate Reader - 7045-01_Inhibitor_Dose_CherryPick_Activity. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4418534	Binding	Binding affinity to S100A4 (unknown origin) assessed as inhibition of S100A4/myosin-2A interaction using fluorescein-tagged myosin-2A peptide (1908 to 1923 residues) by fluorescence polarization assay	Chemical agents for the prevention of inhibition or tumor metastasis

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1HC	Abcam A-549 S100A4 KO	Cancer cell line	Male
CVCL_B2EH	Abcam HeLa S100A4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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