OSTN

Summary

OSTN (osteocrin, HGNC:29961) is a protein-coding gene on chromosome 3q28, encoding Osteocrin (P61366). Hormone that acts as a regulator of dendritic growth in the developing cerebral cortex in response to sensory experience.

Predicted to enable signaling receptor binding activity. Involved in negative regulation of dendrite extension. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 344901 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_198184

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29961
Approved symbol	OSTN
Name	osteocrin
Location	3q28
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188729
Ensembl biotype	protein_coding
OMIM	610280
Entrez	344901

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000445281, ENST00000682035

RefSeq mRNA: 1 — MANE Select: NM_198184 NM_198184

CCDS: CCDS3299

Canonical transcript exons

ENST00000682035 — 5 exons

Exon	Start	End
ENSE00001364346	191218747	191218961
ENSE00001373881	191250037	191250133
ENSE00001714458	191199241	191199307
ENSE00003756838	191212533	191212634
ENSE00003916622	191262866	191265615

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 74.76.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5817 / max 533.2549, expressed in 52 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40575	0.5817	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.76	gold quality
cortical plate	UBERON:0005343	72.58	gold quality
prefrontal cortex	UBERON:0000451	71.03	gold quality
superior frontal gyrus	UBERON:0002661	69.69	gold quality
primary visual cortex	UBERON:0002436	65.25	gold quality
anterior cingulate cortex	UBERON:0009835	65.02	gold quality
frontal cortex	UBERON:0001870	64.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	62.18	gold quality
cerebral cortex	UBERON:0000956	61.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	60.93	gold quality
right uterine tube	UBERON:0001302	57.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	57.37	gold quality
corpus callosum	UBERON:0002336	56.53	gold quality
right frontal lobe	UBERON:0002810	53.69	gold quality
fallopian tube	UBERON:0003889	53.43	gold quality
gastrocnemius	UBERON:0001388	52.47	gold quality
muscle of leg	UBERON:0001383	51.49	gold quality
sural nerve	UBERON:0015488	51.13	gold quality
hypothalamus	UBERON:0001898	50.61	gold quality
temporal lobe	UBERON:0001871	50.05	gold quality
amygdala	UBERON:0001876	50.04	gold quality
skeletal muscle tissue	UBERON:0001134	49.96	silver quality
gall bladder	UBERON:0002110	49.66	gold quality
mucosa of transverse colon	UBERON:0004991	49.32	gold quality
urinary bladder	UBERON:0001255	49.31	gold quality
brain	UBERON:0000955	48.86	gold quality
left uterine tube	UBERON:0001303	48.67	gold quality
substantia nigra	UBERON:0002038	48.55	gold quality
calcaneal tendon	UBERON:0003701	48.55	gold quality
apex of heart	UBERON:0002098	48.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1

Literature-anchored findings (GeneRIF, showing 11)

• osteocrin represents a novel, unique vitamin D-regulated bone-specific protein that appears to act as a soluble osteoblast regulator (PMID:14523025)
• Foxo1 downregulates musclin mRNA expression both in vitro and in vivo, which should explain insulin-mediated upregulation of this gene in muscle cells. (PMID:17950246)
• Ostn is a naturally occurring ligand of the NPR-C clearance receptor and may act to locally modulate the actions of the natriuretic system in bone by blocking the clearance action of NPR-C, thus locally elevating levels of C-type natriuretic peptide. (PMID:17951249)
• findings suggest that, in response to sensory input, OSTN regulates features of neuronal structure and function that are unique to primates (PMID:27830782)
• The circulating concentration of musclin was significantly increased in type 2 diabetes mellitus patients. Results suggest that musclin has a strong relationship with insulin resistance in type 2 diabetes mellitus. (PMID:28185530)
• This study demonstrated that a female-specific role OSTN in tau pathology (PMID:29967939)
• Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin. (PMID:34725346)
• Skeletal muscle derived Musclin protects the heart during pathological overload. (PMID:35013221)
• Nestin and osteocrin mRNA increases in human semitendinosus myotendinous junction 7 days after a single bout of eccentric exercise. (PMID:35428952)
• Musclin attenuates lipid deposition in hepatocytes through SIRT7/autophagy-mediated suppression of ER stress. (PMID:37023616)
• The correlation of serum musclin with diabetic nephropathy. (PMID:37137178)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ostn	ENSDARG00000054055
mus_musculus	Ostn	ENSMUSG00000052276
rattus_norvegicus	Ostn	ENSRNOG00000030462

Protein

Protein identifiers

Osteocrin — P61366 (reviewed: P61366)

Alternative names: Musclin

All UniProt accessions (2): C9JER6, P61366

UniProt curated annotations — full annotation on UniProt →

Function. Hormone that acts as a regulator of dendritic growth in the developing cerebral cortex in response to sensory experience. Induced in the brain following membrane depolarization and inhibits dendritic branching in neurons of the developing cortex. Probably acts by binding to natriuretic peptide receptor NPR3/NPR-C, thereby preventing binding between NPR3/NPR-C and natriuretic peptides, leading to increase cGMP production.

Subunit / interactions. Interacts with NPR3.

Subcellular location. Secreted.

Tissue specificity. Enriched in neocortical regions of the developing cerebral cortex. Not expressed in other compartments of the neocortical wall or in brain regions such as the hippocampus, striatum, mediodorsal nucleus of the thalamus and cerebellum. Also expressed in bone. In developing neonatal rib bone, present at high level in osteoblasts on bone-forming surfaces, in newly incorporated osteocytes and in some late hypertrophic chondrocytes (at protein level). In adult bone, localizes specifically to osteoblasts and young osteocytes at bone-forming sites (at protein level).

Induction. Expression is induced in the developing cerebral cortex in response to neuronal activity in neurons: expression is driven by the presence of a enhancer sequence only present in primates that binds the MEF2 transcription factors.

Similarity. Belongs to the Osteocrin family.

RefSeq proteins (1): NP_937827* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021088	Osteocrin	Family

Pfam: PF11037

UniProt features (4 total): signal peptide 1, chain 1, peptide 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61366-F1	66.01	0.11

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 (1): 132

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_BONE_GROWTH, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_BONE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (11): endochondral bone growth (GO:0003416), cell surface receptor signaling pathway (GO:0007166), hormone-mediated signaling pathway (GO:0009755), cell differentiation (GO:0030154), negative regulation of osteoblast differentiation (GO:0045668), negative regulation of D-glucose import across plasma membrane (GO:0046325), bone growth (GO:0098868), negative regulation of dendrite extension (GO:1903860), cGMP biosynthetic process (GO:0006182), regulation of blood pressure (GO:0008217), regulation of osteoblast proliferation (GO:0033688)

GO Molecular Function (2): signaling receptor binding (GO:0005102), hormone activity (GO:0005179)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
bone growth	1
cellular response to hormone stimulus	1
cellular developmental process	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
negative regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
organ growth	1
bone development	1
negative regulation of cell growth	1
negative regulation of developmental growth	1
dendrite extension	1
regulation of dendrite extension	1
purine ribonucleotide biosynthetic process	1
cyclic nucleotide biosynthetic process	1
cGMP metabolic process	1
blood circulation	1
regulation of biological quality	1
osteoblast proliferation	1
regulation of cell population proliferation	1
protein binding	1
receptor ligand activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

550 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSTN	NPR3	P17342	727
OSTN	NPPC	P23582	712
OSTN	GMNC	A6NCL1	683
OSTN	BGLAP	P02818	657
OSTN	FNDC5	Q8NAU1	608
OSTN	NPPA	P01160	606
OSTN	NPR1	P16066	588
OSTN	NPR2	P20594	507
OSTN	PPARGC1A	Q9UBK2	498
OSTN	INS	P01308	487
OSTN	MSTN	O14793	476
OSTN	UTS2B	Q765I0	461
OSTN	QRFP	P83859	453
OSTN	BTBD8	Q5XKL5	449
OSTN	FSTL1	Q12841	447

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PCNP	PAPSS2	psi-mi:“MI:0914”(association)	0.350
OSTN	PEA15	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): OSTN (Synthetic Lethality), FAM107B (Affinity Capture-MS), LRRC23 (Affinity Capture-MS), OSTN (Affinity Capture-MS), PEA15 (Affinity Capture-MS), PTPRU (Reconstituted Complex)

ESM2 similar proteins: A0A023VZR2, A0A023W0B6, A0A023W0C3, A0A023W0V9, A0A023W0W9, A0A023W157, A0A023W163, A0A023W168, A0A3G1VU73, A0A3G1VU77, A0A3G1VU78, A0A3G1VU81, A0A3G1VU84, B9TQX1, B9TQX3, B9WZ56, E2AIS8, G7NYP9, O02036, O42143, O42144, P01362, P05305, P06308, P0CJ15, P0CJ16, P0CV00, P0DPY2, P0DQF5, P0DQG1, P10552, P17685, P17686, P21259, P41870, P41876, P49794, P61364, P61365, P61366

Diamond homologs: G7NYP9, P61364, P61365, P61366

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

355 predictions. Top by Δscore:

Variant	Effect	Δscore
3:191218741:TTATA:T	acceptor_loss	1.0000
3:191218744:TA:T	acceptor_loss	1.0000
3:191218746:G:A	acceptor_loss	1.0000
3:191218959:GAG:G	donor_gain	1.0000
3:191218960:AGGT:A	donor_loss	1.0000
3:191218962:GTA:G	donor_loss	1.0000
3:191218963:T:A	donor_loss	1.0000
3:191212630:CAGAG:C	donor_loss	0.9900
3:191212631:AGAGG:A	donor_loss	0.9900
3:191212632:GAG:G	donor_gain	0.9900
3:191212633:AGG:A	donor_loss	0.9900
3:191212634:GGTA:G	donor_loss	0.9900
3:191212636:T:A	donor_loss	0.9900
3:191218745:A:AG	acceptor_gain	0.9900
3:191218746:G:GG	acceptor_gain	0.9900
3:191218746:GGC:G	acceptor_gain	0.9900
3:191218746:GGCC:G	acceptor_gain	0.9900
3:191218746:GGCCT:G	acceptor_gain	0.9900
3:191218962:G:GG	donor_gain	0.9900
3:191230980:G:GT	donor_gain	0.9900
3:191212601:A:T	donor_gain	0.9800
3:191218745:AG:A	acceptor_gain	0.9800
3:191218746:GG:G	acceptor_gain	0.9800
3:191218957:CAGAG:C	donor_gain	0.9800
3:191230984:T:G	donor_gain	0.9800
3:191212600:G:GT	donor_gain	0.9700
3:191218737:T:TA	acceptor_gain	0.9700
3:191235408:A:AG	donor_gain	0.9700
3:191235409:G:GG	donor_gain	0.9700
3:191235459:G:GT	donor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000028041 (3:191199863 T>G), RS1000031781 (3:191218191 C>A,T), RS1000159717 (3:191205165 G>A), RS1000161186 (3:191235664 C>A), RS1000211684 (3:191248911 C>T), RS1000262281 (3:191198961 C>T), RS1000300609 (3:191217673 T>C), RS1000311320 (3:191199195 G>A), RS1000336438 (3:191198992 G>A), RS1000356427 (3:191212156 A>G), RS1000384542 (3:191242569 A>G,T), RS1000456765 (3:191254622 A>G), RS1000457970 (3:191265358 A>G), RS1000473532 (3:191235179 A>G), RS1000525804 (3:191235473 T>A,G)

Disease associations

OMIM: gene MIM:610280 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002874_39	Psoriasis	2.000000e-07
GCST003488_14	Response to fenofibrate (triglyceride levels)	8.000000e-07
GCST004070_11	Cerebrospinal P-tau181p levels	6.000000e-10
GCST004071_3	Cerebrospinal T-tau levels	3.000000e-11
GCST007147_1	Lateral ventricular volume in normal aging	1.000000e-16
GCST008839_334	Height	6.000000e-17
GCST008839_526	Height	9.000000e-12
GCST011616_42	Cortical volume	2.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007681	triglyceride change measurement
EFO:0004763	p-tau measurement
EFO:0004760	t-tau measurement
EFO:0008487	lateral ventricle volume measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
decabromobiphenyl ether	affects expression	1
ferrous chloride	increases expression	1
Troglitazone	increases expression	1
Cadmium	decreases expression	1
Dimethyl Sulfoxide	affects expression	1
Phthalic Acids	decreases methylation	1
Thapsigargin	increases expression	1

Clinical trials (associated diseases)

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