S100A11

Summary

S100A11 (S100 calcium binding protein A11, HGNC:10488) is a protein-coding gene on chromosome 1q21.3, encoding Protein S100-A11 (P31949). Facilitates the differentiation and the cornification of keratinocytes.

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.

Source: NCBI Gene 6282 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 18 total
• Druggable target: yes
• MANE Select transcript: NM_005620

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10488
Approved symbol	S100A11
Name	S100 calcium binding protein A11
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	S100C
Ensembl gene	ENSG00000163191
Ensembl biotype	protein_coding
OMIM	603114
Entrez	6282

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000271638, ENST00000478109, ENST00000876489, ENST00000932478, ENST00000932479, ENST00000932480

RefSeq mRNA: 1 — MANE Select: NM_005620 NM_005620

CCDS: CCDS1009

Canonical transcript exons

ENST00000271638 — 3 exons

Exon	Start	End
ENSE00001045643	152036913	152037004
ENSE00003549624	152032506	152032823
ENSE00003640066	152033648	152033800

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1249.9107 / max 11920.8333, expressed in 1812 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14519	702.6561	1808
14518	542.0921	1803
14521	1.8554	371
14517	1.7624	929
14522	0.8773	289
14524	0.3112	134
14520	0.2496	106
14523	0.1067	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.94	gold quality
esophagus mucosa	UBERON:0002469	99.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.80	gold quality
metanephros cortex	UBERON:0010533	99.73	gold quality
monocyte	CL:0000576	99.72	gold quality
nasal cavity epithelium	UBERON:0005384	99.70	gold quality
oral cavity	UBERON:0000167	99.68	gold quality
minor salivary gland	UBERON:0001830	99.68	gold quality
granulocyte	CL:0000094	99.67	gold quality
right uterine tube	UBERON:0001302	99.67	gold quality
descending thoracic aorta	UBERON:0002345	99.67	gold quality
mouth mucosa	UBERON:0003729	99.67	gold quality
pharyngeal mucosa	UBERON:0000355	99.66	gold quality
endometrium epithelium	UBERON:0004811	99.66	gold quality
leukocyte	CL:0000738	99.65	gold quality
left coronary artery	UBERON:0001626	99.65	gold quality
mononuclear cell	CL:0000842	99.64	gold quality
skin of abdomen	UBERON:0001416	99.64	gold quality
ascending aorta	UBERON:0001496	99.64	gold quality
thoracic aorta	UBERON:0001515	99.64	gold quality
right lung	UBERON:0002167	99.64	gold quality
upper lobe of left lung	UBERON:0008952	99.64	gold quality
vagina	UBERON:0000996	99.63	gold quality
right coronary artery	UBERON:0001625	99.61	gold quality
tongue squamous epithelium	UBERON:0006919	99.60	gold quality
upper lobe of lung	UBERON:0008948	99.59	gold quality
gall bladder	UBERON:0002110	99.55	gold quality
bronchial epithelial cell	CL:0002328	99.54	gold quality
epithelium of bronchus	UBERON:0002031	99.54	gold quality
ectocervix	UBERON:0012249	99.54	gold quality

Single-cell (SCXA)

Detected in 72 experiment(s), a significant marker in 51.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	8713.83
E-MTAB-6653	yes	8103.44
E-GEOD-149689	yes	7639.06
E-MTAB-8142	yes	7435.59
E-ANND-2	yes	7007.27
E-MTAB-8207	yes	6773.33
E-MTAB-6505	yes	6654.32
E-CURD-122	yes	5391.45
E-MTAB-6108	yes	5042.07
E-CURD-126	yes	4628.69
E-GEOD-139324	yes	4361.34
E-CURD-112	yes	4341.78
E-MTAB-8410	yes	3163.25
E-MTAB-10485	yes	2986.42
E-HCAD-8	yes	2977.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, STAT3

miRNA regulators (miRDB)

17 targeting S100A11, 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-4533	100.00	69.48	2758
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-648	98.64	66.13	553
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-1293	96.16	64.69	916
HSA-MIR-2861	95.24	65.47	1056

Literature-anchored findings (GeneRIF, showing 40)

• S100C is a new tumor marker protein, the expression of which significantly decreases after malignant transformation of human tissues. (PMID:11873942)
• S100Cis a key mediator of the Ca(2+)-induced growth inhibition of human keratinocytes in culture, and may be mediate growth regulation in vivo as well. (PMID:14623863)
• that redistribution along microtubules is a mechanism whereby S100A11 is positioned at the cell periphery in preparation for transglutaminase-dependent crosslinking. (PMID:14962086)
• PKCalpha-S100C/A11-mediated pathway is involved in and essential for the growth inhibition of normal human keratinocytes cells by TGFbeta1. (PMID:15051732)
• Up-regulation of S100A11 was associated with the development of lymph node metastases in gastric cancer (PMID:15138568)
• Of several tested, only an N-terminal peptide with 19 amino acid residues induces apoptosis in human keratinocyte and squamous-cell carcinoma cell lines (PMID:15241500)
• findings suggest that S100A11 has an anti-apoptotic function and is related to the process of growth of human uterine leiomyoma (PMID:15322223)
• Down-regulation of S100C expression is associated with increasing tumor aggressiveness and poor prognosis in bladder cancer patients. (PMID:15701847)
• Down-regulation of S100C is associated with bladder cancer progression (PMID:15701847)
• Expression of S100A11, a putative tumor suppressor gene, is increased in the early stage of pancreatic carcinogenesis and decreased during subsequent progression to cancer. (PMID:17000675)
• S100C/A11-mediated pathway is at least partly involved in conferring upon human squamous cell cancers resistant to TGFbeta-induced growth suppression (PMID:17476473)
• The results indicated that the upregulation of S100A11 expression in non-small cell lung cancer tissues was significantly associated with higher tumor-node-metastasis stage (P = 0.001) and positive lymph node status (PMID:17537172)
• Proteomic mapping using a selective subcellular extraction kit revealed S100A11 as a new member of the S100 protein family modulated by glucocorticoids in keratinocytes. (PMID:17624315)
• Ca(2+)-dependent binding of S100A11 to ANXA1 facilitated the binding of the latter to cPLA(2), resulting in inhibition of cPLA(2) activity (PMID:17932043)
• These findings indicate that S100A11 plays a dual role in growth regulation of epithelial cells. (PMID:17978094)
• These findings suggest S100A11 could be helpful in the pathological study of colorectal cancer, especially for the classification of different stages in colorectal cancer. (PMID:18340452)
• S100/A11 and p21 gene expression was also found to be significantly lower in acute and chronic atopic dermatitis skin. (PMID:18385759)
• S100A11 targets Rad54B to sites of DNA DSB repair sites and has a role in p21-based regulation of cell cycle (PMID:18463164)
• Following transformation by transglutaminase 2, S100A11 acquires the capacity to signal through the p38 MAP kinase pathway, accelerate chondrocyte hypertrophy, and couple inflammation with chondrocyte activation to promote progression of osteoarthritis. (PMID:18523305)
• The expression level of S100C in lung cancer tissue was lower than that in ambient tissue. (PMID:18589612)
• Phosphorylation of S100A11 induces a structural perturbation in the N-terminal edge of helix 1 and enables the phosphoryl group to be exposed to the solvent, allowing it to be recognized by the binding partner, nucleolin. (PMID:18618420)
• These results identify two categories of S100 proteins: those exemplified by S100A4 that exclusively bind to the p53 TET domain; and those exemplified by S100B that additionally bind to the NRD. (PMID:18694925)
• S100A11 differentially expressed in primary hepatocellular carcinoma , primary colorectal, and liver (PMID:19048101)
• Inhibition of S100A11 gene expression impairs the ability of keratinocytes to control vaccinia virus replication via downregulation of IFN-lambda receptor IL-10R2. (PMID:19577285)
• A single phenyl-Sepharose column was sufficient for the purification of human S100A11 whereas HiTrap Q anion exchange followed by phenyl-Sepharose columns were required for the purification of S100A1. (PMID:20347987)
• Data support that S100A11 is a novel diagnostic marker in breast carcinoma. (PMID:20372844)
• S100A11 mediates HIMF-induced smooth muscle cell migration, vesicular exocytosis, and nuclear activation. (PMID:21139050)
• investigated S100A11 expression in various subtypes of lung cancer and explored its role in cell proliferation. (PMID:21861103)
• All three markers correlated significantly with regional lymph node metastasis: FXYD3 (p = 0.0110), S100A11 (p = 0.0071), and GSTM3 (p = 0.0173) in colon cancer lymphatic metastasis. (PMID:22430872)
• Endometrial S100A11 is a crucial intermediator in EGF-stimulated embryo adhesion, endometrium receptivity, and immunotolerance via affecting Ca2+ uptake and release from intracellular Ca2+ stores. (PMID:22869607)
• the structure of human calcium-bound S100A11. (PMID:22903637)
• Data suggest that S100A11 is involved in maintenance of p21-CIP1 (cyclin-dependent kinase inhibitor 1A) protein stability (up-regulation; down-regulation) and appears to function as inhibitor of apoptosis in keratinocytes. (PMID:23745637)
• Our data indicate that S100A11 overexpression exerts a protumoral functional role in papillary thyroid carcinoma pathogenesis. (PMID:23928665)
• The EGFRvIII-STAT3 pathway promotes cell migration and invasion by upregulating S100A11 in hepatocellular carcinoma. (PMID:24376686)
• Proteomic data suggest a limited protein set is involved in SET- (template activating factor-I-) mediated cytotoxicity of TCE (trichloroethylene) in hepatocytes; this set includes CFL1 (cofilin 1), PRDX2 (peroxiredoxin 2), and S100-A11 (calgizzarin). (PMID:24631019)
• metastatic cancer cells have elevated rate of cell injury and they rely on the S100A11-ANXA2 complex to enable cell membrane repair. S100A11 in a complex with Annexin A2 helps reseal the plasma membrane. (PMID:24806074)
• higher S100A11 expression was associated with statistically significant decrease in disease-free survival in clear cell renal cell carcinoma (PMID:26472670)
• the up-regulation of S100A11 plays a role in tumor progression, particularly in KRAS-mutated lung adenocarcinomas (PMID:26544866)
• S100A11 overexpression correlates with an aggressive malignant phenotype and may constitute a novel prognostic factor for HGSC (PMID:26574635)
• Furthermore, we identify flotillin-1 (FLOT1) and histone H1 as downstream factors for cytoplasmic and nuclear pathway of S100A11, which are required for LASP1-S100A11 axis-mediated epithelial-mesenchymal transition and colorectal cancer progression. (PMID:27181092)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	s100a11	ENSDARG00000093628
mus_musculus	S100a11	ENSMUSG00000027907
rattus_norvegicus	S100a11	ENSRNOG00000010105
rattus_norvegicus	AC117299.1	ENSRNOG00000037978
rattus_norvegicus	S100a11l1	ENSRNOG00000040101
rattus_norvegicus		ENSRNOG00000070857
rattus_norvegicus		ENSRNOG00000082608
rattus_norvegicus		ENSRNOG00000090721

Paralogs (21): CRNN (ENSG00000143536), S100A8 (ENSG00000143546), S100A7 (ENSG00000143556), S100B (ENSG00000160307), S100A1 (ENSG00000160678), 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), S100A6 (ENSG00000197956)

Protein

Protein identifiers

Protein S100-A11 — P31949 (reviewed: P31949)

Alternative names: Calgizzarin, Metastatic lymph node gene 70 protein, Protein S100-C, S100 calcium-binding protein A11

All UniProt accessions (2): P31949, V9HWH9

UniProt curated annotations — full annotation on UniProt →

Function. Facilitates the differentiation and the cornification of keratinocytes.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylation at Thr-10 by PRKCA significantly suppresses homodimerization and promotes association with NCL/nucleolin which induces nuclear translocation.

Miscellaneous. Binds two calcium ions per molecule with an affinity similar to that of the S-100 proteins.

Similarity. Belongs to the S-100 family.

RefSeq proteins (1): NP_005611* (*=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
IPR028482	S100A11	Family

Pfam: PF00036, PF01023

UniProt features (27 total): binding site 7, modified residue 7, helix 5, chain 2, strand 2, domain 2, initiator methionine 1, disulfide bond 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1V4Z	SOLUTION NMR
1V50	SOLUTION NMR
2LUC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31949-F1	89.14	0.72

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; 79; 33; 38; 68; 70; 72

Post-translational modifications (7): 1, 2, 3, 5, 6, 10, 27

Disulfide bonds (1): 13

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 402 (showing top): MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOCC_RUFFLE, MODULE_16, GOLDRATH_ANTIGEN_RESPONSE, GOBP_CELL_CELL_ADHESION

GO Biological Process (6): signal transduction (GO:0007165), negative regulation of DNA replication (GO:0008156), negative regulation of cell population proliferation (GO:0008285), positive regulation of smooth muscle cell migration (GO:0014911), regulation of cell population proliferation (GO:0042127), cell-cell adhesion (GO:0098609)

GO Molecular Function (7): calcium ion binding (GO:0005509), protein homodimerization activity (GO:0042803), S100 protein binding (GO:0044548), calcium-dependent protein binding (GO:0048306), cadherin binding involved in cell-cell adhesion (GO:0098641), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): ruffle (GO:0001726), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), adherens junction (GO:0005912), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	2
cell population proliferation	2
protein binding	2
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
DNA replication	1
regulation of DNA replication	1
negative regulation of DNA metabolic process	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
smooth muscle cell migration	1
regulation of smooth muscle cell migration	1
positive regulation of cell migration	1
cell adhesion	1
metal ion binding	1
identical protein binding	1
protein dimerization activity	1
calcium ion binding	1
cadherin binding	1
cell-cell adhesion	1
cell-cell adhesion mediator activity	1
binding	1
cation binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cell-cell junction	1
secretory granule	1
cytoplasmic vesicle lumen	1
extracellular vesicle	1

Protein interactions and networks

STRING

2592 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S100A11	ANXA1	P04083	993
S100A11	ANXA2	P07355	991
S100A11	AGER	Q15109	960
S100A11	NUCLEOLIN	P19338	748
S100A11	ANXA6	P08133	677
S100A11	A0A087WTN9	A0A087WTN9	659
S100A11	S100A16	Q96FQ6	615
S100A11	S100A7	P31151	597
S100A11	HRNR	Q86YZ3	592
S100A11	TCHHL1	Q5QJ38	572
S100A11	ANXA3	P12429	510
S100A11	SP3	Q02447	497
S100A11	CLIC1	O00299	493
S100A11	ANXA5	P08758	490
S100A11	CALML6	Q8TD86	487

IntAct

63 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
S100B	S100A6	psi-mi:“MI:0403”(colocalization)	0.650
TNF	S100A11	psi-mi:“MI:0407”(direct interaction)	0.620
S100A11	TNF	psi-mi:“MI:0407”(direct interaction)	0.620
S100A11	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
S100A11	TP53	psi-mi:“MI:0407”(direct interaction)	0.540
TRPM4	S100A11	psi-mi:“MI:0407”(direct interaction)	0.540
S100A11	TRPM4	psi-mi:“MI:0915”(physical association)	0.540
S100B	S100A11	psi-mi:“MI:0915”(physical association)	0.540
S100A11	S100B	psi-mi:“MI:0915”(physical association)	0.540
EGFR	XPOT	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
S100A11	MYH9	psi-mi:“MI:0407”(direct interaction)	0.440
S100A11	SLC8A1	psi-mi:“MI:0407”(direct interaction)	0.440
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
ERBB2	S100A11	psi-mi:“MI:0915”(physical association)	0.370
S100A11	S100A11	psi-mi:“MI:0915”(physical association)	0.370
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
RPA3	XRCC6	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
BUB1B	AP5Z1	psi-mi:“MI:0914”(association)	0.350
NEK8	TGM5	psi-mi:“MI:0914”(association)	0.350

BioGRID (96): S100A11 (Affinity Capture-RNA), S100A11 (Affinity Capture-RNA), S100A11 (Affinity Capture-RNA), S100A11 (Affinity Capture-MS), S100A11 (Reconstituted Complex), S100A11 (Affinity Capture-Western), ANXA1 (Affinity Capture-Western), PLA2G4A (Affinity Capture-Western), S100A11 (Proximity Label-MS), S100A11 (Affinity Capture-MS), S100A11 (Affinity Capture-MS), FOPNL (Reconstituted Complex), S100A11 (Affinity Capture-MS), S100A11 (Affinity Capture-MS), S100A11 (Affinity Capture-MS)

ESM2 similar proteins: A9JTH1, O73762, O77691, P02605, P02638, P02639, P04271, P04631, P05942, P05964, P06703, P07091, P10462, P14069, P22676, P23297, P24479, P25815, P26447, P27004, P29034, P30801, P31949, P31950, P35466, P35467, P42325, P47728, P50114, P50543, P56565, P79342, P79881, P97352, Q08331, Q0VCM0, Q2EN75, Q503K9, Q5RC36, Q6P8Y1

Diamond homologs: A7K6Y8, A7K6Y9, O77691, O77791, P02632, P02633, P02634, P02638, P02639, P04271, P04631, P05109, P05942, P05943, P05964, P06702, P06703, P07091, P14069, P20930, P22793, P23297, P24479, P24480, P25815, P27004, P27005, P28318, P28782, P28783, P29377, P30801, P31725, P31949, P31950, P33763, P35467, P50114, P50115, P50116

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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
Transcriptional regulation of granulopoiesis	5	12.3×	8e-03
Signaling by Interleukins	9	11.3×	4e-05
Interleukin-4 and Interleukin-13 signaling	5	10.1×	8e-03
Cytokine Signaling in Immune system	9	7.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	7	33.3×	2e-06
hematopoietic progenitor cell differentiation	5	19.5×	2e-03
cell morphogenesis	5	12.9×	5e-03
response to ethanol	5	12.0×	5e-03
regulation of gene expression	7	9.6×	2e-03
in utero embryonic development	7	8.3×	5e-03
positive regulation of gene expression	8	5.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

215 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152032824:C:CC	acceptor_gain	1.0000
1:152033642:CAGTA:C	donor_loss	1.0000
1:152033643:AGTAC:A	donor_loss	1.0000
1:152033644:GTAC:G	donor_loss	1.0000
1:152033645:TACC:T	donor_loss	1.0000
1:152033646:ACCT:A	donor_loss	1.0000
1:152033798:TGCCT:T	acceptor_loss	1.0000
1:152033799:GCC:G	acceptor_loss	1.0000
1:152033800:CCT:C	acceptor_loss	1.0000
1:152033800:CCTT:C	acceptor_gain	1.0000
1:152033801:C:CC	acceptor_gain	1.0000
1:152033801:C:CG	acceptor_loss	1.0000
1:152033802:T:C	acceptor_gain	1.0000
1:152033802:T:G	acceptor_loss	1.0000
1:152033803:T:C	acceptor_gain	1.0000
1:152033803:T:TC	acceptor_gain	1.0000
1:152034478:AG:A	donor_gain	1.0000
1:152034497:T:TA	donor_gain	1.0000
1:152036909:TTA:T	donor_loss	1.0000
1:152036910:TAC:T	donor_loss	1.0000
1:152036911:A:AC	donor_gain	1.0000
1:152036911:ACCAT:A	donor_loss	1.0000
1:152036912:C:CC	donor_gain	1.0000
1:152032819:TGGTT:T	acceptor_gain	0.9900
1:152032821:GTT:G	acceptor_gain	0.9900
1:152032822:TT:T	acceptor_gain	0.9900
1:152032823:TCTG:T	acceptor_loss	0.9900
1:152032824:CTG:C	acceptor_loss	0.9900
1:152032825:T:A	acceptor_loss	0.9900
1:152032827:C:CT	acceptor_gain	0.9900

AlphaMissense

696 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152033741:G:C	F21L	0.998
1:152033741:G:T	F21L	0.998
1:152033743:A:G	F21L	0.998
1:152032740:A:C	F80L	0.997
1:152032740:A:T	F80L	0.997
1:152032742:A:G	F80L	0.997
1:152032732:A:G	L83P	0.995
1:152032718:C:G	A88P	0.993
1:152032749:G:C	F77L	0.993
1:152032749:G:T	F77L	0.993
1:152032751:A:G	F77L	0.993
1:152033703:A:T	L34H	0.993
1:152032717:G:T	A88D	0.992
1:152033765:G:C	C13W	0.992
1:152032726:C:T	G85D	0.991
1:152033654:G:C	F50L	0.991
1:152033654:G:T	F50L	0.991
1:152033656:A:G	F50L	0.991
1:152033679:A:G	F42S	0.991
1:152033758:A:G	S16P	0.990
1:152033769:C:G	R12P	0.990
1:152032738:A:G	L81P	0.989
1:152033688:A:G	F39S	0.989
1:152032756:A:G	L75P	0.988
1:152033687:G:C	F39L	0.988
1:152033687:G:T	F39L	0.988
1:152033689:A:G	F39L	0.988
1:152032777:T:A	D68V	0.987
1:152033703:A:G	L34P	0.987
1:152033767:A:G	C13R	0.987

dbSNP variants (sampled 300 via entrez): RS1000079027 (1:152032301 A>C,G), RS1000514775 (1:152036995 G>A,T), RS1000733583 (1:152037210 T>A,C), RS1001401570 (1:152035811 A>T), RS1001665367 (1:152036415 C>T), RS1001954569 (1:152037538 C>T), RS1002810084 (1:152037293 C>T), RS1003071393 (1:152034432 A>G), RS1003320062 (1:152032073 TTCTAGTTCTTCATA>T), RS1003400680 (1:152038731 G>A), RS1004819712 (1:152033051 T>G), RS1005194169 (1:152034639 T>A), RS1005738973 (1:152037484 C>T), RS1006041476 (1:152038863 TG>T), RS1006122103 (1:152037110 G>A)

Disease associations

OMIM: gene MIM:603114 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST006661_183	Male-pattern baldness	1.000000e-10
GCST007563_31	Allergic disease (asthma, hay fever or eczema)	2.000000e-08
GCST007563_33	Allergic disease (asthma, hay fever or eczema)	3.000000e-11
GCST007564_24	Asthma or allergic disease (pleiotropy)	5.000000e-12
GCST007798_6	Asthma	2.000000e-20
GCST008916_82	Asthma	5.000000e-27
GCST008916_88	Asthma	1.000000e-25
GCST010984_1	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	2.000000e-15
GCST010985_38	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	2.000000e-47

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066254 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — EF-hand domain containing proteins

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
5.51	Kd	3060	nM	CHEMBL3752910
5.51	ED50	3060	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	2149332: Binding affinity to human S100A11 incubated for 45 mins by Kinobead based pull down assay	kd	3.0602	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	9
Cadmium Chloride	decreases methylation, increases abundance, increases expression, decreases expression	7
Benzo(a)pyrene	increases expression, increases methylation	6
methylmercuric chloride	decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects cotreatment, increases expression, increases abundance	3
Tetrachlorodibenzodioxin	increases expression	3
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	3
Tretinoin	affects cotreatment, increases expression	3
Cyclosporine	increases expression	3
Aflatoxin B1	affects expression, increases expression, increases methylation	3
mercuric bromide	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
Decitabine	affects expression, affects methylation	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Arsenic	affects methylation, increases abundance, increases expression	2
Cisplatin	increases expression, decreases reaction, increases cleavage, increases response to substance, affects expression (+1 more)	2
Doxorubicin	affects expression, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Nanotubes, Carbon	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	decreases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652374	Binding	Binding affinity to human S100A11 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

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2EF	Abcam HeLa S100A11 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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