OSTF1

Summary

OSTF1 (osteoclast stimulating factor 1, HGNC:8510) is a protein-coding gene on chromosome 9q21.13, encoding Osteoclast-stimulating factor 1 (Q92882). Induces bone resorption, acting probably through a signaling cascade which results in the secretion of factor(s) enhancing osteoclast formation and activity.

Osteoclast-stimulating factor-1 is an intracellular protein produced by osteoclasts that indirectly induces osteoclast formation and bone resorption (Reddy et al., 1998 [PubMed 10092216]).

Source: NCBI Gene 26578 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_012383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8510
Approved symbol	OSTF1
Name	osteoclast stimulating factor 1
Location	9q21.13
Locus type	gene with protein product
Status	Approved
Aliases	SH3P2, OSF, bA235O14.1
Ensembl gene	ENSG00000134996
Ensembl biotype	protein_coding
OMIM	610180
Entrez	26578

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000346234, ENST00000857341, ENST00000857342, ENST00000857343, ENST00000857344, ENST00000857345, ENST00000857346, ENST00000857347, ENST00000857348, ENST00000934388, ENST00000934389, ENST00000947040, ENST00000947041

RefSeq mRNA: 1 — MANE Select: NM_012383 NM_012383

CCDS: CCDS6651

Canonical transcript exons

ENST00000346234 — 10 exons

Exon	Start	End
ENSE00000707172	75130578	75130641
ENSE00000707175	75133294	75133401
ENSE00000803850	75131770	75131823
ENSE00000803852	75134346	75134395
ENSE00000803853	75137538	75137616
ENSE00000803854	75140834	75140932
ENSE00001023928	75117504	75117550
ENSE00001198580	75146683	75147265
ENSE00001198586	75127569	75127619
ENSE00001428405	75088514	75088726

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 98.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.8273 / max 937.0324, expressed in 1815 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96980	46.6743	1814
96979	10.1123	1732
96978	1.3690	919
96977	0.6717	434

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.58	gold quality
mononuclear cell	CL:0000842	98.23	gold quality
leukocyte	CL:0000738	98.21	gold quality
lower esophagus mucosa	UBERON:0035834	97.79	gold quality
granulocyte	CL:0000094	97.29	gold quality
esophagus mucosa	UBERON:0002469	97.06	gold quality
blood	UBERON:0000178	96.13	gold quality
right lung	UBERON:0002167	96.07	gold quality
skin of abdomen	UBERON:0001416	95.00	gold quality
spleen	UBERON:0002106	94.96	gold quality
upper lobe of left lung	UBERON:0008952	94.83	gold quality
skin of leg	UBERON:0001511	94.80	gold quality
gall bladder	UBERON:0002110	94.80	gold quality
rectum	UBERON:0001052	94.74	gold quality
buccal mucosa cell	CL:0002336	94.60	gold quality
esophagus squamous epithelium	UBERON:0006920	94.50	gold quality
mucosa of transverse colon	UBERON:0004991	94.06	gold quality
epithelium of esophagus	UBERON:0001976	93.98	gold quality
upper lobe of lung	UBERON:0008948	93.71	gold quality
omental fat pad	UBERON:0010414	93.67	gold quality
peritoneum	UBERON:0002358	93.59	gold quality
zone of skin	UBERON:0000014	93.22	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.80	gold quality
esophagus	UBERON:0001043	92.58	gold quality
lymph node	UBERON:0000029	92.50	gold quality
minor salivary gland	UBERON:0001830	92.38	gold quality
vermiform appendix	UBERON:0001154	92.25	gold quality
islet of Langerhans	UBERON:0000006	92.10	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.92	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	22.42
E-MTAB-8410	yes	13.28
E-MTAB-9388	yes	10.34
E-MTAB-8498	yes	9.05
E-MTAB-7606	no	482.88
E-GEOD-110499	no	400.37
E-MTAB-5061	no	3.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting OSTF1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4470	99.66	69.35	1767

Literature-anchored findings (GeneRIF, showing 6)

• SH3P2, a novel component of adhesion sites, is involved in Cbl and Src-mediated pathways (PMID:15135048)
• Crystals of human osteoclast-stimulating factor were obtained by the hanging-drop vapour-diffusion method using X ray crystallography. (PMID:16508112)
• The SH3 domain structure of osteoclast stimulating factor at atomic resolution provides an accurate framework for structure-based design of its inhibitors. (PMID:16946461)
• The peptide-binding groove of OSTF-SH3 domain adopts a conformation different from other SH3 domains and probably needs a conformational switch for binding to its proline-rich ligand; this status is possibly regulated by the C-terminal ankyrin repeats. (PMID:19137598)
• Data show that SH3P2 was phosphorylated on Ser(202) by ribosomal S6 kinase (RSK) in an ERK pathway-dependent manner, and such phosphorylation inhibited the ability of SH3P2 to suppress cell motility. (PMID:21501342)
• We utilized a structure-based approach to pinpoint the binding interface to a strictly conserved cluster of residues on the surface of RP2 that spans both the C- and N-terminal domains of the protein, and which is structurally distinct from the ARL3-binding site.RP2 is a positive regulator of cell motility in vitro, recruiting OSTF1 to the cell membrane and preventing its interaction with the migration regulator Myo1E. (PMID:29361551)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ostf1	ENSDARG00000091555
mus_musculus	Ostf1	ENSMUSG00000024725
rattus_norvegicus	Ostf1	ENSRNOG00000012156
drosophila_melanogaster	ckn	FBGN0033987
drosophila_melanogaster	CG44838	FBGN0266101
caenorhabditis_elegans	Y106G6H.14	WBGENE00013724

Protein

Protein identifiers

Osteoclast-stimulating factor 1 — Q92882 (reviewed: Q92882)

All UniProt accessions (1): Q92882

UniProt curated annotations — full annotation on UniProt →

Function. Induces bone resorption, acting probably through a signaling cascade which results in the secretion of factor(s) enhancing osteoclast formation and activity.

Subunit / interactions. Interacts with SRC and SMN1. Interacts with FASLG.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitously expressed. Present in osteoclasts (at protein level).

Domain organisation. The SH3 domain mediates interaction with SMN1.

RefSeq proteins (1): NP_036515* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00018, PF12796

UniProt features (29 total): helix 9, strand 6, modified residue 4, repeat 3, sequence variant 2, sequence conflict 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1ZLM	X-RAY DIFFRACTION	1.07
3EHR	X-RAY DIFFRACTION	1.95
3EHQ	X-RAY DIFFRACTION	2.57
1X2K	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92882-F1	90.42	0.84

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): 2, 200, 202, 213

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 187 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_MSN, GOCC_SECRETORY_GRANULE, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, RIZKI_TUMOR_INVASIVENESS_3D_DN, DAVICIONI_RHABDOMYOSARCOMA_PAX_FOXO1_FUSION_UP, RICKMAN_METASTASIS_DN, GNF2_MYD88, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, GOBP_OSSIFICATION, ABBUD_LIF_SIGNALING_1_DN, GNF2_CD97, BRACHAT_RESPONSE_TO_METHOTREXATE_DN

GO Biological Process (2): ossification (GO:0001503), signal transduction (GO:0007165)

GO Molecular Function (2): SH3 domain binding (GO:0017124), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), secretory granule lumen (GO:0034774), ficolin-1-rich granule lumen (GO:1904813), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
multicellular organismal process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein domain specific binding	1
binding	1
secretory granule	1
cytoplasmic vesicle lumen	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1533 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSTF1	CPZ	Q66K79	644
OSTF1	POLI	Q9UNA4	529
OSTF1	SIRPA	P78324	500
OSTF1	SRC	P12931	482
OSTF1	H1-1	Q02539	471
OSTF1	BECN1	Q14457	444
OSTF1	H1-5	P16401	434
OSTF1	RPS6KA1	Q15418	417
OSTF1	RPS6KA3	P51812	407
OSTF1	RPS6KA2	Q15349	405
OSTF1	HNF1A	P20823	401
OSTF1	CORO1B	Q9BR76	391
OSTF1	ACTR8	Q9H981	382
OSTF1	PDCD5	O14737	376
OSTF1	RNF141	Q8WVD5	375

IntAct

59 interactions, top by confidence:

A	B	Type	Score
OSTF1	RP2	psi-mi:“MI:0914”(association)	0.640
MYO1F	OSTF1	psi-mi:“MI:0915”(physical association)	0.590
SMN1	OSTF1	psi-mi:“MI:0407”(direct interaction)	0.590
SMN1	OSTF1	psi-mi:“MI:0915”(physical association)	0.590
OSTF1	SMN1	psi-mi:“MI:0915”(physical association)	0.590
SDCBP	OSTF1	psi-mi:“MI:0915”(physical association)	0.560
EFS	OSTF1	psi-mi:“MI:0915”(physical association)	0.560
REL	OSTF1	psi-mi:“MI:0915”(physical association)	0.560
OSTF1	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
OSTF1	REL	psi-mi:“MI:0915”(physical association)	0.560
TRIM54	OSTF1	psi-mi:“MI:0915”(physical association)	0.560
ADAM15	OSTF1	psi-mi:“MI:0407”(direct interaction)	0.560
HTT	OSTF1	psi-mi:“MI:0915”(physical association)	0.550
OSTF1	HTT	psi-mi:“MI:0915”(physical association)	0.550
TMEM185A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
POP4	NME2P1	psi-mi:“MI:0914”(association)	0.530
OSTF1	CHMP2A	psi-mi:“MI:0914”(association)	0.530
ADAM8	OSTF1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (130): OSTF1 (Two-hybrid), OSTF1 (Two-hybrid), OSTF1 (Two-hybrid), TRIM54 (Two-hybrid), OSTF1 (Affinity Capture-MS), OSTF1 (Affinity Capture-MS), OSTF1 (Co-fractionation), OSTF1 (Co-fractionation), OSTF1 (Two-hybrid), RP2 (Affinity Capture-MS), OSTF1 (Affinity Capture-MS), KLHL42 (Affinity Capture-MS), OSTF1 (Affinity Capture-MS), MYO1E (Affinity Capture-MS), OSTF1 (Affinity Capture-MS)

ESM2 similar proteins: A8XI74, F1N9Y5, G5ECJ6, O15075, P08487, P08630, P10686, P16885, P19174, P24135, P24604, P35991, P42680, P43403, P43404, P43405, P46108, P46109, P47941, P48025, P51813, P53356, P54936, P87378, Q00655, Q04929, Q06187, Q22070, Q24145, Q45FX5, Q54Y55, Q5U2U2, Q62077, Q62422, Q63768, Q64010, Q64725, Q6P686, Q6TGW5, Q6XJU9

Diamond homologs: A1CEK6, A1DFN5, A1DFP5, A2QW93, A2QWA2, A3LXQ8, A4FU49, A4RF61, A6QLK6, B0BNA1, F4KAU9, O08641, O14964, O35179, O35180, O35413, O35964, O43125, O74749, O80910, O94875, P07751, P0CR78, P0CR79, P10569, P19878, P29355, P38753, P62993, P62994, P87379, Q06449, Q07883, Q08012, Q0CJU8, Q0CJV3, Q0U4Z8, Q0U6X7, Q0V8S0, Q15080

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS6KA1	“down-regulates activity”	OSTF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of canonical NF-kappaB signal transduction	5	8.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1465 predictions. Top by Δscore:

Variant	Effect	Δscore
9:75117546:GAACT:G	donor_gain	1.0000
9:75117551:G:GG	donor_gain	1.0000
9:75130576:A:AG	acceptor_gain	1.0000
9:75130576:A:C	acceptor_loss	1.0000
9:75130576:AGAGC:A	acceptor_gain	1.0000
9:75130577:G:GG	acceptor_gain	1.0000
9:75130577:GA:G	acceptor_gain	1.0000
9:75130577:GAGC:G	acceptor_gain	1.0000
9:75130577:GAGCG:G	acceptor_gain	1.0000
9:75130639:ATGGT:A	donor_loss	1.0000
9:75130640:TGGTA:T	donor_loss	1.0000
9:75130641:GGTAA:G	donor_loss	1.0000
9:75130642:G:C	donor_loss	1.0000
9:75130642:G:GG	donor_gain	1.0000
9:75130643:T:TC	donor_loss	1.0000
9:75131768:A:AG	acceptor_gain	1.0000
9:75131769:G:GG	acceptor_gain	1.0000
9:75131769:GT:G	acceptor_gain	1.0000
9:75134341:TTCA:T	acceptor_loss	1.0000
9:75134342:TCAG:T	acceptor_loss	1.0000
9:75134343:CAGAT:C	acceptor_loss	1.0000
9:75134344:A:AG	acceptor_gain	1.0000
9:75134344:A:T	acceptor_loss	1.0000
9:75134345:G:GG	acceptor_gain	1.0000
9:75134345:GAT:G	acceptor_gain	1.0000
9:75134345:GATAT:G	acceptor_gain	1.0000
9:75134392:GCAG:G	donor_gain	1.0000
9:75134394:AGGTA:A	donor_loss	1.0000
9:75134396:GTA:G	donor_loss	1.0000
9:75134397:T:A	donor_loss	1.0000

AlphaMissense

1409 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:75133350:G:C	D103H	0.999
9:75133351:A:T	D103V	0.999
9:75133383:T:C	C114R	0.999
9:75133384:G:A	C114Y	0.999
9:75133385:C:G	C114W	0.999
9:75137540:C:A	N137K	0.999
9:75137540:C:G	N137K	0.999
9:75137569:C:A	A147D	0.999
9:75130599:G:C	G52R	0.998
9:75130600:G:A	G52D	0.998
9:75131811:G:C	A80P	0.998
9:75131814:G:C	A81P	0.998
9:75131815:C:A	A81E	0.998
9:75133294:G:T	G84V	0.998
9:75133317:T:C	C92R	0.998
9:75133319:T:G	C92W	0.998
9:75133350:G:T	D103Y	0.998
9:75133351:A:C	D103A	0.998
9:75137572:C:A	A148D	0.998
9:75137605:T:C	L159P	0.998
9:75140856:C:A	N170K	0.998
9:75140856:C:G	N170K	0.998
9:75131812:C:A	A80E	0.997
9:75131819:A:C	K82N	0.997
9:75131819:A:T	K82N	0.997
9:75133369:C:A	A109D	0.997
9:75133381:C:A	A113D	0.997
9:75134361:T:C	L125P	0.997
9:75137539:A:T	N137I	0.997
9:75137571:G:C	A148P	0.997

dbSNP variants (sampled 300 via entrez): RS1000011585 (9:75089091 G>A), RS1000013149 (9:75088532 G>A,C,T), RS1000022544 (9:75115873 G>A), RS1000093404 (9:75122075 T>C), RS1000145780 (9:75106562 T>C), RS1000157616 (9:75110229 A>G,T), RS1000223674 (9:75113039 C>CA), RS1000333959 (9:75146328 C>G), RS1000337788 (9:75104537 C>T), RS1000621791 (9:75114471 T>G), RS1000645108 (9:75117400 C>T), RS1000673409 (9:75105744 G>A), RS1000696706 (9:75113072 G>A), RS1000722590 (9:75116009 C>G,T), RS1000764064 (9:75120969 C>A,T)

Disease associations

OMIM: gene MIM:610180 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002550_11	Allergic rhinitis	1.000000e-06
GCST002726_15	Glucose homeostasis traits	3.000000e-06
GCST005124_2	Urinary magnesium-to-creatinine ratio	4.000000e-13
GCST006138_12	Resting-state electroencephalogram vigilance	7.000000e-06
GCST006493_11	Systemic sclerosis	9.000000e-06
GCST006923_14	Loneliness	5.000000e-09
GCST006924_6	Loneliness (MTAG)	2.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement
EFO:0008449	magnesium:creatinine ratio measurement
EFO:0004357	electroencephalogram measurement
EFO:0007865	loneliness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression, affects methylation	8
Cadmium	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
nickel sulfate	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Caffeine	increases phosphorylation	1
Diethylhexyl Phthalate	increases expression	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Sulindac	increases expression	1
Tretinoin	increases expression	1
Vanadates	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Cyclosporine	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A5A5	SEES3-1V human OSTF1, clone1	Embryonic stem cell	Male
CVCL_A5A6	SEES3-1V human OSTF1, clone2	Embryonic stem cell	Male
CVCL_A5A7	SEES3-1V human OSTF1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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