SP7

Summary

SP7 (Sp7 transcription factor, HGNC:17321) is a protein-coding gene on chromosome 12q13.13, encoding Transcription factor Sp7 (Q8TDD2). Transcriptional activator essential for osteoblast differentiation.

This gene encodes a member of the Sp subfamily of Sp/XKLF transcription factors. Sp family proteins are sequence-specific DNA-binding proteins characterized by an amino-terminal trans-activation domain and three carboxy-terminal zinc finger motifs. This protein is a bone specific transcription factor and is required for osteoblast differentiation and bone formation.

Source: NCBI Gene 121340 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteogenesis imperfecta type 12 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 198 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 41
• Transcription factor: yes — 47 downstream targets (CollecTRI)
• MANE Select transcript: NM_001173467

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17321
Approved symbol	SP7
Name	Sp7 transcription factor
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	osterix, OSX
Ensembl gene	ENSG00000170374
Ensembl biotype	protein_coding
OMIM	606633
Entrez	121340

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000303846, ENST00000536324, ENST00000537210, ENST00000547755

RefSeq mRNA: 3 — MANE Select: NM_001173467 NM_001173467, NM_001300837, NM_152860

CCDS: CCDS44897, CCDS73475

Canonical transcript exons

ENST00000536324 — 3 exons

Exon	Start	End
ENSE00001152110	53326575	53329420
ENSE00002227847	53335626	53335693
ENSE00002411650	53336146	53336354

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 86.08.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 13.1698 / max 801.9943, expressed in 108 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131240	5.7726	78
131241	5.5674	69
131242	0.9130	69
131239	0.5388	59
131238	0.2340	58
131237	0.1440	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.08	gold quality
tibia	UBERON:0000979	82.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.29	silver quality
trabecular bone tissue	UBERON:0002483	60.29	silver quality
endothelial cell	CL:0000115	59.16	gold quality
prefrontal cortex	UBERON:0000451	53.83	gold quality
bone element	UBERON:0001474	49.45	silver quality
mucosa of paranasal sinus	UBERON:0005030	47.19	gold quality
frontal cortex	UBERON:0001870	46.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	46.04	gold quality
bone marrow cell	CL:0002092	45.89	gold quality
neocortex	UBERON:0001950	45.76	gold quality
spinal cord	UBERON:0002240	45.47	gold quality
amygdala	UBERON:0001876	44.60	gold quality
Brodmann (1909) area 9	UBERON:0013540	44.29	gold quality
cerebral cortex	UBERON:0000956	43.82	gold quality
cartilage tissue	UBERON:0002418	43.40	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
anterior cingulate cortex	UBERON:0009835	42.99	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	42.92	silver quality
temporal lobe	UBERON:0001871	42.63	gold quality
substantia nigra pars compacta	UBERON:0001965	42.63	gold quality
primary visual cortex	UBERON:0002436	42.62	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
calcaneal tendon	UBERON:0003701	42.46	gold quality
bone marrow	UBERON:0002371	42.44	gold quality
subthalamic nucleus	UBERON:0001906	42.07	gold quality
occipital lobe	UBERON:0002021	41.90	gold quality
right lobe of thyroid gland	UBERON:0001119	41.76	silver quality
putamen	UBERON:0001874	41.71	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.46

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

47 targets.

Target	Regulation
ADRA1D
ALPL
BGLAP	Activation
BMP2
CAMK2A
CD34	Activation
CLEC2D	Activation
COL11A2	Activation
COL1A1	Activation
COL5A1	Activation
COL5A3	Unknown
DES
DKK1
DMP1
DSPP
EPHB2
FGFR1
FMOD	Activation
GATA1	Activation
GJA1
IBSP	Activation
IFITM5	Activation
IL1A	Activation
IL6
KDM6B
KRT27
MAPK1
MARK1
ME3
MIR93

Upstream regulators (CollecTRI, top): ATF4, BMP2, BMPR1B, CCL3, CCR1, DLX5, EP300, FOXC1, HIVEP2, HOXA10, MEF2C, MSX2, MYF5, MYOD1, NFE2L1, NRF1, PAX5, PBX1, PITX2, PRRX1, RUNX2, RUNX3, SATB2, SMAD1, SMAD4, SMAD5, SP7, SPOP, STAT1, TBX3, TBXT, TMEM119, TP53

miRNA regulators (miRDB)

82 targeting SP7, 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-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3121-3P	99.82	71.96	3630
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-6764-5P	99.75	67.89	2304
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-516B-5P	99.56	66.33	1495

Literature-anchored findings (GeneRIF, showing 40)

• Telomerase accelerates osteogenesis of bone marrow stromal stem cells by upregulation of CBFA1, osterix, and osteocalcin. (PMID:12674332)
• Sp7 expression in humans is largely confined to osteoblasts and chondrocytes, both of which differentiate from the mesenchymal lineage. Of the two protein isoforms, the short isoform is most abundant. (PMID:14604442)
• The identification and initial characterization of the SP7 gene will facilitate the study of the molecular regulation of osteoblast differentiation in humans. (PMID:15474293)
• Gene expression of osterix was not detected in dental follicle cells during osteogenic differentiation. (PMID:16467978)
• results indicated that pcDNA3.1-Osx transfection promoted the osteogenic differentiation of adipose derived stem cells, while not affecting their proliferative ability (PMID:17206379)
• identified new Osterix interacting factors by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (PMID:17303075)
• osterix functions as a molecular link between mechanostressing and osteogenic differentiation (PMID:17311298)
• These results demonstrate the transcriptional regulation of Osterix expression by Runx3 during differentiation of dental pulp cells into odontoblasts during tooth development. (PMID:17352693)
• might play an important role in the mechanical stress-induced osteogenic differentiation of periodontal ligament cells (PMID:18471237)
• This is the first report demonstrating significant upregulation in expression of Runx2 and Osterix by TGF-beta3 induction of human adipose-derived stromal cells during in vitro chondrogenesis. (PMID:18482578)
• dried plum polyphenols enhance osteoblast activity and function by attenuating the effect of TNFalpha and up-regulating Runx2, Osterix and IGF-I and increasing lysyl oxidase expression, and at the same time attenuate osteoclastogenesis signaling (PMID:18495459)
• This study further confirms that the involvement of SP7 in bone physiology is not only limited to the developmental step. (PMID:18777089)
• E4BP4 has a role as osteoblast transcriptional repressor in inhibiting both Runx2 and Osterix in myeloma bone disease (PMID:18829486)
• The high Osx levels induced the commitment towards the hematopoietic-endothelial lineage-by up-regulating the expression of CD34 and Gata1. (PMID:18932205)
• The presence of NFATc1 and Osx in our material lends further support to the hypothesis that during the process of aortic valve calcification there is expression of osteoblastic phenotypes by valvular cells (PMID:19019468)
• interactions between NO66 and Osx regulate Osx-target genes in osteoblasts by modulating histone methylation states (PMID:19927124)
• Sox9, Runx2, and Osterix-were play an essential role in determining the skeletal progenitor cells’ fate in benign cartilage and bone forming tumors. (PMID:21078438)
• Evidence from a genome-wide association study (in USA; in pts of European descent) indicate that an SNP at one locus, Osterix, is associated with childhood obesity; G allele of rs2016266 is significantly over-represented in obesity but only in girls. (PMID:21212767)
• Osterix expression in fibroblasts was induced by fluoride, which could play an important role in the development of fluoride bone injuries and ossification around bone. (PMID:21351630)
• RT-PCR showed that SP7 from osteoblasts from Pfeiffer syndrome grown on PLPG acid plates were downregulated after 30 days. (PMID:21558934)
• Akt activity enhances the osteogenic function of Osterix, at least in part, through protein stabilization and that BMP-2 regulates the osteogenic function of Osterix, at least in part, through Akt. (PMID:21777568)
• Osterix, a significant transcription factor of osteoblasts, was shown to be a direct target of miR-637 (PMID:21880893)
• Osterix regulates the expression of a set of extracellular matrix proteins which are involved in BMP-induced terminal osteoblast differentiation. (PMID:21898406)
• Results suggest that Osterix is a direct transcriptional regulator with repressive effect on NELL-1 gene expression, contributing to a delicate balance of regulatory effects on NELL-1 transcription with Runx2. (PMID:21931789)
• These results suggest that Erk1/2 regulates a major transcription factor, Osterix, during osteoblast differentiation by increasing its protein stability and transcriptional activity. (PMID:22056560)
• miR-93/Sp7 function loop mediates osteoblast mineralization (PMID:22467200)
• Osterix regulates calcification and degradation of chondrogenic matrices through matrix metalloproteinase 13 (MMP13) expression in association with transcription factor Runx2 during endochondral ossification (PMID:22869368)
• Consensus Sp1 sequences, located in the proximal promoter and in the bone-enhancer, as Osterix binding regions in the Col1a1 promoter in vitro and in vivo, were identified. (PMID:23159876)
• These results suggest that Osterix is a novel target of CaMKII and the activity of Osterix can be modulated by a novel mechanism involving CaMKII during osteoblast differentiation. (PMID:23402759)
• Osx is an unstable protein, and that the ubiquitin-proteasome pathway is involved in the regulation of Osx and thereby regulates osteoblast differentiation (PMID:23457570)
• hinge domain-dependent oligomerization of NO66 is essential for inhibition of Osx-dependent gene activation. (PMID:23620590)
• MiR-31, controls Osterix expression through association to the 3’ untranslated region of this transcription factor. (PMID:23827457)
• In adamantinomatous craniopharyngioma, Bmp2 was expressed primarily in the stellate reticulum and whorl-like array cells; Runx2 and Osterix tended to be expressed in calcification-related epithelia. (PMID:24387671)
• Osterix is a novel target of protein kinase A, and protein kinase A modulates osteoblast differentiation partially through the regulation of Osterix. (PMID:24905700)
• The 2 genes RUNX1 and SP7 resulted differently expressed in cells cultured on metallic supports if compared with the expression recorded for OIC (PMID:25025858)
• results provide a molecular description of a mechanism for Osx and Runx2 transcriptional cooperation that is subject to further regulation by MAPK-activating signals during osteogenesis. (PMID:25122769)
• Runx2-Sp7 molecular complex functionally cooperate for maximal induction of cell-phenotype-restricted genes (PMID:25158187)
• Osx might function as a potential regulator for the proliferation and odontoblastic differentiation of hDPCs. (PMID:25258338)
• Pin1 regulates the osteogenic activity of Osterix. (PMID:25463757)
• c-Src signaling modulates osteoblast differentiation at least in part through phosphorylation of Osterix. (PMID:25802190)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sp7	ENSDARG00000019516
mus_musculus	Sp7	ENSMUSG00000060284
rattus_norvegicus	Sp7	ENSRNOG00000014082
drosophila_melanogaster	luna	FBGN0040765
caenorhabditis_elegans	sptf-1	WBGENE00009743

Paralogs (22): KLF6 (ENSG00000067082), KLF8 (ENSG00000102349), KLF5 (ENSG00000102554), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), KLF7 (ENSG00000118263), KLF12 (ENSG00000118922), KLF9 (ENSG00000119138), KLF2 (ENSG00000127528), KLF16 (ENSG00000129911), KLF4 (ENSG00000136826), KLF10 (ENSG00000155090), KLF15 (ENSG00000163884), SP8 (ENSG00000164651), KLF13 (ENSG00000169926), KLF17 (ENSG00000171872), KLF11 (ENSG00000172059), SP6 (ENSG00000189120), SP5 (ENSG00000204335), SP9 (ENSG00000217236), KLF14 (ENSG00000266265), KLF18 (ENSG00000283039)

Protein

Protein identifiers

Transcription factor Sp7 — Q8TDD2 (reviewed: Q8TDD2)

Alternative names: Zinc finger protein osterix

All UniProt accessions (2): Q8TDD2, F8VV67

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator essential for osteoblast differentiation. Binds to SP1 and EKLF consensus sequences and to other G/C-rich sequences.

Subunit / interactions. Interacts with RIOX1; the interaction is direct and inhibits transcription activator activity.

Subcellular location. Nucleus.

Tissue specificity. Restricted to bone-derived cell.

Post-translational modifications. Ubiquitination at leads to proteasomal degradation. SP7 is a short-live protein with an endogenous half-life of approximately 12 hours. Propionylated. Depropionylation at Lys-371 by SIRT7 activates transcription factor activity and positively regulates bone formation by osteoblasts.

Disease relevance. Osteogenesis imperfecta 12 (OI12) [MIM:613849] A form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI12 is an autosomal recessive form characterized by recurrent fractures, mild bone deformations, delayed teeth eruption, no dentinogenesis imperfecta, normal hearing, and white sclerae. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Miscellaneous. Generally expressed at much higher level than isoform 1.

Similarity. Belongs to the Sp1 C2H2-type zinc-finger protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TDD2-1	1, alpha, long	yes
Q8TDD2-2	2, beta, short

RefSeq proteins (3): NP_001166938, NP_001287766, NP_690599 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (20 total): modified residue 4, region of interest 4, zinc finger region 3, compositionally biased region 2, cross-link 2, mutagenesis site 2, chain 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDD2-F1	52.78	0.00

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 (6): 41, 45, 361, 371, 58, 230

Mutagenesis-validated functional residues (2):

Position	Phenotype
58	enhances osteogenic differentiation in c2c12 cells.
230	enhances osteogenic differentiation in c2c12 cells.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-8940973	RUNX2 regulates osteoblast differentiation
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878166	Transcriptional regulation by RUNX2
R-HSA-8941326	RUNX2 regulates bone development

MSigDB gene sets: 204 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, TAATAAT_MIR126, LFA1_Q6, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_TOOTH_MINERALIZATION, CHX10_01, GGGTGGRR_PAX4_03, GOBP_HEMATOPOIETIC_STEM_CELL_DIFFERENTIATION, GTGCCTT_MIR506, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, NF1_Q6_01, GOBP_POSITIVE_REGULATION_OF_STEM_CELL_DIFFERENTIATION, GATA1_01, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (12): osteoblast differentiation (GO:0001649), regulation of transcription by RNA polymerase II (GO:0006357), response to mechanical stimulus (GO:0009612), gene expression (GO:0010467), response to insulin (GO:0032868), cellular response to zinc ion starvation (GO:0034224), positive regulation of transcription by RNA polymerase II (GO:0045944), hematopoietic stem cell differentiation (GO:0060218), diphosphate metabolic process (GO:0071344), cellular response to parathyroid hormone stimulus (GO:0071374), cementum mineralization (GO:0071529), positive regulation of stem cell differentiation (GO:2000738)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), zinc ion binding (GO:0008270), DEAD/H-box RNA helicase binding (GO:0017151), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RUNX2 regulates bone development	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1
Transcriptional regulation by RUNX2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
stem cell differentiation	2
cellular anatomical structure	2
ossification	1
cell differentiation	1
regulation of DNA-templated transcription	1
response to external stimulus	1
response to abiotic stimulus	1
macromolecule biosynthetic process	1
response to peptide hormone	1
cellular response to starvation	1
response to zinc ion starvation	1
positive regulation of DNA-templated transcription	1
hematopoietic progenitor cell differentiation	1
phosphorus metabolic process	1
oxoacid metabolic process	1
cellular response to hormone stimulus	1
response to parathyroid hormone	1
tooth mineralization	1
positive regulation of cell differentiation	1
regulation of stem cell differentiation	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transition metal ion binding	1
enzyme binding	1
binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1980 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SP7	RUNX2	Q13950	955
SP7	NFATC1	O95644	955
SP7	RIOX1	Q9H6W3	916
SP7	BGLAP	P02818	908
SP7	IBSP	P21815	880
SP7	COL1A1	P02452	879
SP7	BMP2	P12643	875
SP7	DLX5	P56178	871
SP7	SOST	Q9BQB4	857
SP7	LRP5	O75197	838
SP7	CTNNB1	P35222	829
SP7	SPP1	P10451	822
SP7	TNFSF11	O14788	786
SP7	ALPL	P05186	781
SP7	TNFRSF11B	O00300	735

IntAct

25 interactions, top by confidence:

A	B	Type	Score
SP7	TRIM62	psi-mi:“MI:0915”(physical association)	0.560
SP7	FAM124B	psi-mi:“MI:0915”(physical association)	0.560
GAS8	SP7	psi-mi:“MI:0915”(physical association)	0.560
QARS1	SP7	psi-mi:“MI:0915”(physical association)	0.560
NFIA	SP7	psi-mi:“MI:0915”(physical association)	0.470
NFIB	SP7	psi-mi:“MI:0915”(physical association)	0.470
NFIC	SP7	psi-mi:“MI:0915”(physical association)	0.470
SP7	GSK3B	psi-mi:“MI:0915”(physical association)	0.460
SP7	GSK3B	psi-mi:“MI:0403”(colocalization)	0.460
SP7	PPP6C	psi-mi:“MI:0914”(association)	0.350
SP7	EPHA2	psi-mi:“MI:0914”(association)	0.350
SP7	IGF2BP3	psi-mi:“MI:2364”(proximity)	0.270
GAS8	SP7	psi-mi:“MI:0915”(physical association)	0.000
QARS1	SP7	psi-mi:“MI:0915”(physical association)	0.000
TRIM62	SP7	psi-mi:“MI:0915”(physical association)	0.000
FAM124B	SP7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (305): SP7 (Affinity Capture-Western), STUB1 (Affinity Capture-Western), CBL (Affinity Capture-Western), CBLB (Affinity Capture-Western), SP7 (Affinity Capture-Western), SP7 (Affinity Capture-Western), CBLB (Reconstituted Complex), CBL (Reconstituted Complex), SP7 (Affinity Capture-MS), SP7 (Two-hybrid), SP7 (Two-hybrid), SP7 (Two-hybrid), QARS (Two-hybrid), SP7 (Affinity Capture-Western), SP7 (Affinity Capture-Western)

ESM2 similar proteins: A2A5K6, A5A763, A7X8B9, A7X8C2, A7X8C4, A7X8C9, A7X8D4, A7XW16, D4A8X0, E9PYH6, E9PZZ1, F1QQA8, G3V893, O08550, O15047, O15156, O43474, O55170, O95503, P16443, P19419, P42580, P50548, P56693, P70459, Q04888, Q14549, Q3B8N7, Q5F293, Q60793, Q62255, Q8CGW4, Q8TDD2, Q8VI67, Q8WUU4, Q91X45, Q924A2, Q96RK0, Q99PV8, Q9BZE0

Diamond homologs: A5ABV9, O08876, O14901, O70494, O89090, O89091, P08047, P0CG40, P41696, Q01714, Q02446, Q02447, Q0VA40, Q13351, Q22678, Q3SY56, Q5XGT8, Q62445, Q64HY3, Q64HY5, Q6BEB4, Q6NW96, Q6P0J3, Q8BMJ8, Q8IXZ3, Q8K1S5, Q8TDD2, Q8VI67, Q90WR8, Q9ESX2, Q9JHX2, Q9TZ64, A1C6L9, A1DH89, A2QCJ9, B0XSK6, B8NGC8, G4N3L5, K9GKQ6, O14335

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
AKT	up-regulates	SP7	phosphorylation
AKT1	up-regulates	SP7	phosphorylation
SP7	“up-regulates quantity by expression”	IFITM5	“transcriptional regulation”
SP7	“up-regulates quantity by expression”	BGLAP	“transcriptional regulation”
RUNX2	up-regulates	SP7	“transcriptional regulation”
SP7	up-regulates	Osteoblast_differentiation
MAPK14	“up-regulates activity”	SP7	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	112
Likely benign	66
Benign	10

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
31854	NM_001173467.3(SP7):c.1052del (p.Glu351fs)	Pathogenic
2503440	NM_001173467.3(SP7):c.359_362del (p.Asp120fs)	Likely pathogenic
3572974	NM_001173467.3(SP7):c.810C>A (p.Cys270Ter)	Likely pathogenic

SpliceAI

352 predictions. Top by Δscore:

Variant	Effect	Δscore
12:53336143:TA:T	donor_loss	0.9900
12:53336144:ACCTG:A	donor_loss	0.9900
12:53336145:C:CT	donor_loss	0.9900
12:53336180:T:A	donor_gain	0.9800
12:53329288:TGCC:T	donor_gain	0.9300
12:53336153:A:AT	donor_gain	0.9100
12:53335700:C:CT	acceptor_gain	0.8900
12:53335706:G:GC	acceptor_gain	0.8800
12:53329313:G:A	donor_gain	0.8700
12:53335701:G:T	acceptor_gain	0.8600
12:53329180:AG:A	donor_gain	0.8500
12:53335706:G:C	acceptor_gain	0.8500
12:53329301:CGG:C	donor_gain	0.8400
12:53335715:G:C	acceptor_gain	0.8300
12:53335715:G:GC	acceptor_gain	0.8200
12:53335694:C:CC	acceptor_gain	0.8100
12:53335691:GAG:G	acceptor_gain	0.8000
12:53336026:T:TA	donor_gain	0.7900
12:53336144:A:AC	donor_gain	0.7900
12:53336145:C:CC	donor_gain	0.7900
12:53329258:C:A	donor_gain	0.7800
12:53328632:G:GT	acceptor_gain	0.7700
12:53335621:GTTA:G	donor_loss	0.7700
12:53335622:TTACC:T	donor_loss	0.7700
12:53335623:TACCT:T	donor_loss	0.7700
12:53335624:A:G	donor_loss	0.7700
12:53335625:C:CA	donor_loss	0.7700
12:53335619:CAGTT:C	donor_loss	0.7600
12:53335620:AGTTA:A	donor_loss	0.7600
12:53336145:CCTGG:C	donor_gain	0.7600

AlphaMissense

2762 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:53328326:G:C	H372Q	1.000
12:53328326:G:T	H372Q	1.000
12:53328328:G:C	H372D	1.000
12:53328328:G:T	H372N	1.000
12:53328353:A:C	F363L	1.000
12:53328353:A:T	F363L	1.000
12:53328354:A:C	F363C	1.000
12:53328354:A:G	F363S	1.000
12:53328355:A:G	F363L	1.000
12:53328365:G:C	C359W	1.000
12:53328367:A:G	C359R	1.000
12:53328374:G:C	C356W	1.000
12:53328376:A:G	C356R	1.000
12:53328380:G:C	F354L	1.000
12:53328380:G:T	F354L	1.000
12:53328382:A:G	F354L	1.000
12:53328398:G:C	H348Q	1.000
12:53328398:G:T	H348Q	1.000
12:53328400:G:C	H348D	1.000
12:53328410:A:C	H344Q	1.000
12:53328410:A:T	H344Q	1.000
12:53328412:G:C	H344D	1.000
12:53328412:G:T	H344N	1.000
12:53328437:G:C	F335L	1.000
12:53328437:G:T	F335L	1.000
12:53328438:A:C	F335C	1.000
12:53328438:A:G	F335S	1.000
12:53328439:A:G	F335L	1.000
12:53328450:C:T	C331Y	1.000
12:53328464:G:C	C326W	1.000

dbSNP variants (sampled 300 via entrez): RS1000189751 (12:53329292 C>T), RS1000254718 (12:53335853 G>A,C,T), RS1000328732 (12:53331391 A>AACC), RS1000383135 (12:53341726 C>T), RS1000383863 (12:53343987 G>T), RS1000415733 (12:53341376 G>A), RS1000702013 (12:53342074 A>C), RS1001197478 (12:53343046 A>G), RS1001298289 (12:53336899 C>A), RS1001412126 (12:53331259 CA>C), RS1001666138 (12:53336570 C>T), RS1001860976 (12:53330616 C>T), RS1001962773 (12:53336670 G>T), RS1002089994 (12:53341287 C>G,T), RS1002092391 (12:53342759 G>A)

Disease associations

OMIM: gene MIM:606633 | disease phenotypes: MIM:613849, MIM:166200

GenCC curated gene-disease

Disease	Classification	Inheritance
osteogenesis imperfecta type 12	Strong	Autosomal recessive
osteogenesis imperfecta type 4	Supportive	Autosomal dominant

Mondo (3): osteogenesis imperfecta type 12 (MONDO:0013460), osteogenesis imperfecta (MONDO:0019019), osteogenesis imperfecta type 4 (MONDO:0008148)

Orphanet (1): Osteogenesis imperfecta (Orphanet:666)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000244	Brachyturricephaly
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000324	Facial asymmetry
HP:0000336	Prominent supraorbital ridges
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000402	Stenosis of the external auditory canal
HP:0000405	Conductive hearing impairment
HP:0000431	Wide nasal bridge
HP:0000591	Abnormal sclera morphology
HP:0000592	Blue sclerae
HP:0000648	Optic atrophy
HP:0000684	Delayed eruption of teeth
HP:0000703	Dentinogenesis imperfecta
HP:0000768	Pectus carinatum
HP:0000772	Abnormal rib morphology
HP:0000939	Osteoporosis
HP:0001187	Hyperextensibility of the finger joints
HP:0001249	Intellectual disability
HP:0001270	Motor delay
HP:0002007	Frontal bossing
HP:0002645	Wormian bones
HP:0002650	Scoliosis
HP:0002757	Recurrent fractures
HP:0002979	Bowing of the legs
HP:0003593	Infantile onset

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000295_5	Bone mineral density (spine)	1.000000e-07
GCST000494_1	Bone mineral density (spine)	1.000000e-08
GCST001482_12	Lumbar spine bone mineral density	3.000000e-20
GCST005993_56	Mean corpuscular hemoglobin	3.000000e-15
GCST006979_1058	Heel bone mineral density	7.000000e-18
GCST008839_211	Height	1.000000e-29
GCST009672_1	Hypospadias (moderate to severe)	4.000000e-09
GCST010241_90	Apolipoprotein A1 levels	5.000000e-13
GCST010242_136	HDL cholesterol levels	2.000000e-12
GCST90002390_61	Mean corpuscular hemoglobin	3.000000e-09
GCST90002392_383	Mean corpuscular volume	8.000000e-11
GCST90011900_77	Serum alkaline phosphatase levels	2.000000e-18
GCST90013406_16	Liver enzyme levels (alkaline phosphatase)	1.000000e-41
GCST90020025_25	Waist-to-hip ratio adjusted for BMI	6.000000e-09
GCST90020027_1704	Waist-hip index	9.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0009270	heel bone mineral density
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
beta-glycerophosphoric acid	affects cotreatment, increases expression, decreases reaction	4
Dexamethasone	affects cotreatment, increases expression, decreases reaction, decreases expression	4
bisphenol A	decreases reaction, increases expression, decreases expression	2
ascorbate-2-phosphate	decreases reaction, increases expression, affects cotreatment	2
Resveratrol	increases expression, decreases reaction	2
Fulvestrant	decreases reaction, increases expression	2
Ascorbic Acid	affects cotreatment, increases expression, decreases reaction, decreases expression	2
Cadmium	decreases expression, decreases reaction, increases abundance	2
Tetrachlorodibenzodioxin	affects expression	2
Cadmium Chloride	decreases expression, decreases reaction, increases abundance	2
protosappanin B	increases expression	1
naringin	decreases expression, decreases reaction	1
aucubin	increases expression	1
titanium dioxide	increases expression	1
tributyltin	decreases reaction, increases expression, affects cotreatment	1
pyrrolidine dithiocarbamic acid	increases expression, affects cotreatment, decreases reaction	1
isonicotinamide	increases expression	1
zirconium oxide	increases expression	1
alpha-glycerophosphoric acid	affects cotreatment, decreases expression	1
2,4-di-tert-butylphenol	decreases expression, affects cotreatment	1
cordycepin	affects cotreatment, decreases reaction, increases expression	1
notoginsenoside R1	decreases reaction, increases expression	1
anacardic acid	decreases reaction, increases expression	1
protosappanin A	increases expression	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases expression, decreases reaction, increases expression	1
ginkgolic acid	decreases reaction, increases expression	1
SAG compound	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
SR 3335	decreases expression, decreases reaction	1
Rosiglitazone	decreases reaction, increases expression, affects cotreatment	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HC95	HEK293 eGFP-SP7	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00131469	PHASE4	COMPLETED	Study of Teriparatide (FORTEO) to Treat Adults With Osteogenesis Imperfecta
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT01713231	PHASE4	COMPLETED	Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
NCT02303873	PHASE4	COMPLETED	Efficacy and Safety of Alendronate in Chinese Children or Adolescents With Osteogenesis Imperfecta
NCT03735537	PHASE4	COMPLETED	Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid
NCT04152551	PHASE4	RECRUITING	Effects of Bisphosphonates on OI-Related Hearing Loss
NCT00001305	PHASE3	COMPLETED	Growth Hormone Therapy in Osteogenesis Imperfecta
NCT00005901	PHASE3	COMPLETED	Pamidronate to Treat Osteogenesis Imperfecta in Children
NCT00106028	PHASE3	COMPLETED	Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
NCT00982124	PHASE3	COMPLETED	An Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta
NCT02352753	PHASE3	TERMINATED	Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
NCT03638128	PHASE3	TERMINATED	Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta
NCT05768854	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
NCT05972551	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
NCT06636071	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta
NCT07366086	PHASE3	RECRUITING	Pediatric Safety Follow-up Study of Prior Treatment With Romosozumab for Osteogenesis Imperfecta
NCT03118570	PHASE2	COMPLETED	A Study in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With BPS804
NCT00063479	PHASE2	COMPLETED	Bisphosphonate Treatment of Osteogenesis Imperfecta
NCT00131118	PHASE2	COMPLETED	Zoledronic Acid in Children (1 -17 Years) With Severe Osteogenesis Imperfecta
NCT01417091	PHASE2	COMPLETED	Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
NCT01679080	PHASE2	TERMINATED	The Effect of Treatment With Teriparatide and Zoledronic Acid in Patients With Osteogenesis Imperfecta
NCT01799798	PHASE2	COMPLETED	Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
NCT03208582	PHASE2	COMPLETED	Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
NCT03216486	PHASE2	WITHDRAWN	An Exploratory Study of BPS804 Treatment in Adult Patients With Type I, III or IV Osteogenesis Imperfecta
NCT05312697	PHASE2	TERMINATED	Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta
NCT07062588	PHASE2	RECRUITING	Osteogenesis Imperfecta Trial of AGA2115 for ADUlts With COL1A1 and/or COL1A2 GeNetic Variations (IDUN)
NCT07557446	PHASE2	NOT_YET_RECRUITING	A Dose REgimen-Finding Study of AGA2115 in Chinese Patients With Osteogenesis ImpeRfecta (EIR)
NCT00705120	PHASE1	COMPLETED	Treatment of Severe Osteogenesis Imperfecta by Allogeneic Bone Marrow Transplantation
NCT02172885	PHASE1	COMPLETED	Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta
NCT03064074	PHASE1	COMPLETED	Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta
NCT04545554	PHASE1	COMPLETED	Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
NCT05231668	PHASE1	TERMINATED	Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)
NCT06086613	PHASE1	COMPLETED	A First-in-Human Study Evaluating AGA2115 in Adult Healthy Volunteers
NCT05125809	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Placebo for Osteogenesis Imperfecta
NCT03706482	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Boost Brittle Bones Before Birth
NCT04623606	PHASE1/PHASE2	UNKNOWN	Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones
NCT05559801	PHASE1/PHASE2	NOT_YET_RECRUITING	Mesenchymal Cell Therapy in Osteogenesis Imperfecta (OI)
NCT00001594	Not specified	COMPLETED	Evaluation and Intervention for the Effects of Osteogenesis Imperfecta
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease
NCT00187018	Not specified	COMPLETED	Marrow Mesenchymal Cell Therapy for Osteogenesis Imperfecta: A Pilot Study