S100A6

Summary

S100A6 (S100 calcium binding protein A6, HGNC:10496) is a protein-coding gene on chromosome 1q21.3, encoding Protein S100-A6 (P06703). May function as calcium sensor and modulator, contributing to cellular calcium signaling.

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 stimulation of Ca2+-dependent insulin release, stimulation of prolactin secretion, and exocytosis. Chromosomal rearrangements and altered expression of this gene have been implicated in melanoma.

Source: NCBI Gene 6277 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 20 total
• Druggable target: yes
• MANE Select transcript: NM_014624

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10496
Approved symbol	S100A6
Name	S100 calcium binding protein A6
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	2A9, PRA, CABP
Ensembl gene	ENSG00000197956
Ensembl biotype	protein_coding
OMIM	114110
Entrez	6277

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 19 protein_coding, 1 retained_intron

ENST00000368719, ENST00000368720, ENST00000462776, ENST00000462951, ENST00000496817, ENST00000896466, ENST00000896467, ENST00000896468, ENST00000896469, ENST00000896470, ENST00000896471, ENST00000896472, ENST00000896473, ENST00000896474, ENST00000896475, ENST00000925440, ENST00000925441, ENST00000925442, ENST00000925443, ENST00000954696

RefSeq mRNA: 1 — MANE Select: NM_014624 NM_014624

CCDS: CCDS1040

Canonical transcript exons

ENST00000368719 — 3 exons

Exon	Start	End
ENSE00001447838	153535202	153535360
ENSE00003374776	153534599	153534830
ENSE00003451566	153535949	153535991

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 584.6016 / max 11008.5811, expressed in 1736 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14636	482.1263	1712
14637	82.7183	1678
14638	10.4695	1535
14634	8.4823	1305
14633	0.3646	190
14635	0.2597	123
14632	0.1808	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.97	gold quality
ascending aorta	UBERON:0001496	99.94	gold quality
thoracic aorta	UBERON:0001515	99.94	gold quality
right coronary artery	UBERON:0001625	99.94	gold quality
left coronary artery	UBERON:0001626	99.94	gold quality
right lung	UBERON:0002167	99.94	gold quality
descending thoracic aorta	UBERON:0002345	99.94	gold quality
mucosa of transverse colon	UBERON:0004991	99.94	gold quality
upper lobe of left lung	UBERON:0008952	99.94	gold quality
aorta	UBERON:0000947	99.93	gold quality
tibial nerve	UBERON:0001323	99.93	gold quality
coronary artery	UBERON:0001621	99.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.93	gold quality
metanephros cortex	UBERON:0010533	99.93	gold quality
popliteal artery	UBERON:0002250	99.92	gold quality
tibial artery	UBERON:0007610	99.92	gold quality
upper lobe of lung	UBERON:0008948	99.92	gold quality
transverse colon	UBERON:0001157	99.91	gold quality
rectum	UBERON:0001052	99.90	gold quality
gall bladder	UBERON:0002110	99.90	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.90	gold quality
stromal cell of endometrium	CL:0002255	99.89	gold quality
endocervix	UBERON:0000458	99.89	gold quality
left lobe of thyroid gland	UBERON:0001120	99.88	gold quality
mucosa of stomach	UBERON:0001199	99.87	gold quality
monocyte	CL:0000576	99.86	gold quality
right lobe of thyroid gland	UBERON:0001119	99.86	gold quality
lower esophagus mucosa	UBERON:0035834	99.86	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.86	gold quality
leukocyte	CL:0000738	99.85	gold quality

Single-cell (SCXA)

Detected in 74 experiment(s), a significant marker in 49.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	21192.55
E-CURD-46	yes	16093.32
E-HCAD-1	yes	15180.95
E-MTAB-10287	yes	14531.05
E-HCAD-8	yes	12081.37
E-CURD-88	yes	11197.57
E-MTAB-8142	yes	10842.45
E-HCAD-10	yes	10742.13
E-MTAB-6701	yes	10732.72
E-GEOD-149689	yes	10183.62
E-GEOD-114530	yes	9657.48
E-CURD-112	yes	9168.52
E-HCAD-23	yes	9074.31
E-HCAD-24	yes	8727.45
E-MTAB-10432	yes	8558.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, HNF4A, LEF1, NFKB1, NFKB, NFKBIA, RELA, SP1, TP53, USF1

Literature-anchored findings (GeneRIF, showing 40)

• findings suggest that up-regulation of FRalpha gene and calcyclin gene expressions induced by Allitridi may play an important role in human gastric cancer cell differentiation (PMID:11925593)
• Results are consistent with S100A6, and most likely other S100 proteins, functioning as Ca(2+) sensors in a way analogous to the prototypical sensors calmodulin and troponin C. (PMID:11937060)
• 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)
• Sgt1 binds to S100A6 in a calcium-regulated manner (PMID:12746458)
• These results suggest that NF-kappaB transcription factor contributes to the activation of S100A6 gene expression in response to tumor necrosis factor alpha in HepG2 cells. (PMID:12859951)
• calcyclin has a role as an accessory protein involved in the cation-sensing pathway in osteoblasts (PMID:14584893)
• Agents evoking oxidative stress activate calcyclin gene via the antioxidant response element in its promoter (PMID:15878395)
• while S100A6 is commonly overexpressed in human osteosarcoma, loss of its expression correlates with a metastatic phenotype (PMID:16157226)
• S100A6 has a role in progression of pancreatic neoplasms (PMID:16278400)
• Depletion of the endogenous USF pool evokes a severe inhibition of S100A6 gene promoter activity. S100A6 gene promoter activity can be stimulated by palmitate and that mutation of the -283/-278 E-box sequence completely blocks this stimulation. (PMID:16288473)
• This suggests that the interaction of Sgt1 with Hsp70 and Hsp90 is regulated by S100A6 in a Ca(2+)-dependent manner. (PMID:17466273)
• Cell-specific S100A6 expression is under control of epigenetic mechanisms in skin epithelial and neoplastic cells. (PMID:17495951)
• S100A6 might be involved in the processing of apoptosis by modulating the transcriptional regulation of caspase-3. (PMID:17721932)
• S100A6 modulates cell survival by interacting with distinct RAGE immunglobulin domains. (PMID:17726019)
• S100A6 expression may distinguish squamous cell carcinomas from basal cell carcinomas (BCC), microcystic adnexal carcinomas from BCC and hidradenoma from other adnexal tumors (PMID:18201235)
• Findings suggest S100A6 may play an important role in osteosarcoma metastasis and may be considered a prognostic marker. (PMID:18612712)
• Survival results obtained in p53-negative stage I NSCLC cases support the proposed pro-apoptotic function of S100A6 and suggest the hypothesis of a cross regulation between these two proteins. (PMID:18620780)
• S100A2 and S100A6 interact with another TPR protein Tom70 and regulate the Tom70-ligand interaction in vitro (PMID:18669640)
• wild type p53 suppressed the S100A6 promoter up to 12-fold in a dose-dependent manner (PMID:18714402)
• S100A6 is induced by tumor necrosis factor-alpha via an NF-kappaB-dependent mechanism, serving a role in homeostasis to limit tumor necrosis factor-alpha-induced apoptosis by regulating p53 phosphorylation (PMID:18753141)
• We found that the presence of S100A6 results in higher p53 transcriptional activity which is also reflected by higher cell susceptibility to apoptosis evoked by hydrogen peroxide. (PMID:18765292)
• series of structure-based SIP mutations showed reduced S100A6 binding affinity, setting the stage for direct functional analysis of S100A6-SIP interactions (PMID:18803400)
• S100A6 differentially expressed in primary hepatocellular carcinoma , primary colorectal, and liver metastases (PMID:19048101)
• S100A6 expression level in cancer and metastatic lymph node was significantly higher than their matched non-neoplastic mucosa. S100A6 overexpression was associated with larger tumor size and deeper invasion. (PMID:19062716)
• S100A6 bound more tightly to tetrameric than to monomeric p53. (PMID:19297317)
• the combination of strong immunoreactivity for S100A6, in nested dermal spindle cell proliferations, and lack of S100 protein or keratin, supports a diagnosis of cellular neurothekeoma. (PMID:19542912)
• The present results suggest the utility of S100A6 immunohistochemistry as a marker for estimation of malignancy in adenocarcinoma with a bronchioloalveolar carcinoma component. (PMID:19712129)
• S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility. (PMID:19724273)
• Proteomic profiling in distinct cellular compartments led to the identification of a novel p53-dependent biomarker of telomere dysfunction, S100A6. (PMID:19834903)
• S100A6 concentration predicts peritoneal tumor burden in mice with epithelial ovarian cancer and is associated with advanced stage in patients (PMID:19888321)
• S100A6 is necessary for nuclear translocation of the Sgt1 protein (PMID:20213445)
• Results suggested that S100A6 plays an important role in the progression of gastric cancer, affecting patient prognosis, and is up-regulated by epigenetic regulation. (PMID:20581057)
• S100A1, S100A2, S100A4, S100A6 and S100B interacted with MDM2 (2-125). (PMID:20591429)
• S100A6 expression decreases along with cancerization in oral squamous cell carcinoma. (PMID:20596636)
• This study supports a role of S100A6 in thyroid tumorigenesis and as a potential aid in the discrimination between follicular thyroid tumors and papillary thyroid carcinoma. (PMID:20629554)
• In melanocytic neoplasms composed of small spindle cells, patchy S100A6 staining should not be interpreted as evidence of supporting a diagnosis of melanoma (PMID:21039744)
• Serum levels of S100B, S100A6 and S100P are associated with acute coronary syndrome, and serum levels and myocardial expression of these proteins are related to infarct size. (PMID:21663912)
• results show the presence of S100A6 in umbilical cord and suggest the involvement of this protein in intra- and extra-cellular signalling pathways in this tissue (PMID:21923636)
• the overexpression of thioredoxin,S100-A10 and S100-A6 specifically distinguished metastatic from non-metastatic tumors (PMID:21938494)
• Calcyclin was identified to be underexpressed in small cell lung cancers, as compared with non-small cell lung cancers and normal lung tissue. (PMID:22192801)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	s100s	ENSDARG00000036773
danio_rerio	s100t	ENSDARG00000055589
mus_musculus	S100a6	ENSMUSG00000001025
rattus_norvegicus	S100a6	ENSRNOG00000011647

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), S100A10 (ENSG00000197747)

Protein

Protein identifiers

Protein S100-A6 — P06703 (reviewed: P06703)

Alternative names: Calcyclin, Growth factor-inducible protein 2A9, MLN 4, Prolactin receptor-associated protein, S100 calcium-binding protein A6

All UniProt accessions (2): P06703, R4GN98

UniProt curated annotations — full annotation on UniProt →

Function. May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role in many physiological processes such as the reorganization of the actin cytoskeleton and in cell motility. Binds 2 calcium ions. Calcium binding is cooperative. (Microbial infection) Facilitates attachment and invasion of Toxoplasma gondii parasites.

Subunit / interactions. Homodimer; head to tail assembly of 2 subunits. Interacts with CACYBP in a calcium-dependent manner. Interacts with ANXA2 and ANXA11 (via N-terminus). Interacts with SUGT1. Interacts with TP53; has higher affinity for TP53 that is phosphorylated on its N-terminal domain, and lower affinity for TP53 that is phosphorylated on its C-terminal domain. Interacts with tropomyosin. Interacts with FKBP4. Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity. Interacts with TPPP; this interaction inhibits TPPP dimerization. (Microbial infection) Interacts with Toxoplasma gondii SAG1.

Subcellular location. Nucleus envelope. Cytoplasm. Cell membrane.

Post-translational modifications. The N-terminus is blocked.

Induction. Preferentially expressed when quiescent fibroblasts are stimulated to proliferate. It is inducible by growth factors and overexpressed in acute myeloid leukemias.

Miscellaneous. This protein co-purified with the prolactin receptor.

Similarity. Belongs to the S-100 family.

RefSeq proteins (1): NP_055439* (*=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
IPR034118	S-100A6	Family

Pfam: PF01023

UniProt features (28 total): binding site 7, helix 6, modified residue 4, sequence variant 4, strand 3, domain 2, chain 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1K8U	X-RAY DIFFRACTION	1.15
1K96	X-RAY DIFFRACTION	1.44
1K9K	X-RAY DIFFRACTION	1.76
1K9P	X-RAY DIFFRACTION	1.9
4YBH	X-RAY DIFFRACTION	2.4
2M1K	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06703-F1	87.47	0.40

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): 28; 33; 61; 63; 65; 67; 72

Post-translational modifications (4): 40, 46, 47, 47

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 433 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, MODULE_92, ZHAN_LATE_DIFFERENTIATION_GENES_UP, MODULE_64, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOZGIT_ESR1_TARGETS_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_NEUROGENESIS, GOCC_RUFFLE, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, BOYLAN_MULTIPLE_MYELOMA_D_DN, GOLDRATH_ANTIGEN_RESPONSE, BILD_HRAS_ONCOGENIC_SIGNATURE, TERAMOTO_OPN_TARGETS_CLUSTER_7

GO Biological Process (4): signal transduction (GO:0007165), axonogenesis (GO:0007409), positive regulation of fibroblast proliferation (GO:0048146), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (10): calcium ion binding (GO:0005509), tropomyosin binding (GO:0005523), zinc ion binding (GO:0008270), monoatomic ion transmembrane transporter activity (GO:0015075), protein homodimerization activity (GO:0042803), S100 protein binding (GO:0044548), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515), identical protein binding (GO:0042802), metal ion binding (GO:0046872)

GO Cellular Component (12): ruffle (GO:0001726), extracellular region (GO:0005576), nucleus (GO:0005634), nuclear envelope (GO:0005635), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), extracellular matrix (GO:0031012), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein binding	3
cytoplasm	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
positive regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
monoatomic ion transport	1
transmembrane transport	1
metal ion binding	1
cytoskeletal protein binding	1
transition metal ion binding	1
transmembrane transporter activity	1
monoatomic ion transmembrane transport	1
identical protein binding	1
protein dimerization activity	1
calcium ion binding	1
binding	1
cation binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular membrane-bounded organelle	1
nucleus	1
endomembrane system	1
organelle envelope	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
plasma membrane	1
cytoplasmic side of membrane	1
external encapsulating structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

2554 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S100A6	CACYBP	Q9HB71	991
S100A6	ANXA11	P50995	978
S100A6	S100A10	P08206	926
S100A6	RB1	P06400	921
S100A6	ANXA2	P07355	915
S100A6	TMSB10	P13472	843
S100A6	AGER	Q15109	840
S100A6	GAPDH	P00354	828
S100A6	SIAH1	Q8IUQ4	778
S100A6	TCHH	Q07283	748
S100A6	SPRR3	Q9UBC9	746
S100A6	ANXA1	P04083	739
S100A6	CALB1	P05937	720
S100A6	SDF4	Q9BRK5	720
S100A6	SPRR1A	P35321	719

IntAct

90 interactions, top by confidence:

A	B	Type	Score
TP53	TP53	psi-mi:“MI:0915”(physical association)	0.980
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
S100A6	TP53	psi-mi:“MI:0407”(direct interaction)	0.680
TP53	S100A6	psi-mi:“MI:0407”(direct interaction)	0.680
S100A6	CACYBP	psi-mi:“MI:0407”(direct interaction)	0.660
CACYBP	S100A6	psi-mi:“MI:0915”(physical association)	0.660
S100A6	S100B	psi-mi:“MI:2364”(proximity)	0.650
S100A6	S100B	psi-mi:“MI:0915”(physical association)	0.650
S100B	S100A6	psi-mi:“MI:0915”(physical association)	0.650
S100B	S100A6	psi-mi:“MI:0403”(colocalization)	0.650
KPNA2	S100A6	psi-mi:“MI:0407”(direct interaction)	0.610
KPNA2	S100A6	psi-mi:“MI:0915”(physical association)	0.610
S100A6	KPNA2	psi-mi:“MI:0407”(direct interaction)	0.610
UFM1	S100A6	psi-mi:“MI:0915”(physical association)	0.590
S100A6	PPID	psi-mi:“MI:0407”(direct interaction)	0.590
FKBP4	S100A6	psi-mi:“MI:0407”(direct interaction)	0.590
S100A6	PPID	psi-mi:“MI:0915”(physical association)	0.590
S100A6	FKBP4	psi-mi:“MI:0915”(physical association)	0.590
PPID	S100A6	psi-mi:“MI:0914”(association)	0.590
FKBP4	S100A6	psi-mi:“MI:0914”(association)	0.590
S100A6	PEX5	psi-mi:“MI:0915”(physical association)	0.560
PEX5	S100A6	psi-mi:“MI:0915”(physical association)	0.560
FAM25C	S100A6	psi-mi:“MI:0915”(physical association)	0.560
MDM2	S100A6	psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (273): S100A6 (Two-hybrid), TP53 (Reconstituted Complex), S100A6 (Co-fractionation), S100A6 (Affinity Capture-MS), S100A6 (Affinity Capture-MS), S100A6 (Affinity Capture-MS), S100A6 (Affinity Capture-MS), S100A6 (Affinity Capture-MS), S100A6 (Affinity Capture-MS), S100A6 (Affinity Capture-MS), S100A6 (Affinity Capture-MS), S100A6 (Affinity Capture-MS), S100A6 (Affinity Capture-RNA), S100A6 (Affinity Capture-MS), FOPNL (Reconstituted Complex)

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: A7K6Y8, A7K6Y9, O77691, O77791, P02632, P02633, P02634, P05964, P06703, P14069, P28318, P29377, P30801, P31151, P31725, P50116, P50117, P62818, P62819, P79105, P80511, P97816, Q14ST5, Q28050, Q2EN75, Q503K9, Q6S5I3, Q865V3, Q86SG5, Q8WXG8, P02638, P02639, P04271, P04631, P05942, P06702, P07091, P10462, P20930, P23297

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NfKb-p65/p50	“up-regulates quantity by expression”	S100A6	“transcriptional regulation”
NFKBIA	“down-regulates quantity by repression”	S100A6	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	S100A6	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 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
Signaling by ALK fusions and activated point mutants	5	17.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

402 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153534834:A:AC	acceptor_gain	1.0000
1:153535197:CTCA:C	donor_loss	1.0000
1:153535198:TCA:T	donor_loss	1.0000
1:153535199:CA:C	donor_loss	1.0000
1:153535200:A:AC	donor_gain	1.0000
1:153535200:A:T	donor_loss	1.0000
1:153535201:C:CT	donor_gain	1.0000
1:153535201:CCGA:C	donor_gain	1.0000
1:153535201:CCGAG:C	donor_gain	1.0000
1:153534828:CTT:C	acceptor_gain	0.9900
1:153534830:TC:T	acceptor_loss	0.9900
1:153534831:C:CC	acceptor_gain	0.9900
1:153534831:C:T	acceptor_loss	0.9900
1:153534834:A:C	acceptor_gain	0.9900
1:153534836:G:C	acceptor_gain	0.9900
1:153534836:G:GC	acceptor_gain	0.9900
1:153534839:T:C	acceptor_gain	0.9900
1:153534839:T:TC	acceptor_gain	0.9900
1:153535200:AC:A	donor_gain	0.9900
1:153535201:CC:C	donor_gain	0.9900
1:153535201:CCG:C	donor_gain	0.9900
1:153535361:C:CC	acceptor_gain	0.9900
1:153534826:AGCTT:A	acceptor_gain	0.9800
1:153534838:G:C	acceptor_gain	0.9800
1:153535356:TGGAG:T	acceptor_gain	0.9800
1:153535944:CTCA:C	donor_loss	0.9800
1:153535947:A:AC	donor_gain	0.9800
1:153535947:ACC:A	donor_loss	0.9800
1:153535948:C:CC	donor_gain	0.9800
1:153536107:CA:C	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000035379 (1:153534199 T>C), RS1001569357 (1:153535022 C>T), RS1002887494 (1:153535961 G>A), RS1003199194 (1:153537725 A>C), RS1003265446 (1:153536191 C>G), RS1005090577 (1:153536920 C>T), RS1005364699 (1:153537204 G>A), RS1009046907 (1:153535137 C>G,T), RS1009474837 (1:153536066 C>T), RS1009610633 (1:153535669 C>T), RS1010533240 (1:153535905 C>T), RS1010752142 (1:153537662 C>T), RS1011915358 (1:153537785 C>T), RS1013608676 (1:153536437 A>G), RS1013639790 (1:153536775 T>A,C)

Disease associations

OMIM: gene MIM:114110 | 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
GCST009367_1	HDL cholesterol levels x short total sleep time interaction (2df test)	7.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066977 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.93	Kd	118.1	nM	CHEMBL3752910
6.93	ED50	118.1	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149333: Binding affinity to human S100A6 incubated for 45 mins by Kinobead based pull down assay	kd	0.1181	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	7
Benzo(a)pyrene	decreases methylation, increases expression, increases ubiquitination	6
Aflatoxin B1	affects expression, increases expression	4
methylmercuric chloride	decreases expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Decitabine	affects methylation, increases expression	2
Panobinostat	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance	2
Diethylhexyl Phthalate	increases abundance, increases methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tetrachlorodibenzodioxin	increases expression, affects cotreatment, decreases expression	2
Nanotubes, Carbon	affects expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
shuanghuang shengbai	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
mancozeb	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
1-benzylimidazole	decreases expression	1
decamethrin	increases expression, increases ubiquitination	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
CHEMBL5652375	Binding	Binding affinity to human S100A6 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

Clinical trials (associated diseases)

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