S100Z

Summary

S100Z (S100 calcium binding protein Z, HGNC:30367) is a protein-coding gene on chromosome 5q13.3, encoding Protein S100-Z (Q8WXG8).

Members of the S100 protein family contain 2 calcium-binding EF-hands and exhibit cell-type specific expression patterns. For additional background information on S100 proteins, see MIM 114085.

Source: NCBI Gene 170591 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_130772

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30367
Approved symbol	S100Z
Name	S100 calcium binding protein Z
Location	5q13.3
Locus type	gene with protein product
Status	Approved
Aliases	Gm625, S100-zeta
Ensembl gene	ENSG00000171643
Ensembl biotype	protein_coding
OMIM	610103
Entrez	170591

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000317593, ENST00000513010, ENST00000613039, ENST00000873722, ENST00000873723, ENST00000951781, ENST00000951782, ENST00000951783, ENST00000951784

RefSeq mRNA: 1 — MANE Select: NM_130772 NM_130772

CCDS: CCDS43333

Canonical transcript exons

ENST00000317593 — 5 exons

Exon	Start	End
ENSE00001257251	76875304	76875500
ENSE00001536985	76870166	76870284
ENSE00001557515	76877674	76877834
ENSE00002058011	76850014	76850155
ENSE00002078818	76920717	76921650

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 92.59.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4752 / max 107.5868, expressed in 254 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57157	0.9944	199
57159	0.2543	77
57158	0.1397	61
203593	0.0563	20
57160	0.0304	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	92.59	gold quality
leukocyte	CL:0000738	91.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.30	gold quality
granulocyte	CL:0000094	83.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.10	silver quality
oocyte	CL:0000023	76.53	gold quality
islet of Langerhans	UBERON:0000006	72.39	gold quality
blood	UBERON:0000178	71.22	gold quality
secondary oocyte	CL:0000655	70.65	silver quality
spleen	UBERON:0002106	69.26	gold quality
bone marrow cell	CL:0002092	66.60	silver quality
vermiform appendix	UBERON:0001154	66.24	gold quality
caecum	UBERON:0001153	60.60	gold quality
bone marrow	UBERON:0002371	59.06	gold quality
lower lobe of lung	UBERON:0008949	59.01	silver quality
lymph node	UBERON:0000029	58.32	gold quality
right lung	UBERON:0002167	57.66	gold quality
gall bladder	UBERON:0002110	57.17	gold quality
smooth muscle tissue	UBERON:0001135	54.49	gold quality
buccal mucosa cell	CL:0002336	53.94	gold quality
upper lobe of lung	UBERON:0008948	53.79	gold quality
upper lobe of left lung	UBERON:0008952	53.41	gold quality
pancreas	UBERON:0001264	53.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	52.61	gold quality
tonsil	UBERON:0002372	52.26	gold quality
small intestine Peyer’s patch	UBERON:0003454	51.60	gold quality
spinal cord	UBERON:0002240	51.46	gold quality
right coronary artery	UBERON:0001625	50.69	gold quality
small intestine	UBERON:0002108	50.33	gold quality
lung	UBERON:0002048	49.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

29 targeting S100Z, 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-3185	99.99	68.12	1959
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-320E	97.49	65.96	865
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-4535	97.27	65.17	469
HSA-MIR-8056	97.15	64.49	769
HSA-MIR-4448	97.04	66.22	752
HSA-MIR-3167	96.81	67.09	1236
HSA-MIR-4436B-5P	96.71	68.37	1346
HSA-MIR-6861-5P	96.23	67.19	800
HSA-MIR-1298-3P	94.05	64.84	620
HSA-MIR-10A-3P	93.57	64.43	451

Literature-anchored findings (GeneRIF, showing 1)

• Apo-S100Z has been compared to the structure of zebrafish calcium-S100Z with which it shares 70% sequence identity. It shows that the surface of interaction between the monomers in the dimers decreases; likewise, the surface among the dimers is lower, with the consequent absence of superhelical arrangement in the crystals. Also, calcium binding plays a fundamental role in triggering quaternary structure formation. (PMID:30710292)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	s100z	ENSDARG00000038729
mus_musculus	S100z	ENSMUSG00000021679
rattus_norvegicus	S100z	ENSRNOG00000078837

Paralogs (21): CRNN (ENSG00000143536), S100A8 (ENSG00000143546), S100A7 (ENSG00000143556), S100B (ENSG00000160307), S100A1 (ENSG00000160678), S100A11 (ENSG00000163191), S100A9 (ENSG00000163220), S100A12 (ENSG00000163221), S100P (ENSG00000163993), S100G (ENSG00000169906), 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-Z — Q8WXG8 (reviewed: Q8WXG8)

Alternative names: S100 calcium-binding protein Z

All UniProt accessions (1): Q8WXG8

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Homodimer. Interacts with S100P.

Tissue specificity. Highest level of expression in spleen and leukocytes.

Similarity. Belongs to the S-100 family.

RefSeq proteins (1): NP_570128* (*=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

Pfam: PF01023

UniProt features (22 total): binding site 9, helix 5, strand 2, domain 2, initiator methionine 1, chain 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5HYD	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXG8-F1	84.67	0.37

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 (9): 67; 69; 74; 20; 23; 28; 33; 63; 65

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GAZIN_EPIGENETIC_SILENCING_BY_KRAS, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_PROTEIN_HOMODIMERIZATION_ACTIVITY, GOMF_CALCIUM_DEPENDENT_PROTEIN_BINDING, MIKKELSEN_MCV6_ICP_WITH_H3K27ME3, ARID5B_TARGET_GENES, E2F5_TARGET_GENES, MAFG_TARGET_GENES, MEF2D_TARGET_GENES, NFE2L1_TARGET_GENES, PHB2_TARGET_GENES, ZNF175_TARGET_GENES, ZNF589_TARGET_GENES, ZNF592_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (6): calcium ion binding (GO:0005509), protein homodimerization activity (GO:0042803), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515), identical protein binding (GO:0042802), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
metal ion binding	1
identical protein binding	1
protein dimerization activity	1
calcium ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

1051 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S100Z	HRNR	Q86YZ3	697
S100Z	S100A13	Q99584	671
S100Z	S100A7L2	Q5SY68	583
S100Z	S100A7A	Q86SG5	573
S100Z	RPTN	Q6XPR3	571
S100Z	S100A7	P31151	571
S100Z	S100A14	Q9HCY8	541
S100Z	KRTAP17-1	Q9BYP8	495
S100Z	TCHHL1	Q5QJ38	450
S100Z	RNF128	Q8TEB7	415
S100Z	TCHH	Q07283	399
S100Z	CALU	O43852	396
S100Z	SLC39A14	Q15043	384
S100Z	BTNL2	Q9UIR0	383
S100Z	ADCYAP1	P18509	369

IntAct

41 interactions, top by confidence:

A	B	Type	Score
OIP5	S100Z	psi-mi:“MI:0915”(physical association)	0.560
SNAPC5	S100Z	psi-mi:“MI:0915”(physical association)	0.560
S100Z	RBM48	psi-mi:“MI:0915”(physical association)	0.560
S100A3	S100Z	psi-mi:“MI:0915”(physical association)	0.560
S100B	S100Z	psi-mi:“MI:0915”(physical association)	0.560
S100P	S100Z	psi-mi:“MI:0915”(physical association)	0.560
S100A1	S100Z	psi-mi:“MI:0915”(physical association)	0.560
S100A10	S100Z	psi-mi:“MI:0915”(physical association)	0.560
RASSF2	S100Z	psi-mi:“MI:0915”(physical association)	0.560
BEX3	S100Z	psi-mi:“MI:0915”(physical association)	0.560
RBM48	S100Z	psi-mi:“MI:0915”(physical association)	0.560
S100Z	SLC8A1	psi-mi:“MI:0407”(direct interaction)	0.440
S100A3	S100Z	psi-mi:“MI:0915”(physical association)	0.000
S100Z	S100B	psi-mi:“MI:0915”(physical association)	0.000
S100P	S100Z	psi-mi:“MI:0915”(physical association)	0.000
S100A1	S100Z	psi-mi:“MI:0915”(physical association)	0.000
BEX3	S100Z	psi-mi:“MI:0915”(physical association)	0.000
S100A10	S100Z	psi-mi:“MI:0915”(physical association)	0.000
S100Z	S100A10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): S100Z (Two-hybrid), S100Z (Two-hybrid), S100Z (Two-hybrid), S100Z (Two-hybrid), S100Z (Two-hybrid), S100Z (Two-hybrid), S100Z (Two-hybrid), SNAPC5 (Two-hybrid), S100A3 (Two-hybrid), S100A10 (Two-hybrid), S100Z (Two-hybrid), S100Z (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, O77791, P02632, P02633, P02634, P22793, P24480, P29377, P31151, P31725, P50116, P50117, P79105, P80511, P97816, Q14ST5, Q28050, Q503K9, Q6S5I3, Q865V3, Q86SG5, Q8WXG8, O77691, P05964, P06703, P14069, P28318, P30801, P62818, P62819, Q2EN75, P02638, P02639, P04271, P04631, P05942, P06702, P07091, P10462

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1028 predictions. Top by Δscore:

Variant	Effect	Δscore
5:76875292:ATTCT:A	acceptor_gain	1.0000
5:76875296:T:TA	acceptor_gain	1.0000
5:76875301:AAGT:A	acceptor_gain	1.0000
5:76875302:A:G	acceptor_gain	1.0000
5:76875315:C:CA	acceptor_gain	1.0000
5:76875316:G:A	acceptor_gain	1.0000
5:76875322:G:A	acceptor_gain	1.0000
5:76875324:T:TA	acceptor_gain	1.0000
5:76850142:G:GT	donor_gain	0.9900
5:76850150:TCTA:T	donor_gain	0.9900
5:76850151:CTAAG:C	donor_loss	0.9900
5:76850152:TAAGG:T	donor_loss	0.9900
5:76850154:AG:A	donor_loss	0.9900
5:76850449:T:TA	acceptor_gain	0.9900
5:76870165:GT:G	acceptor_gain	0.9900
5:76875287:T:TA	acceptor_gain	0.9900
5:76875292:A:AG	acceptor_gain	0.9900
5:76875293:T:G	acceptor_gain	0.9900
5:76875301:A:AG	acceptor_gain	0.9900
5:76875321:T:A	acceptor_gain	0.9900
5:76875325:G:A	acceptor_gain	0.9900
5:76875497:CTCGG:C	donor_loss	0.9900
5:76875499:CGGTG:C	donor_loss	0.9900
5:76875500:GGT:G	donor_loss	0.9900
5:76875501:GT:G	donor_loss	0.9900
5:76875502:T:A	donor_loss	0.9900
5:76850149:GTC:G	donor_gain	0.9800
5:76850151:CTAA:C	donor_gain	0.9800
5:76850152:TAAG:T	donor_gain	0.9800
5:76853982:T:A	acceptor_gain	0.9800

AlphaMissense

662 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:76877755:T:C	F75L	0.863
5:76877757:C:A	F75L	0.863
5:76877757:C:G	F75L	0.863
5:76875405:T:C	F16L	0.846
5:76875407:C:A	F16L	0.846
5:76875407:C:G	F16L	0.846
5:76877746:T:C	F72L	0.819
5:76877748:T:A	F72L	0.819
5:76877748:T:G	F72L	0.819
5:76875492:T:C	F45L	0.787
5:76875494:C:A	F45L	0.787
5:76875494:C:G	F45L	0.787
5:76877800:T:C	F90L	0.716
5:76877802:T:A	F90L	0.716
5:76877802:T:G	F90L	0.716
5:76875438:T:C	F27L	0.651
5:76875440:C:A	F27L	0.651
5:76875440:C:G	F27L	0.651

dbSNP variants (sampled 300 via entrez): RS1000046815 (5:76919902 C>T), RS1000054257 (5:76889227 T>C), RS1000179105 (5:76866003 A>T), RS1000246505 (5:76913947 G>T), RS1000268652 (5:76871445 A>G), RS1000300153 (5:76938077 G>A), RS1000301335 (5:76897368 A>T), RS1000304970 (5:76943477 T>G), RS1000326286 (5:76861051 A>G), RS1000334222 (5:76897470 A>G), RS1000358240 (5:76943123 G>C), RS1000359168 (5:76901132 G>A,T), RS1000370313 (5:76852499 C>A), RS1000422760 (5:76852880 T>A), RS1000426186 (5:76949569 G>A,T)

Disease associations

OMIM: gene MIM:610103 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009267_8	Dental caries (decayed, missing and filled teeth)	1.000000e-06
GCST009268_10	Dental caries (decayed, missing and filled tooth surfaces)	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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