STATH

Summary

STATH (statherin, HGNC:11369) is a protein-coding gene on chromosome 4q13.3, encoding Statherin (P02808). Salivary protein that stabilizes saliva supersaturated with calcium salts by inhibiting the precipitation of calcium phosphate salts.

Predicted to enable extracellular matrix constituent, lubricant activity and hydroxyapatite binding activity. Predicted to be a structural constituent of tooth enamel. Predicted to be involved in negative regulation of bone mineralization; ossification; and saliva secretion. Predicted to be located in extracellular region.

Source: NCBI Gene 6779 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_003154

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11369
Approved symbol	STATH
Name	statherin
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	STR
Ensembl gene	ENSG00000126549
Ensembl biotype	protein_coding
OMIM	184470
Entrez	6779

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 retained_intron, 2 protein_coding

ENST00000246895, ENST00000381060, ENST00000506576, ENST00000507211, ENST00000507962, ENST00000510010, ENST00000511658

RefSeq mRNA: 2 — MANE Select: NM_003154 NM_001009181, NM_003154

CCDS: CCDS33998, CCDS3533

Canonical transcript exons

ENST00000246895 — 6 exons

Exon	Start	End
ENSE00000865220	69999780	69999809
ENSE00000865221	70000863	70000982
ENSE00001024589	69995966	69996025
ENSE00002020099	70002189	70002570
ENSE00003601159	69999667	69999687
ENSE00003617254	69998423	69998488

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 99.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1206.3629 / max 1229925.5410, expressed in 105 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47853	1195.8798	99
47857	5.4695	17
203193	4.3686	20
47858	0.2429	7
47851	0.2390	10
47854	0.0958	3
47850	0.0404	3
47849	0.0153	3
47852	0.0116	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	99.97	gold quality
saliva-secreting gland	UBERON:0001044	95.51	gold quality
minor salivary gland	UBERON:0001830	95.07	gold quality
tonsil	UBERON:0002372	86.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.83	gold quality
placenta	UBERON:0001987	67.23	gold quality
bone marrow	UBERON:0002371	58.52	gold quality
bone marrow cell	CL:0002092	50.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	48.10	silver quality
skeletal muscle tissue	UBERON:0001134	46.13	gold quality
lower esophagus mucosa	UBERON:0035834	44.62	silver quality
hindlimb stylopod muscle	UBERON:0004252	43.65	gold quality
urinary bladder	UBERON:0001255	42.26	gold quality
muscle tissue	UBERON:0002385	42.15	gold quality
mucosa of stomach	UBERON:0001199	39.60	silver quality
right lobe of liver	UBERON:0001114	39.45	gold quality
esophagus mucosa	UBERON:0002469	38.87	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
liver	UBERON:0002107	37.12	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
descending thoracic aorta	UBERON:0002345	36.33	gold quality
sural nerve	UBERON:0015488	35.86	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
adenohypophysis	UBERON:0002196	34.89	gold quality
gastrocnemius	UBERON:0001388	34.06	gold quality
right lung	UBERON:0002167	33.88	gold quality
pituitary gland	UBERON:0000007	33.76	gold quality
muscle of leg	UBERON:0001383	33.67	gold quality
esophagus	UBERON:0001043	33.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

25 targeting STATH, 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-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-3689F	98.35	70.08	1052
HSA-MIR-192-3P	97.52	67.66	1001

Literature-anchored findings (GeneRIF, showing 13)

• dOgg1 and RpS3 in mitochondria increase cell survival after exposure to the nitric oxide donor SNAP (PMID:16895796)
• Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status. (PMID:34914692)
• RpS3 Is Required for Spermatogenesis of Drosophila melanogaster. (PMID:36831240)
• inhibits calcium phosphate precipitation (PMID:12060866)
• results suggest that a layer rich in statherin forms at the interface of saliva and air, and that the surface rheology developed is dependent upon protein interactions mediated by calcium (PMID:15769251)
• insight into the molecular interactions of statherin with hydroxyapatite surfaces (PMID:19678690)
• In conclusion, statherin induces transition to yeast of Candida albicans hyphae and may thus contribute to the oral defense against candidiasis. (PMID:19799638)
• Data show that the full characterization of the statherin peptides generated facilitates the elucidation of their novel functional roles in the oral and gastro-intestinal environment. (PMID:20731414)
• phenylalanine orientations in statherin bound to hydroxyapatite surfaces (PMID:22563672)
• effects of statherin on intracellular calcium level and its subsequent related molecular alterations would give us new pathogenic aspect in oral carcinogenesis (PMID:25128293)
• The total protein and statherin in the in-vivo AEP were different between eroded and non-eroded tooth surfaces of the same patient (PMID:28837608)
• A negative screening of rare genetic variants in the ADIPOQ and STATH genes in cystic fibrosis. (PMID:31606405)
• Statherin and alpha-amylase levels in saliva from patients with gingivitis and periodontitis. (PMID:36395562)

Cross-species orthologs

0 orthologs

Paralogs (2): HTN1 (ENSG00000126550), HTN3 (ENSG00000205649)

Protein

Protein identifiers

Statherin — P02808 (reviewed: P02808)

All UniProt accessions (1): P02808

UniProt curated annotations — full annotation on UniProt →

Function. Salivary protein that stabilizes saliva supersaturated with calcium salts by inhibiting the precipitation of calcium phosphate salts. It also modulates hydroxyapatite crystal formation on the tooth surface.

Subcellular location. Secreted.

Tissue specificity. Secreted by parotid and submandibular glands.

Post-translational modifications. Substrate for transglutaminase-2. More than 95% of the cyclized peptide is cyclo-statherin Q-37, and less than 5% is cyclo-statherin Q-39. Cyclized forms account for about 1% of total statherin in saliva. Sulfated on tyrosine residues.

Similarity. Belongs to the histatin/statherin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P02808-1	1	yes
P02808-2	2

RefSeq proteins (2): NP_001009181, NP_003145* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005575	Statherin	Family
IPR030773	Histatin/statherin	Family

Pfam: PF03875

UniProt features (10 total): region of interest 2, modified residue 2, cross-link 2, signal peptide 1, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02808-F1	63.26	0.03

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 21, 22, 25–58, 25–56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GOBP_DIGESTION, MODULE_92, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, chr4q13, DAVICIONI_RHABDOMYOSARCOMA_PAX_FOXO1_FUSION_UP, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, MODULE_379, GOBP_BONE_MINERALIZATION, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_SECRETION, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_DIGESTIVE_SYSTEM_PROCESS, CAR_MLANA, GOBP_OSSIFICATION

GO Biological Process (6): ossification (GO:0001503), negative regulation of bone mineralization (GO:0030502), biomineral tissue development (GO:0031214), defense response to bacterium (GO:0042742), saliva secretion (GO:0046541), regulation of bone mineralization (GO:0030500)

GO Molecular Function (4): extracellular matrix constituent, lubricant activity (GO:0030197), structural constituent of tooth enamel (GO:0030345), hydroxyapatite binding (GO:0046848), protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
bone mineralization	2
multicellular organismal process	1
negative regulation of ossification	1
regulation of bone mineralization	1
negative regulation of biomineral tissue development	1
tissue development	1
animal organ development	1
defense response	1
response to bacterium	1
body fluid secretion	1
digestive system process	1
secretion by tissue	1
regulation of ossification	1
regulation of biomineral tissue development	1
extracellular matrix structural constituent	1
extracellular matrix structural constituent conferring compression resistance	1
small molecule binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STATH	HTN1	P15515	991
STATH	MUC5B	Q9HC84	935
STATH	HTN3	P15516	919
STATH	MUC7	Q8TAX7	911
STATH	C4BPA	P04003	774
STATH	CST4	P01036	773
STATH	PRPF3	O43395	678
STATH	SMR3B	P02814	621
STATH	PRR4	Q16378	620
STATH	ALB	P02768	608
STATH	LTF	P02788	600
STATH	CTRC	Q99895	588
STATH	PRB2	P02811	582
STATH	PRB1	P04280	581
STATH	CST1	P01037	580

IntAct

81 interactions, top by confidence:

A	B	Type	Score
STATH	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
STATH	KCNJ6	psi-mi:“MI:0915”(physical association)	0.560
LEUTX	STATH	psi-mi:“MI:0915”(physical association)	0.560
STATH	FIMP	psi-mi:“MI:0915”(physical association)	0.560
STATH	TMEM80	psi-mi:“MI:0915”(physical association)	0.560
STATH	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
STATH	MFSD5	psi-mi:“MI:0915”(physical association)	0.560
STATH	TMX2	psi-mi:“MI:0915”(physical association)	0.560
STATH	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
STATH	FCRL3	psi-mi:“MI:0915”(physical association)	0.560
STATH	AQP6	psi-mi:“MI:0915”(physical association)	0.560
GPR42	STATH	psi-mi:“MI:0915”(physical association)	0.560
STATH	SPNS3	psi-mi:“MI:0915”(physical association)	0.560
STATH	MRM1	psi-mi:“MI:0915”(physical association)	0.560
STATH	DERL3	psi-mi:“MI:0915”(physical association)	0.560
STATH	TFAM	psi-mi:“MI:0915”(physical association)	0.560
STATH	SLC10A6	psi-mi:“MI:0915”(physical association)	0.560
STATH	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
STATH	SLC39A2	psi-mi:“MI:0915”(physical association)	0.560
STATH	MTIF3	psi-mi:“MI:0915”(physical association)	0.560
STATH	GPR152	psi-mi:“MI:0915”(physical association)	0.560
STATH	REEP4	psi-mi:“MI:0915”(physical association)	0.560
SGPL1	STATH	psi-mi:“MI:0915”(physical association)	0.560
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
NEFM	VWA8	psi-mi:“MI:0914”(association)	0.530
MUC7	STATH	psi-mi:“MI:0915”(physical association)	0.510
STATH	MUC7	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (60): STATH (Affinity Capture-MS), STATH (Affinity Capture-MS), STATH (Affinity Capture-MS), STATH (Two-hybrid), STATH (Two-hybrid), STATH (Two-hybrid), STATH (Two-hybrid), STATH (Two-hybrid), STATH (Two-hybrid), STATH (Two-hybrid), SLC10A6 (Two-hybrid), TMEM56 (Two-hybrid), KCNJ6 (Two-hybrid), FCRL3 (Two-hybrid), SLC39A2 (Two-hybrid)

ESM2 similar proteins: A0A0G2K6Z9, A0A411D538, A0A8U0LTF0, A0A8U0LTF5, A1YQ92, A6RPX6, B3SVF0, B3SVF1, B9UIU9, C4R2P5, C5M3K2, D5L5Q7, D6QY17, E6R3N7, H2A0N6, H7CE70, O18417, O46199, O76192, P02808, P0DQP3, P0DXT2, P0DXT4, P0DXT5, P0DXT6, P15450, P36193, P60985, P86965, Q09283, Q1A3Q6, Q24395, Q299E6, Q3V2T4, Q42465, Q52MQ7, Q8HY86, Q8MJ39, Q8NFU4, Q95WA3

Diamond homologs: P02808, Q8HY86, P15515, P15516

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

577 predictions. Top by Δscore:

Variant	Effect	Δscore
4:69998422:GA:G	acceptor_gain	1.0000
4:69998485:GATT:G	donor_gain	1.0000
4:69998489:G:GG	donor_gain	1.0000
4:69999663:TAAGG:T	acceptor_loss	1.0000
4:69999664:A:AG	acceptor_gain	1.0000
4:69999664:AAG:A	acceptor_gain	1.0000
4:69999665:A:G	acceptor_gain	1.0000
4:69999666:GG:G	acceptor_loss	1.0000
4:70000850:T:A	acceptor_gain	1.0000
4:70000862:GT:G	acceptor_gain	1.0000
4:70000862:GTAT:G	acceptor_gain	1.0000
4:69998421:A:AG	acceptor_gain	0.9900
4:69998422:G:GG	acceptor_gain	0.9900
4:69998422:GAGA:G	acceptor_gain	0.9900
4:69998486:ATT:A	donor_gain	0.9900
4:69998486:ATTG:A	donor_loss	0.9900
4:69998487:TT:T	donor_gain	0.9900
4:69998488:TGT:T	donor_loss	0.9900
4:69998489:GTAA:G	donor_loss	0.9900
4:69998490:T:TC	donor_loss	0.9900
4:69998491:A:AC	donor_loss	0.9900
4:69998492:AGTAT:A	donor_loss	0.9900
4:69999664:AAGG:A	acceptor_gain	0.9900
4:69999666:GGGA:G	acceptor_gain	0.9900
4:69999688:G:GG	donor_gain	0.9900
4:69999688:GTG:G	donor_loss	0.9900
4:69999689:T:G	donor_loss	0.9900
4:69999808:GT:G	donor_gain	0.9900
4:69999810:G:GG	donor_gain	0.9900
4:70000852:T:TA	acceptor_gain	0.9900

AlphaMissense

396 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:69998475:T:G	M13R	0.981
4:69998457:C:A	A7D	0.974
4:69999674:A:T	D20V	0.974
4:69998469:C:A	A11D	0.972
4:69998475:T:A	M13K	0.971
4:69999673:G:C	D20H	0.969
4:69999674:A:C	D20A	0.964
4:69999686:A:T	E24V	0.959
4:69998485:G:A	M16I	0.954
4:69998485:G:C	M16I	0.954
4:69998485:G:T	M16I	0.954
4:69999675:T:A	D20E	0.954
4:69999675:T:G	D20E	0.954
4:69999683:A:T	E23V	0.954
4:69999673:G:T	D20Y	0.952
4:69998463:T:A	I9N	0.947
4:69998472:T:C	L12P	0.947
4:69999674:A:G	D20G	0.947
4:69999676:T:C	S21P	0.946
4:69998451:T:A	V5D	0.937
4:69998478:T:A	V14D	0.937
4:69998484:T:A	M16K	0.936
4:69998484:T:G	M16R	0.934
4:69998472:T:A	L12H	0.933
4:69998472:T:G	L12R	0.926
4:69999686:A:C	E24A	0.916
4:69998487:T:A	I17N	0.908
4:69999671:C:T	A19V	0.901
4:69999673:G:A	D20N	0.899
4:69998448:T:A	L4H	0.897

dbSNP variants (sampled 300 via entrez): RS1000946693 (4:69996501 TAA>T), RS1001009769 (4:70001953 A>C,G), RS1001206895 (4:69999116 A>G), RS1002155519 (4:69997514 G>A,C), RS1002377332 (4:69997359 A>T), RS1002702990 (4:69996155 A>G,T), RS1002758504 (4:69996564 C>G), RS1002825195 (4:70000245 T>A,G), RS1002859806 (4:70002175 T>C), RS10031583 (4:70002868 T>A,C,G), RS1003548684 (4:70000530 A>T), RS1003927055 (4:69995865 A>T), RS1003982931 (4:70001877 G>T), RS1004056572 (4:70001575 G>A), RS1004058820 (4:69994370 A>C)

Disease associations

OMIM: gene MIM:184470 | 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

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
Arsenic Trioxide	decreases expression	1
Allergens	increases expression	1
Aluminum Oxide	increases expression	1
Arsenicals	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Potassium Dichromate	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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