S100A1

Summary

S100A1 (S100 calcium binding protein A1, HGNC:10486) is a protein-coding gene on chromosome 1q21.3, encoding Protein S100-A1 (P23297). Small calcium binding protein that plays important roles in several biological processes such as Ca(2+) homeostasis, chondrocyte biology and cardiomyocyte regulation.

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+-induced Ca2+ release, inhibition of microtubule assembly, and inhibition of protein kinase C-mediated phosphorylation. Reduced expression of this protein has been implicated in cardiomyopathies.

Source: NCBI Gene 6271 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_006271

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10486
Approved symbol	S100A1
Name	S100 calcium binding protein A1
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	S100-alpha
Ensembl gene	ENSG00000160678
Ensembl biotype	protein_coding
OMIM	176940
Entrez	6271

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000292169, ENST00000368696, ENST00000368698, ENST00000436839, ENST00000469893, ENST00000883563, ENST00000883564

RefSeq mRNA: 1 — MANE Select: NM_006271 NM_006271

CCDS: CCDS1047

Canonical transcript exons

ENST00000292169 — 3 exons

Exon	Start	End
ENSE00001053734	153628434	153628496
ENSE00003623117	153631698	153632039
ENSE00003648217	153630509	153630662

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 99.90.

FANTOM5 (CAGE): breadth broad, TPM avg 50.7505 / max 2876.5301, expressed in 812 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5412	50.4692	797
5414	0.1844	85
5413	0.0968	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.90	gold quality
right atrium auricular region	UBERON:0006631	99.82	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.74	gold quality
cardiac atrium	UBERON:0002081	99.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.62	gold quality
gastrocnemius	UBERON:0001388	99.50	gold quality
heart left ventricle	UBERON:0002084	99.35	gold quality
cardiac ventricle	UBERON:0002082	99.29	gold quality
right frontal lobe	UBERON:0002810	99.07	gold quality
left ventricle myocardium	UBERON:0006566	99.07	gold quality
spinal cord	UBERON:0002240	99.06	gold quality
diaphragm	UBERON:0001103	98.88	gold quality
amygdala	UBERON:0001876	98.87	gold quality
nucleus accumbens	UBERON:0001882	98.85	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.76	gold quality
gluteal muscle	UBERON:0002000	98.72	gold quality
hypothalamus	UBERON:0001898	98.68	gold quality
putamen	UBERON:0001874	98.48	gold quality
cingulate cortex	UBERON:0003027	98.31	gold quality
anterior cingulate cortex	UBERON:0009835	98.29	gold quality
triceps brachii	UBERON:0001509	98.23	gold quality
prefrontal cortex	UBERON:0000451	98.22	gold quality
muscle of leg	UBERON:0001383	98.11	gold quality
caudate nucleus	UBERON:0001873	98.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.70	gold quality
myocardium	UBERON:0002349	97.63	gold quality
muscle organ	UBERON:0001630	97.59	gold quality
left lobe of thyroid gland	UBERON:0001120	97.52	gold quality
right lobe of thyroid gland	UBERON:0001119	97.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.33	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	2504.65
E-MTAB-9435	yes	1800.77
E-MTAB-10855	yes	1527.97
E-MTAB-10287	yes	31.49
E-ANND-3	yes	4.97
E-HCAD-25	yes	4.33
E-MTAB-10885	no	1154.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting S100A1, 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-6798-5P	100.00	65.77	699
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Literature-anchored findings (GeneRIF, showing 40)

• The presence of the S100A1 in myocardial sarcoplasmic reticulum and myofibrils may be related to the known target proteins for S100A1 at these sites. (PMID:11829317)
• Impaired cardiac contractility response to hemodynamic stress in S100A1-deficient mice. (PMID:11909974)
• identification of the S100A1 C terminus (amino acids 75-94) and hinge region (amino acids 42-54) to differentially enhance sarcoplasmic reticulum Ca2+ release with a nearly 3-fold higher activity of the C terminus (PMID:12721284)
• S100A1 has a reglatory role in the contraction-relaxation cycle in the human heart (PMID:12804600)
• S100A1 protein serves as a cardioprotective factor in vitro (PMID:12960148)
• identified S100A1, but not calmodulin or other S100 proteins, as a potent molecular chaperone and a new member of the Hsp70/Hsp90 multichaperone complex (PMID:14638689)
• Synapsins and S100A1 interact in nerve terminals where coexpresssed; S100A1 cannot bind SV-associated synapsin I and may function as a cytoplasmic store of monomeric synapsin I; synapsin dimerization and interaction with S100A1 are mutually exclusive (PMID:15147519)
• Results demonstrate that restoration of S100A1 protein levels in failing myocardium by gene transfer may be a novel therapeutic strategy for the treatment of heart failure. (PMID:15578088)
• This study provides the first evidence that intracellular S100A1, depending on its subcellular location, modulates cardiac Ca2+-turnover via different Ca2+-regulatory proteins. (PMID:15654019)
• S100A1 was expressed in 2/15 clear cell RCCs, 11/15 papillary RCCs, 7/8 oncocytomas and in 0/7 chromophobe RCCs. (PMID:15780567)
• the three-dimensional structure of calcium-bound S100A1 was determined by multidimensional NMR spectroscopy and compared to the previously determined structure of apo-S100A1 (PMID:16169012)
• S-100 protein expression in tumour cells was associated with significantly decreased survival (PMID:16760135)
• analysis of the different reactivity pattern of S100A1 in the external auditory canal cholesteatoma (PMID:16969478)
• There may be a reverse relationship between the expression of VEGF and S100(+) DC in esophageal tumor tissue, VEGF could decrease the number of S100(+) DC and impair the immunological function of the body. (PMID:17210106)
• Report concludes that S100A1 and S100B are transcriptional targets of the SOX trio and mediate its inhibition of terminal differentiation of chondrocytes. (PMID:17396138)
• S100A1 immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. (PMID:17483815)
• Both S100A1B and S100BB were related to outcome after severe traumatic brain injury. Even though this study is small, it seems unlikely that separate analyses of the dimers are of any advantage compared with measuring S100B alone. (PMID:18193148)
• S100A4 immunohistochemistry may be valuable for predicting metastatic potential in papillary microcarcinomas (PMID:18360353)
• Elevated serum S-100 is associated with malignant melanoma. (PMID:18845991)
• Circulating S100A1B and S100BB are potential biomarkers in patients with malignant melanoma. S100BB should be considered as the preferred biomarker, showing potential in predicting both relapse and survival, in contrast to both S100 and S100A1B. (PMID:19011512)
• The cytologic differential diagnosis of spindle cell neoplasm with expression of S-100 protein should be broadened to include sarcomatoid renal cell carcinoma (PMID:19037854)
• S100A2 bound monomeric p53 as well as tetrameric, whereas S100A1 only bound monomeric p53. (PMID:19297317)
• the combination of CK7, S100A1 and claudin 8 immunohistochemistry can be useful for classifying tumours of overlapping histology as chromophobe renal cell carcinoma or renal oncocytomas. (PMID:19302533)
• S100A1 is a specific and sensitive immunohistochemical marker to differentiate nephrogenic adenoma from prostatic adenocarcinoma (PMID:19384190)
• S100A1B and S100BB are increased in urine collected from asphyxiated newborns who will develop hypoxic-ischemic encephalopathy (HIE) since first urination, and their measurement may be useful to early predict HIE. (PMID:19482672)
• S100A1 has been proven to play a critical role both in cardiac performance, blood pressure regulation and skeletal muscle function. (PMID:19538970)
• Data have identified S100A1 as valuable markers for chromophobe renal cell carcinomas. (PMID:19680475)
• These data suggest that S100A1 is a marker for poor prognosis of endometrioid subtypes of cancer. (PMID:19926575)
• The expression of S100A1 was low in benign melanocytic tumours and increased in malignant melanomas (PMID:20042890)
• 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)
• COX-2 and S-100 positive dendritic cells are highly expressed in laryngeal carcinoma tissue. (PMID:20429377)
• S100A1, S100A2, S100A4, S100A6 and S100B interacted with MDM2 (2-125). (PMID:20591429)
• Thermodynamics of zinc binding to human S100A2 (PMID:21090249)
• The three-dimensional structure of human apo(calcium free)S100A1 protein was determined by NMR spectroscopy (PMID:21296671)
• S100A1 and permanently active S100P inhibited the apoptosis signal-regulating kinase 1 (ASK1) and PP5 interaction, resulting the inhibition of dephosphorylation of phospho-ASK1 by PP5 (PMID:22399290)
• Calmodulin and S100A1 protein interact with N terminus of TRPM3 channel. (PMID:22451665)
• Uremia clearance using NHD is accompanied by improvement in LV strain, rotation, reduction in mass and volume index. Dialysis downregulates genes for cardiomyocyte apoptosis and fibrosis and upregulates S100A1, which may improve LV contractility. (PMID:22647434)
• S-Nitrosylation of S100A1 increases Ca(2+) binding and tunes the overall protein conformation. (PMID:22989881)
• Report downregulation of S100A1 expression in critical limb ischemia impairs postischemic angiogenesis via compromised proangiogenic endothelial cell function and nitric oxide synthase regulation. (PMID:23048072)
• the increased calcium binding affinity of S100A1 upon thionylation arises, most probably, from rearrangement of the hydrophobic core in its apo form (PMID:23351007)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	s100a1	ENSDARG00000015543
mus_musculus	S100a1	ENSMUSG00000044080
rattus_norvegicus	S100a1	ENSRNOG00000012410

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

Protein

Protein identifiers

Protein S100-A1 — P23297 (reviewed: P23297)

Alternative names: S-100 protein alpha chain, S-100 protein subunit alpha, S100 calcium-binding protein A1

All UniProt accessions (5): P23297, A0A0S2Z4H2, Q5T7Y4, Q5T7Y5, Q5T7Y6

UniProt curated annotations — full annotation on UniProt →

Function. Small calcium binding protein that plays important roles in several biological processes such as Ca(2+) homeostasis, chondrocyte biology and cardiomyocyte regulation. In response to an increase in intracellular Ca(2+) levels, binds calcium which triggers conformational changes. These changes allow interactions with specific target proteins and modulate their activity. Regulates a network in cardiomyocytes controlling sarcoplasmic reticulum Ca(2+) cycling and mitochondrial function through interaction with the ryanodine receptors RYR1 and RYR2, sarcoplasmic reticulum Ca(2+)-ATPase/ATP2A2 and mitochondrial F1-ATPase. Facilitates diastolic Ca(2+) dissociation and myofilament mechanics in order to improve relaxation during diastole.

Subunit / interactions. Dimer of either two alpha chains, or two beta chains, or one alpha and one beta chain. Also forms heterodimers with S100P. Interacts with AGER. Interacts with CAPZA1. Interacts with FKBP4. Interacts with RYR1 and RYR2. Interacts with CACYBP in a calcium-dependent manner. Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity. Interacts with ATP2A2 and PLN in a Ca(2+)-dependent manner. Interacts with mitochondrial F1-ATPase subunits ATP5F1A and ATP5F1B; these interactions increase F1-ATPase activity.

Subcellular location. Cytoplasm. Sarcoplasmic reticulum. Mitochondrion.

Tissue specificity. Highly prevalent in heart. Also found in lesser quantities in skeletal muscle and brain.

Post-translational modifications. Glutathionylated; glutathionylation increases affinity to calcium about 10-fold.

Miscellaneous. Able to bind zinc in vitro; the binding sites are different from the calcium binding sites. The physiological relevance of zinc binding is unclear. Physiological concentrations of potassium antagonize the binding of both divalent cations, especially affecting the high-affinity calcium-binding sites.

Similarity. Belongs to the S-100 family.

RefSeq proteins (1): NP_006262* (*=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
IPR028486	S100-A1	Family

Pfam: PF00036, PF01023

UniProt features (20 total): binding site 7, helix 6, strand 3, domain 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
5K89	X-RAY DIFFRACTION	2.25
2L0P	SOLUTION NMR
2LHL	SOLUTION NMR
2LLS	SOLUTION NMR
2LLT	SOLUTION NMR
2LLU	SOLUTION NMR
2LP2	SOLUTION NMR
2LP3	SOLUTION NMR
2LUX	SOLUTION NMR
2M3W	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23297-F1	82.15	0.36

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; 63; 65; 67; 69; 74

Post-translational modifications (1): 86

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-5602498	MyD88 deficiency (TLR2/4)
R-HSA-5603041	IRAK4 deficiency (TLR2/4)
R-HSA-5686938	Regulation of TLR by endogenous ligand
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-1643685	Disease
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-5260271	Diseases of Immune System
R-HSA-5602358	Diseases associated with the TLR signaling cascade
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 231 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_CIRCULATORY_SYSTEM_PROCESS, SWEET_KRAS_ONCOGENIC_SIGNATURE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GGGTGGRR_PAX4_03, BOYLAN_MULTIPLE_MYELOMA_D_DN, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, ONKEN_UVEAL_MELANOMA_UP, GOBP_SPROUTING_ANGIOGENESIS, GOBP_NEURAL_NUCLEUS_DEVELOPMENT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_SUBSTANTIA_NIGRA_DEVELOPMENT

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of heart contraction (GO:0008016), substantia nigra development (GO:0021762), intracellular signal transduction (GO:0035556), vasodilation (GO:0042311), positive regulation of sprouting angiogenesis (GO:1903672)

GO Molecular Function (8): calcium ion binding (GO:0005509), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), S100 protein binding (GO:0044548), calcium-dependent protein binding (GO:0048306), ATPase binding (GO:0051117), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (13): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), Golgi apparatus (GO:0005794), cytosol (GO:0005829), sarcoplasmic reticulum (GO:0016529), Z disc (GO:0030018), M band (GO:0031430), protein-containing complex (GO:0032991), A band (GO:0031672), I band (GO:0031674)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Toll-like Receptor Cascades	3
Diseases associated with the TLR signaling cascade	2
Immune System	2
Toll Like Receptor 2 (TLR2) Cascade	2
Antigen processing-Cross presentation	1
Toll Like Receptor 4 (TLR4) Cascade	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Class I MHC mediated antigen processing & presentation	1
Innate Immune System	1
Disease	1
Diseases of Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
protein binding	3
intracellular membrane-bounded organelle	3
cytoplasm	3
intracellular anatomical structure	2
sarcomere	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
heart contraction	1
regulation of blood circulation	1
midbrain development	1
neural nucleus development	1
signal transduction	1
blood vessel diameter maintenance	1
sprouting angiogenesis	1
positive regulation of angiogenesis	1
regulation of sprouting angiogenesis	1
metal ion binding	1
identical protein binding	1
protein dimerization activity	1
calcium ion binding	1
enzyme binding	1
binding	1
cation binding	1
nuclear lumen	1
endomembrane system	1
endoplasmic reticulum	1
sarcoplasm	1
I band	1
A band	1
cellular_component	1

Protein interactions and networks

STRING

2018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S100A1	ANXA2	P07355	947
S100A1	RYR2	Q92736	895
S100A1	S100B	P04271	814
S100A1	S100A7	P31151	808
S100A1	CALM1	P02593	765
S100A1	HRNR	Q86YZ3	733
S100A1	RYR1	P21817	732
S100A1	CAPZA1	P52907	689
S100A1	CALML3	P27482	688
S100A1	CALML6	Q8TD86	688
S100A1	CALML4	Q96GE6	688
S100A1	CALML5	Q9NZT1	688
S100A1	AGER	Q15109	678
S100A1	TLR4	O00206	669
S100A1	CAPZA2	P47755	665

IntAct

102 interactions, top by confidence:

A	B	Type	Score
S100A1	S100B	psi-mi:“MI:0915”(physical association)	0.970
S100B	S100A1	psi-mi:“MI:0915”(physical association)	0.970
S100A1	S100B	psi-mi:“MI:2364”(proximity)	0.970
S100A1	S100A1	psi-mi:“MI:0915”(physical association)	0.900
S100A1	S100A1	psi-mi:“MI:2364”(proximity)	0.900
S100A1	S100A1	psi-mi:“MI:0407”(direct interaction)	0.900
S100P	S100A1	psi-mi:“MI:0915”(physical association)	0.880

BioGRID (68): S100A1 (Two-hybrid), S100A2 (Two-hybrid), S100B (Two-hybrid), PLEKHF2 (Two-hybrid), S100P (Two-hybrid), S100A1 (Two-hybrid), NIF3L1 (Two-hybrid), S100B (Two-hybrid), S100A4 (Two-hybrid), S100B (Two-hybrid), FOPNL (Reconstituted Complex), S100A1 (Two-hybrid), S100B (Two-hybrid), S100A1 (Two-hybrid), BIK (Two-hybrid)

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: A6NMZ2, B7FF67, P02639, P23297, P35467, P56565, Q0P561, Q5RC36, Q7LZT1, Q8C9X1, A7K6Y9, O77691, O77791, P02632, P02633, P02634, P02638, P04271, P04631, P05942, P05964, P06702, P06703, P07091, P10462, P14069, P20930, P24480, P25815, P26447, P27003, P28318, P28783, P29034, P29377, P30801, P33763, P33764, P35466, P50114

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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
Cellular responses to stress	5	10.2×	2e-03
Cellular responses to stimuli	5	8.7×	2e-03
Innate Immune System	6	8.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

519 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153628497:G:GG	donor_gain	1.0000
1:153630659:GGAT:G	donor_gain	1.0000
1:153630660:G:GT	donor_gain	1.0000
1:153630660:GAT:G	donor_gain	1.0000
1:153630663:G:GG	donor_gain	1.0000
1:153628494:ACC:A	donor_gain	0.9900
1:153628494:ACCGT:A	donor_loss	0.9900
1:153628495:CC:C	donor_gain	0.9900
1:153628495:CCGTG:C	donor_loss	0.9900
1:153628496:CG:C	donor_loss	0.9900
1:153628497:G:GA	donor_loss	0.9900
1:153628498:TGAG:T	donor_loss	0.9900
1:153628499:GAG:G	donor_loss	0.9900
1:153628500:AG:A	donor_loss	0.9900
1:153630661:ATGT:A	donor_loss	0.9900
1:153630662:TGTG:T	donor_loss	0.9900
1:153630663:GTGA:G	donor_loss	0.9900
1:153630664:TGAG:T	donor_loss	0.9900
1:153630665:GAGCA:G	donor_loss	0.9900
1:153631695:CA:C	acceptor_loss	0.9900
1:153631696:A:AG	acceptor_gain	0.9900
1:153631696:A:AT	acceptor_loss	0.9900
1:153631697:G:GG	acceptor_gain	0.9900
1:153628492:CAACC:C	donor_gain	0.9800
1:153628493:AACC:A	donor_gain	0.9800
1:153629928:GA:G	donor_gain	0.9800
1:153630580:C:CA	acceptor_gain	0.9800
1:153630678:TG:T	donor_gain	0.9800
1:153630679:GG:G	donor_gain	0.9800
1:153631692:C:G	acceptor_gain	0.9800

AlphaMissense

626 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153630567:T:C	F16L	0.998
1:153630569:C:A	F16L	0.998
1:153630569:C:G	F16L	0.998
1:153631770:T:C	F72L	0.995
1:153631772:C:A	F72L	0.995
1:153631772:C:G	F72L	0.995
1:153630622:T:C	L34P	0.993
1:153630631:T:C	L37P	0.992
1:153630568:T:C	F16S	0.990
1:153631771:T:C	F72S	0.988
1:153631795:C:A	A80D	0.988
1:153630607:T:A	L29Q	0.986
1:153630607:T:C	L29P	0.985
1:153631771:T:G	F72C	0.984
1:153631797:G:C	A81P	0.984
1:153630543:G:C	A8P	0.983
1:153630567:T:A	F16I	0.983
1:153631777:A:T	E74V	0.983
1:153630544:C:A	A8E	0.982
1:153630556:T:C	L12P	0.982
1:153630579:T:C	S20P	0.981
1:153631744:A:T	D63V	0.980
1:153631743:G:C	D63H	0.979
1:153631794:G:C	A80P	0.978
1:153631801:T:C	L82P	0.978
1:153631804:C:A	T83K	0.978
1:153630567:T:G	F16V	0.977
1:153630568:T:G	F16C	0.977
1:153631779:T:G	Y75D	0.977
1:153630634:T:C	L38P	0.976

dbSNP variants (sampled 300 via entrez): RS1001120163 (1:153632245 A>G), RS1001530344 (1:153632397 G>A), RS1001587220 (1:153632503 C>T), RS1002348892 (1:153627471 C>G), RS1002873600 (1:153627293 C>T), RS1003089443 (1:153628698 C>A,T), RS1003648775 (1:153629946 T>A), RS1003874457 (1:153629021 T>G), RS1003919444 (1:153630268 C>T), RS1005872830 (1:153626643 G>A,T), RS1005955130 (1:153627718 A>C), RS1006155660 (1:153631462 A>T), RS1007313349 (1:153626440 C>T), RS1007608464 (1:153626707 C>A), RS1008172783 (1:153629093 C>T)

Disease associations

OMIM: gene MIM:176940 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
4-oxoretinoic acid	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression, affects reaction	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
jasplakinolide	affects expression, decreases reaction, affects localization	1
CGP 52608	affects binding, increases reaction	1
licochalcone B	increases expression	1
jinfukang	increases expression	1
Sunitinib	increases expression	1
Alitretinoin	decreases expression	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1
Malathion	decreases expression	1
Nickel	decreases expression	1
Oxygen	decreases expression	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tretinoin	decreases expression	1
Isotretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Gold Compounds	increases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B3S6	WAe009-A-73	Embryonic stem cell	Female

Clinical trials (associated diseases)

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