BMP6

Summary

BMP6 (bone morphogenetic protein 6, HGNC:1073) is a protein-coding gene on chromosome 6p24.3, encoding Bone morphogenetic protein 6 (P22004). Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes including cartilage and bone formation.

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates a wide range of biological processes including iron homeostasis, fat and bone development, and ovulation. Differential expression of this gene may be associated with progression of breast and prostate cancer. Mutations in this gene may be associated with iron overload in human patients.

Source: NCBI Gene 654 — RefSeq curated summary.

At a glance

• Gene–disease (curated): iron overload, susceptibility to (Moderate, GenCC)
• GWAS associations: 37 (top 3% of genes corpus-wide)
• Clinical variants (ClinVar): 139 total — 1 pathogenic, 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈12% of expected missense variation)
• GTEx eGene: eQTL in 12 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 50
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 0.94 (loss-of-function intolerant), LOEUF 0.52 (moderately constrained)
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_001718
• Notable: 139 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1073
Approved symbol	BMP6
Name	bone morphogenetic protein 6
Location	6p24.3
Locus type	gene with protein product
Status	Approved
Aliases	VGR1
Ensembl gene	ENSG00000153162
Ensembl biotype	protein_coding
OMIM	112266
Entrez	654

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 nonsense_mediated_decay

MANE Select: ENST00000283147

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000283147, ENST00000946083, ENST00001041917, ENST00001041918, ENST00001124916, ENST00001141307

RefSeq mRNA: 1 — MANE Select: NM_001718 NM_001718

CCDS: CCDS4503

Canonical transcript exons

ENST00000283147 — 7 exons

Exon	Start	End
ENSE00001009161	7726099	7727619
ENSE00001083364	7845140	7845332
ENSE00001083374	7862301	7862498
ENSE00001154849	7879991	7880101
ENSE00001154858	7879074	7879150
ENSE00001154874	7861451	7861599
ENSE00001258022	7880194	7881728

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 97.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.1348 / max 138.6221, expressed in 957 samples.

Highest expression (Bgee): secondary oocyte, cartilage tissue, oocyte, lung, monocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BMP6 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	5.2e-26	-0.43	6:7804144:T:C
Cells Cultured fibroblasts	eqtl	3.4e-05	+0.16	6:7646054:C:T
Whole Blood	eqtl	2.4e-04	-0.28	6:7692045:A:G
Esophagus Muscularis	sqtl	2.4e-03	+1.12	6:7861325:TG:T
Cells EBV-transformed lymphocytes	eqtl	4.2e-03	-0.34	6:7870360:G:T
Brain Frontal Cortex BA9	eqtl	1.3e-02	-0.24	6:6859629:A:AATTG
Brain Nucleus accumbens basal ganglia	sqtl	2.0e-02	+0.82	6:6877949:G:C
Liver	eqtl	2.5e-02	-0.35	6:7991679:G:T
Skin Sun Exposed Lower leg	eqtl	2.8e-02	+0.11	6:6872880:G:A
Pancreas	eqtl	3.0e-02	-0.93	6:6835299:G:C
Spleen	eqtl	3.6e-02	-0.24	6:8189893:T:G
Pituitary	eqtl	3.7e-02	+0.14	6:7531763:G:A
Colon Sigmoid	eqtl	4.6e-02	-0.21	6:7820403:G:A
Esophagus Mucosa	eqtl	4.7e-02	-0.54	6:7033393:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
65710	5.1348	957

Top tissues by expression

showing 100 of 281 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.17	gold quality
cartilage tissue	UBERON:0002418	96.49	gold quality
oocyte	CL:0000023	96.05	gold quality
right lung	UBERON:0002167	83.81	gold quality
monocyte	CL:0000576	82.43	gold quality
mononuclear cell	CL:0000842	82.10	gold quality
periodontal ligament	UBERON:0008266	81.42	gold quality
leukocyte	CL:0000738	81.24	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.10	gold quality
omental fat pad	UBERON:0010414	80.10	gold quality
peritoneum	UBERON:0002358	80.05	gold quality
pigmented layer of retina	UBERON:0001782	79.72	gold quality
adipose tissue of abdominal region	UBERON:0007808	79.61	gold quality
tibia	UBERON:0000979	78.43	gold quality
adipose tissue	UBERON:0001013	78.22	gold quality
connective tissue	UBERON:0002384	77.72	gold quality
right coronary artery	UBERON:0001625	76.20	gold quality
decidua	UBERON:0002450	75.38	silver quality
adrenal tissue	UBERON:0018303	75.38	gold quality
upper lobe of left lung	UBERON:0008952	75.24	gold quality
tibial artery	UBERON:0007610	75.06	gold quality
popliteal artery	UBERON:0002250	75.04	gold quality
upper lobe of lung	UBERON:0008948	74.45	gold quality
left ovary	UBERON:0002119	72.70	gold quality
metanephros cortex	UBERON:0010533	72.40	gold quality
placenta	UBERON:0001987	72.31	gold quality
right ovary	UBERON:0002118	72.03	gold quality
bone marrow cell	CL:0002092	71.88	gold quality
aorta	UBERON:0000947	71.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.30	gold quality
calcaneal tendon	UBERON:0003701	70.77	gold quality
right atrium auricular region	UBERON:0006631	70.52	gold quality
choroid plexus epithelium	UBERON:0003911	70.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	70.51	gold quality
lung	UBERON:0002048	70.45	gold quality
smooth muscle tissue	UBERON:0001135	70.13	gold quality
tibial nerve	UBERON:0001323	69.85	gold quality
tendon	UBERON:0000043	69.79	gold quality
muscle of leg	UBERON:0001383	69.49	gold quality
gastrocnemius	UBERON:0001388	69.27	gold quality
rectum	UBERON:0001052	69.21	gold quality
left coronary artery	UBERON:0001626	69.05	gold quality
cardiac atrium	UBERON:0002081	68.90	gold quality
colonic epithelium	UBERON:0000397	68.66	silver quality
tendon of biceps brachii	UBERON:0008188	68.65	silver quality
ovary	UBERON:0000992	68.24	gold quality
coronary artery	UBERON:0001621	68.05	gold quality
adult mammalian kidney	UBERON:0000082	67.95	gold quality
ascending aorta	UBERON:0001496	67.95	gold quality
left adrenal gland	UBERON:0001234	67.93	gold quality
caudate nucleus	UBERON:0001873	67.90	gold quality
transverse colon	UBERON:0001157	67.78	gold quality
left adrenal gland cortex	UBERON:0035825	67.74	gold quality
skin of leg	UBERON:0001511	67.56	gold quality
apex of heart	UBERON:0002098	67.55	gold quality
mucosa of transverse colon	UBERON:0004991	67.40	gold quality
nucleus accumbens	UBERON:0001882	67.39	gold quality
thoracic aorta	UBERON:0001515	67.38	gold quality
putamen	UBERON:0001874	67.38	gold quality
gall bladder	UBERON:0002110	67.36	gold quality
left uterine tube	UBERON:0001303	67.16	gold quality
adrenal gland	UBERON:0002369	67.06	gold quality
lower esophagus muscularis layer	UBERON:0035833	66.97	gold quality
pituitary gland	UBERON:0000007	66.96	gold quality
body of uterus	UBERON:0009853	66.96	gold quality
right adrenal gland	UBERON:0001233	66.91	gold quality
ventricular zone	UBERON:0003053	66.87	gold quality
lower esophagus	UBERON:0013473	66.86	gold quality
renal medulla	UBERON:0000362	66.85	gold quality
endocervix	UBERON:0000458	66.79	gold quality
heart	UBERON:0000948	66.55	gold quality
body of stomach	UBERON:0001161	66.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	66.26	gold quality
skin of hip	UBERON:0001554	66.24	silver quality
right adrenal gland cortex	UBERON:0035827	66.22	gold quality
heart left ventricle	UBERON:0002084	66.08	gold quality
granulocyte	CL:0000094	65.97	gold quality
spleen	UBERON:0002106	65.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	65.84	gold quality
adenohypophysis	UBERON:0002196	65.82	gold quality
adrenal cortex	UBERON:0001235	65.79	gold quality
muscle layer of sigmoid colon	UBERON:0035805	65.69	gold quality
blood	UBERON:0000178	65.64	gold quality
cardiac ventricle	UBERON:0002082	65.53	gold quality
muscle organ	UBERON:0001630	65.41	gold quality
skeletal muscle organ	UBERON:0014892	65.41	gold quality
amygdala	UBERON:0001876	65.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	64.88	gold quality
colon	UBERON:0001155	64.85	gold quality
skin of abdomen	UBERON:0001416	64.81	gold quality
zone of skin	UBERON:0000014	64.72	gold quality
stomach	UBERON:0000945	64.71	gold quality
minor salivary gland	UBERON:0001830	64.71	gold quality
vermiform appendix	UBERON:0001154	64.55	gold quality
prefrontal cortex	UBERON:0000451	64.32	gold quality
urinary bladder	UBERON:0001255	64.31	gold quality
descending thoracic aorta	UBERON:0002345	64.25	gold quality
large intestine	UBERON:0000059	64.24	gold quality
ileal mucosa	UBERON:0000331	64.22	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	169.49
E-MTAB-9543	yes	29.99
E-ANND-3	yes	6.65

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Ovary	tissue	19.2	not detected
Placenta	tissue	17.0	not detected
Superior colliculi	tissue	13.3
Choroid plexus	tissue	12.9
Spinal cord	tissue	8.1
Basal ganglia	tissue	7.7	not detected
Nucleus accumbens	tissue	7.4
Adipose tissue	tissue	7.3	not detected
Substantia nigra	tissue	6.5
Kidney	tissue	6.2	not detected
Putamen	tissue	6.0
Lung	tissue	5.3	not detected
Stomach 1	tissue	4.4	not detected
Heart muscle	tissue	4.3	not detected
Spleen	tissue	4.3	not detected
Hippocampus	tissue	4.2	not detected
Caudate putamen	tissue	4.2
Frontal cortex	tissue	4.0
Pituitary gland	tissue	3.9
Medulla oblongata	tissue	3.8
Locus coeruleus	tissue	3.8
Hippocampal formation	tissue	3.5
Ventral forebrain	tissue	3.5
Colon	tissue	3.3	not detected
Entorhinal cortex	tissue	3.2
Urinary bladder	tissue	3.1	not detected
Postcentral gyrus	tissue	2.9
Pons	tissue	2.8
Small intestine	tissue	2.8	not detected
Duodenum	tissue	2.8	not detected
Vagina	tissue	2.6	not detected
Rectum	tissue	2.6	not detected
Thalamus	tissue	2.6
Cervix	tissue	2.5	not detected
Seminal vesicle	tissue	2.5	not detected
Midbrain	tissue	2.4
Tonsil	tissue	2.3	not detected
Olfactory bulb	tissue	2.3
Cerebral cortex	tissue	2.2	not detected
Skeletal muscle	tissue	2.2	not detected
Smooth muscle	tissue	2.2	not detected
Temporal cortex	tissue	2.2
Appendix	tissue	2.1	not detected
Breast	tissue	2.0	not detected
Testis	tissue	2.0	not detected
Gallbladder	tissue	1.9	not detected
Adrenal gland	tissue	1.9	not detected
Esophagus	tissue	1.8	not detected
Endometrium 1	tissue	1.8	not detected
Somatosensory cortex	tissue	1.8
Salivary gland	tissue	1.7	not detected
Motor cortex	tissue	1.7
Liver	tissue	1.7	not detected
Septum	tissue	1.7
Hypothalamus	tissue	1.6
Cerebellum	tissue	1.6	not detected
Amygdala	tissue	1.5
Prostate	tissue	1.5	not detected
Retrosplenial and cingulate cortex	tissue	1.5
Lymph node	tissue	1.4	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Area parastriata, superior (9.9), Nucleus basalis of Meynert (8.7), Posterior thalamic nucleus (8.7), Dorsal spinal cord (8.1), Caudate nucleus (7.9).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets:

Target	Regulation
ALPL	Activation
ATOH8	Activation
BMP2	Activation
CYBRD1	Repression
HAMP	Activation
ID1	Activation
SLC11A2	Repression
SLC40A1	Repression
SMAD7	Activation
SPP1	Activation
TNFRSF11B	Activation

Upstream regulators (CollecTRI, top): ESR1, ESR2, ETV7, HAMP, HJV, SMAD4, SP1, TMPRSS6

miRNA regulators (miRDB)

Targeting BMP6 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 72 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-3714	99.71	70.74	2671

Functional genomics

gnomAD constraint: pLI 0.943, LOEUF 0.523, missense Z -0.685 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000283147 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈12% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
6:7,726,956–7,879,088	650 / 556.3	1.17	no
6:7,879,089–7,880,210	27 / 80.1	0.34	yes (p 3.0e-09)
6:7,880,211–7,880,340	43 / 54.0	0.80	no

Literature-anchored findings (GeneRIF, showing 40)

• the presence of BMP-6 in adult human articular cartilage indicates a functional role for this growth factor in the maintenance of joint integrity. (PMID:13130469)
• BMP-2 and BMP-6 are expressed in arthritic synovium and are strongly up-regulated by proinflammatory cytokines. (PMID:14558086)
• results revealed a novel potent effect of PTH and vitamin D(3) plus BMPs in inducing bone development by human mesenchymal stem cells (PMID:15186723)
• BMP-6 increases the levels of osteopontin, BMP-2, alkaline phosphatase and core binding factor alpha 1 mRNAs in human periodontal (HPL) ligament cells. (PMID:15516325)
• Recombinant noggin inhibited the function of BMP-6, suggesting a negative feedback regulation of BMP activity and indicating a strategy for the development of a novel therapeutic target in treatment of osteosclerotic bone metastases of prostate cancer (PMID:15548695)
• several single nucleotide polymorphisms in bone morphogenic protein 6, annexin A2, and klotho were associated with sickle cell osteonecrosis (PMID:15784727)
• To analyze the expression of bone morphogenetic proteins (BMPs) in prostate and breast cancers with established metastasis in bone (PMID:15861517)
• In mature human B cells, BMP-6 inhibited cell growth, and rapidly induced phosphorylation of Smad1/5/8 followed by an upregulation of Id1. (PMID:15877825)
• endogenous BMP-6 system plays critical roles in aldosterone production between Ang II and K through ERK signaling pathway. (PMID:16527843)
• Excess numbers of BMP6-deficient myofibroblast progenitor cells may favour adverse tissue remodelling in patients with diabetes. (PMID:16547600)
• a distinct BMP and TGFbeta-receptor repertoire may explain the reduced chondrogenic capacity of adipose tissue stromal cells in vitro (PMID:17238135)
• strong BMP staining is seen in maturing chondrocytes, and thus may play a role in chondrocyte differentiation and/or apoptosis; BMP release by osteoclasts may promote osteoblastic differentiation at sites of bone remodeling (PMID:17262821)
• BMP-6 promoter methylation status is correlated with estrogen receptor status in breast cancer (PMID:17574840)
• BMP-6 promoter methylation may be a potential new biomarker of risk prediction in DLBCL. (PMID:17575215)
• Data show that pcDNA-BMP2/6 produced more rhBMP6 than pcDNA-BMP6. (PMID:17577985)
• BMP6 induced cell cycle arrest in estrogen-insensitive breast cancer cells. BMP6 inhibits stress-induced apoptosis via both Smad and p38 signal pathways. (PMID:17879955)
• A functional bone morphogenetic protein 6 (BMP-6) signalling pathway is present in adult pre-T-leukemia lymphoma cell line Jurkat TAg. (PMID:17899540)
• presents the crystal structure of BMP-6 (PMID:17924656)
• The crystal structure of human BMP-6 was determined to a resolution of 2.1 A. (PMID:18070108)
• Affects aldosterone breakthrough induced by long-term treatment with agtr1 stimulated aldosterone production by adrenocortical cells. (PMID:18308844)
• BMP-2, BMP-4, and BMP-6 are endogenous ligands for Hemojuvelin in hepatoma-derived cell lines, and all 3 of these ligands are expressed in human liver (PMID:18326817)
• Expression of BMP1, BMP6, BMP7, and BMP-receptor 2 was significantly increased in advanced stages of myelofibrosis compared and enhanced levels of BMP6 expression were already evident in prefibrotic stages of primary myelofibrosis. (PMID:18349123)
• BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells (PMID:18436533)
• Wnt3a and Wnt5a have roles in inducing BMP-4 and 6 expression in prostate cancer osteoblast differentiation (PMID:18632632)
• BMP signaling plays a role in the induction of an osteoblastic phenotype in human dermal fibroblasts in response to vitamin D(3) stimulation (PMID:18683889)
• BMP-6 promoter methylation is likely to be a common epigenetic event at later stages of ATL and that the methylation profiles may be useful for the staging of ATL as well as for evaluation of the individual risk of developing the disease. (PMID:18688853)
• significant role of BMP-6 in inhibiting MDA-MB-231 migration through decreasing deltaEF1 expression which subsequently relieves deltaEF1-mediated invasion. (PMID:18805502)
• the potential use of bone-morphogenetic protein-6, noggin and sclerostin expression together as a prognostic predictor for metastatic progression of prostate cancer. (PMID:18931653)
• BMP3b and BMP6 genes were suppressed by DNA methylation and methylation of BMP3b is significantly frequent in Japanese malignant pleural mesotheliomas (MPMs), suggesting its pathogenic role and the ethnic difference in MPMs. (PMID:18949431)
• S1P induces osteoblast precursor recruitment and promotes mature cell survival. Wnt10b and BMP6 also were significantly increased in mature osteoclasts, whereas sclerostin levels decreased during differentiation. (PMID:19075223)
• study confirmed association of a single SNP, BMP6-3 (rs3812163), suggesting a potential role for BMP6 in the development of sickle avascular necrosis in sickle cell disease patients. (PMID:19093115)
• attenuates oxidant injury in kidney cells via Smad-dependent HO-1 induction (PMID:19245827)
• Mtations in BMP6 mayause iron overload in humans with severe juvenile hemochromatosia. (PMID:19252488)
• Bone morphogenetic protein-6 may function as an anti-metastasis factor by a mechanism involving transcriptional repression of microRNA-21 in breast cancer. (PMID:19308091)
• BMP-6 is an important mediator to support healthy follicle growth in the human ovary. (PMID:19539911)
• Data show that bone morphogenetic protein 6 ameliorates TGF-beta1-induced changes in HK-2 cells. (PMID:19543302)
• A high BMP6 expression in primary myeloma cell samples delineates significantly superior overall survival for patients undergoing high-dose chemotherapy (PMID:19718049)
• regulates hepcidin an iron metabolism in humans (PMID:19765379)
• Malignant human clear cell renal carcinoma tissue had significantly higher BMP-6 mRNA expression than healthy tissue (PMID:20016212)
• Using BMP-6/7 chimeras, we identified lysine 60 as a key residue conferring noggin resistance within the BMP-6 protein. (PMID:20048150)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bmp6	ENSDARG00000015686
mus_musculus	Bmp6	ENSMUSG00000039004
rattus_norvegicus	Bmp6	ENSRNOG00000013717

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), INHA (ENSG00000123999), BMP4 (ENSG00000125378), BMP2 (ENSG00000125845), GDF5 (ENSG00000125965), GDF1 (ENSG00000130283), BMP15 (ENSG00000130385), GDF15 (ENSG00000130513), GDF11 (ENSG00000135414), MSTN (ENSG00000138379), INHBE (ENSG00000139269), LEFTY2 (ENSG00000143768), GDF7 (ENSG00000143869), BMP3 (ENSG00000152785), GDF6 (ENSG00000156466), NODAL (ENSG00000156574), INHBB (ENSG00000163083), BMP10 (ENSG00000163217), GDF9 (ENSG00000164404), INHBC (ENSG00000175189), BMP8A (ENSG00000183682), GDF3 (ENSG00000184344), LEFTY1 (ENSG00000243709), GDF2 (ENSG00000263761), GDF10 (ENSG00000266524)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88182) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 22 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	2
kyphosis	1
abnormal salivary gland morphology	1
decreased body length	1
decreased body size	1
increased anxiety-related response	1
decreased locomotor activity	1
abnormal pancreas morphology	1
abnormal skin morphology	1
abnormal brain morphology	1
increased mean corpuscular volume	1
increased circulating alanine transaminase level	1
abnormal spine curvature	1
increased brain size	1
decreased heart rate	1
increased circulating aspartate transaminase level	1
increased mean corpuscular hemoglobin	1
increased hemoglobin content	1
increased mean corpuscular hemoglobin concentration	1
abnormal sternum ossification	1
abnormal sternum manubrium morphology	1
increased circulating iron level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo pygmaeus	A1C2U3	100.0%	Diamond
Macaca mulatta	A1C2U6	100.0%	Diamond
Pan paniscus	A1C2U7	100.0%	Diamond
Pan troglodytes	A1C2V0	100.0%	Diamond
Gorilla gorilla gorilla	A1C2V5	100.0%	Diamond
Ovis aries	O18830	100.0%	Diamond
Bos taurus	O18836	100.0%	Diamond
Bos indicus	Q5RZV4	100.0%	Diamond
Hemitragus jemlahicus	Q5USV8	100.0%	Diamond
Bos gaurus	Q5USW1	100.0%	Diamond
Capra hircus	Q6T5B8	100.0%	Diamond
Macaca fascicularis	Q95J86	100.0%	Diamond
Papio hamadryas	O18828	99.7%	Diamond
Capra ibex	Q5USV9	99.7%	Diamond
Vulpes vulpes	Q6DTL9	99.5%	Diamond
Vulpes lagopus	Q6J1J2	99.5%	Diamond
Gallus gallus	O42220	99.2%	Diamond
Meleagris gallopavo	O42221	99.2%	Diamond
Canis lupus familiaris	Q6UKZ8	99.2%	Diamond
Coturnix coturnix	Q8AVB2	99.2%	Diamond
Excalfactoria chinensis	Q8UWD7	99.2%	Diamond
Sylvicapra grimmia	Q5USV6	98.9%	Diamond
Xenopus tropicalis	Q800B9	98.8%	Diamond
Taurotragus derbianus	Q5USW0	98.7%	Diamond
Bubalus bubalis	Q6X5V1	98.7%	Diamond
Drosophila melanogaster	P07713	98.3%	Diamond
Drosophila simulans	P91706	98.3%	Diamond
Sus scrofa	O18831	98.1%	Diamond
Anas platyrhynchos	Q8UWE0	98.1%	Diamond
Equus caballus	Q9GM97	98.1%	Diamond
Suncus murinus	Q8MJV5	98.0%	Diamond
Anser anser anser	Q8UWD9	97.9%	Diamond
Dama dama	Q29607	97.8%	Diamond
Antilocapra americana	Q5USV5	97.6%	Diamond
Aepyceros melampus	Q5USV7	97.3%	Diamond
Columba livia	Q8UWD8	97.3%	Diamond
Lepus capensis	Q8HY52	96.8%	Diamond
Oryctolagus cuniculus	O46564	95.7%	Diamond
Xenopus laevis	Q91609	94.0%	Diamond
Felis catus	Q6X2S4	93.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SCARNA27	ncRNA	100124533
EEF1E1-BLOC1S5	ncRNA	100526837
BLOC1S5	protein-coding	63915
TXNDC5	protein-coding	81567
EEF1E1	protein-coding	9521
BLOC1S5-TXNDC5	ncRNA	100526836
SNRNP48	protein-coding	154007
DSP-AS1	ncRNA	101928076
DSP	protein-coding	1832

Protein

Protein identifiers

Bone morphogenetic protein 6 — P22004 (reviewed: P22004)

Alternative names: VG-1-related protein

All UniProt accessions (1): P22004

UniProt curated annotations — full annotation on UniProt →

Function. Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes including cartilage and bone formation. Also plays an important role in the regulation of HAMP/hepcidin expression and iron metabolism by acting as a ligand for hemojuvelin/HJV. Also acts to promote expression of HAMP, potentially via the interaction with its receptor BMPR1A/ALK3. Initiates the canonical BMP signaling cascade by associating with type I receptor ACVR1 and type II receptor ACVR2B. In turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target. Can also signal through non-canonical pathway such as TAZ-Hippo signaling cascade to modulate VEGF signaling by regulating VEGFR2 expression.

Subunit / interactions. Interacts with SOSTDC1. Interacts (when glycosylated) with type I receptor ACVR1; the interaction may induce HAMP expression. Interacts with type II receptor ACVR2B. Interacts with Hemojuvelin/HJV. Interacts with ERFE; the interaction inhibits BMP-induced transcription of HAMP. Interacts with BMPR1A/ALK3. Forms heterodimers with BMP2 in vitro; the heterodimer then binds to its receptor BMPR1A /ALK3 and may induce HAMP expression.

Subcellular location. Secreted.

Post-translational modifications. Glycosylated at Asn-454. Glycosylation is crucial for recognition by the activin receptor type I/ACVR1.

Disease relevance. Iron overload (IO) [MIM:620121] A disorder of iron homeostasis with incomplete and age-dependent penetrance. It is characterized by adult onset of increased hepatic and systemic iron levels, increased serum ferritin, normal or high transferrin saturation, and inappropriately low or normal levels of hepcidin. The severity of the phenotype depends on age, sex, as well as additional genetic or acquired factors including alcohol consumption and increased body weight. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_001709* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001111	TGF-b_propeptide	Domain
IPR001839	TGF-b_C	Domain
IPR015615	TGF-beta-like	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019, PF00688

UniProt features (41 total): sequence variant 10, strand 7, glycosylation site 5, disulfide bond 4, region of interest 4, helix 3, turn 3, compositionally biased region 2, signal peptide 1, propeptide 1, chain 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
2R53	Crystal structure analysis of Bone Morphogenetic Protein-6 variant B2 (B2-BMP-6)	X-RAY DIFFRACTION	2.1
2QCW	Crystal Structure of Bone Morphogenetic Protein-6 (BMP-6)	X-RAY DIFFRACTION	2.49
2R52	Crystal structure analysis of Bone Morphogenetic Protein-6 (BMP-6)	X-RAY DIFFRACTION	2.5
6OMO	Human BMP6 homodimer	X-RAY DIFFRACTION	2.8
9N4K	CryoEM structure of ALK2-ActRIIB bound to BMP6	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22004-F1	69.74	0.32

Human Protein Atlas

Protein class: Predicted secreted proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

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

Disulfide bonds (4)

Type	Positions
Disulfide bond	412–478, 441–510, 445–512
Interchain	477

Glycosylation sites (5)

Type	Positions
N-linked (glcnac…) asparagine	269, 386, 404, 454, 241

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 526 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, RNGTGGGC_UNKNOWN, GOBP_EPITHELIUM_DEVELOPMENT, ZHAN_LATE_DIFFERENTIATION_GENES_UP, BENPORATH_ES_WITH_H3K27ME3, CHIBA_RESPONSE_TO_TSA_UP, TSENG_IRS1_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_DIFFERENTIATION, GOBP_CARTILAGE_DEVELOPMENT, KEGG_HEDGEHOG_SIGNALING_PATHWAY, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT

GO Biological Process (46): negative regulation of transcription by RNA polymerase II (GO:0000122), skeletal system development (GO:0001501), osteoblast differentiation (GO:0001649), eye development (GO:0001654), kidney development (GO:0001822), positive regulation of endothelial cell proliferation (GO:0001938), type B pancreatic cell development (GO:0003323), intracellular iron ion homeostasis (GO:0006879), inflammatory response (GO:0006954), immune response (GO:0006955), heart development (GO:0007507), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), response to activity (GO:0014823), positive regulation of bone mineralization (GO:0030501), BMP signaling pathway (GO:0030509), positive regulation of lipopolysaccharide-mediated signaling pathway (GO:0031666), response to magnesium ion (GO:0032026), positive regulation of chondrocyte differentiation (GO:0032332), positive regulation of aldosterone biosynthetic process (GO:0032349), response to retinoic acid (GO:0032526), positive regulation of vascular permeability (GO:0043117), positive regulation of endothelial cell differentiation (GO:0045603), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of epithelial cell proliferation (GO:0050679), positive regulation of protein secretion (GO:0050714), cartilage development (GO:0051216), response to glucocorticoid (GO:0051384), bone development (GO:0060348), positive regulation of SMAD protein signal transduction (GO:0060391), multicellular organismal-level iron ion homeostasis (GO:0060586), cellular response to mechanical stimulus (GO:0071260), cellular response to iron ion (GO:0071281), cellular response to BMP stimulus (GO:0071773), positive regulation of intracellular signal transduction (GO:1902533), negative regulation of adherens junction organization (GO:1903392), negative regulation of cell-cell adhesion mediated by cadherin (GO:2000048), positive regulation of aldosterone secretion (GO:2000860), ossification (GO:0001503), tissue development (GO:0009888), response to iron ion (GO:0010039), cell differentiation (GO:0030154), regulation of cell population proliferation (GO:0042127), cell development (GO:0048468), positive regulation of developmental process (GO:0051094)

GO Molecular Function (5): cytokine activity (GO:0005125), growth factor activity (GO:0008083), protein heterodimerization activity (GO:0046982), BMP receptor binding (GO:0070700), protein binding (GO:0005515)

GO Cellular Component (3): vesicle (GO:0031982), protein-containing complex (GO:0032991), extracellular region (GO:0005576)

GO top-level categories

55 GO namespaces:

Category	Terms
animal organ development	2
response to stimulus	2
receptor ligand activity	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
system development	1
animal gross anatomical part developmental process	1
ossification	1
cell differentiation	1
sensory organ development	1
visual system development	1
renal system development	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
epithelial cell development	1
type B pancreatic cell differentiation	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
defense response	1
immune system process	1
circulatory system development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
positive regulation of response to biotic stimulus	1
positive regulation of signal transduction	1
lipopolysaccharide-mediated signaling pathway	1
regulation of lipopolysaccharide-mediated signaling pathway	1
positive regulation of response to external stimulus	1
response to metal ion	1
chondrocyte differentiation	1
regulation of chondrocyte differentiation	1
positive regulation of cell differentiation	1
positive regulation of cartilage development	1
aldosterone biosynthetic process	1
regulation of aldosterone biosynthetic process	1
positive regulation of steroid hormone biosynthetic process	1
positive regulation of alcohol biosynthetic process	1
protein dimerization activity	1
transmembrane receptor protein serine/threonine kinase binding	1
binding	1
membrane-bounded organelle	1
cellular_component	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 21 of 55 annotations. The rest are phylogenetic / computational / electronic (IEA).

21 experimentally-supported GO terms:

GO term	NS	Evidence
BMP signaling pathway	BP	direct assay
bone development	BP	direct assay
cellular response to BMP stimulus	BP	mutant phenotype
immune response	BP	mutant phenotype
intracellular iron ion homeostasis	BP	direct assay
multicellular organismal-level iron ion homeostasis	BP	mutant phenotype
negative regulation of adherens junction organization	BP	direct assay
negative regulation of cell-cell adhesion mediated by cadherin	BP	direct assay
positive regulation of SMAD protein signal transduction	BP	direct assay
positive regulation of aldosterone biosynthetic process	BP	direct assay
positive regulation of bone mineralization	BP	direct assay
positive regulation of epithelial cell proliferation	BP	direct assay
positive regulation of gene expression	BP	mutant phenotype
positive regulation of intracellular signal transduction	BP	direct assay
positive regulation of osteoblast differentiation	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of vascular permeability	BP	direct assay
type B pancreatic cell development	BP	direct assay
protein-containing complex	CC	direct assay
BMP receptor binding	MF	direct assay
protein heterodimerization activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,346 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BMP6	HJV	Q6ZVN8	924
BMP6	HAMP	P81172	888
BMP6	BMPR1A	P36894	866
BMP6	BMPR2	Q13873	852
BMP6	NOG	Q13253	835
BMP6	BMPR1B	P78366	821
BMP6	TMPRSS6	Q8IU80	818
BMP6	HFE	Q30201	807
BMP6	BGLAP	P02818	771
BMP6	SMAD5	Q99717	767
BMP6	ACVR1	Q04771	740
BMP6	GREM2	Q9H772	738
BMP6	SOST	Q9BQB4	735
BMP6	BMPER	Q8N8U9	733
BMP6	TFR2	Q9UP52	729

IntAct

Human interaction partners of BMP6 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
TNFAIP6	direct interaction	0.440	1
SNX2	association	0.350	1

BioGRID (18 interactions; top human partners by supporting records): ACVR2A (Reconstituted Complex; 2 records), BMPR1A (Reconstituted Complex; 2 records), ACVR1 (Reconstituted Complex), ACVR2B (Affinity Capture-Western), AGO2 (Affinity Capture-RNA), ANKRD50 (Affinity Capture-MS), APPBP2 (Affinity Capture-MS), BMPR1B (Reconstituted Complex), BMPR2 (Affinity Capture-Western), DDX39A (Affinity Capture-RNA), SNX1 (Affinity Capture-MS), SNX2 (Affinity Capture-MS), SNX6 (Affinity Capture-MS), TDGF1 (Reconstituted Complex), TGOLN2 (Proximity Label-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ ACVR1-BMP6-BMPR1A complex	3	ACVR1, BMP6, BMPR1A

Ligand–receptor pairs (CellPhoneDB) (9)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

9 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
BMPR1A;BMPR2	ligand	Signaling by BMP
ACVR1;BMPR2	ligand	Signaling by BMP
ACVR1;ACVR2A	ligand	Signaling by BMP
ACVR1;ACVR2B	ligand	Signaling by BMP
BMPR1B;ACVR2A	ligand	Signaling by BMP
BMPR1A;ACVR2A	ligand	Signaling by BMP
BMPR1A;ACVR2B	ligand	Signaling by BMP
BMPR1B;BMPR2	ligand	Signaling by BMP
BMPR1B;ACVR2B	ligand	Signaling by BMP

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PRAD.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for BMP6: 139 ClinVar records (2 pathogenic / likely pathogenic); 37 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	94
Likely benign	20
Benign	11

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
929751	NM_001718.6(BMP6):c.409C>A (p.Leu137Met)	Likely pathogenic	criteria provided, single submitter	1
253526	GRCh37/hg19 6p25.3-22.3(chr6:168775-24023234)x3	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore BMP6’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 891):

Position(s)	Effect	Δscore	Sites
6:7845257	donor_gain	1.0000
6:7845269	donor_gain	1.0000
6:7861449–7861450	acceptor_loss	1.0000	6
6:7879981	acceptor_gain	1.0000
6:7845131	acceptor_gain	0.9900
6:7845137	acceptor_gain	0.9900
6:7845138–7845139	acceptor_loss	0.9900	6
6:7845333–7845334	donor_loss	0.9900	5
6:7861600–7861601	donor_loss	0.9900	5
6:7862295	acceptor_gain	0.9900

AlphaMissense

1,308 missense substitutions predicted likely pathogenic (of 3,354 scored), across 271 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M505	9	0.994	0.999
M453	9	0.937	0.999
M136	9	0.909	0.997
M216	9	0.882	0.985
M79	9	0.860	0.992
F421	8	0.999	1.000
H458	8	0.999	1.000
F447	8	0.996	1.000
N454	8	0.989	0.998
F358	8	0.987	0.999
F240	8	0.980	0.999
H466	8	0.979	0.999
D213	8	0.976	0.996
F218	8	0.974	0.995
D492	8	0.974	0.992
N457	8	0.971	0.999
H513	8	0.968	0.996
F135	8	0.967	0.997
F308	8	0.949	0.997
N496	8	0.949	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.51e-07
Lung Adenocarcinoma (validation)	favorable	8.17e-05

Disease associations

OMIM: gene MIM:112266 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
iron overload, susceptibility to	Moderate	Autosomal dominant	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
iron overload, susceptibility to	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Iron metabolism disorders - NOT common HFE mutations	green

Mondo (2): primary ovarian failure (MONDO:0005387), iron overload, susceptibility to (MONDO:0859316)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

50 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000029	Testicular atrophy
HP:0000044	Hypogonadotropic hypogonadism
HP:0000141	Amenorrhea
HP:0000741	Apathy
HP:0000771	Gynecomastia
HP:0000789	Infertility
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism
HP:0000939	Osteoporosis
HP:0000953	Hyperpigmentation of the skin
HP:0001254	Lethargy
HP:0001324	Muscle weakness
HP:0001369	Arthritis
HP:0001386	Joint swelling
HP:0001387	Joint stiffness
HP:0001394	Cirrhosis
HP:0001402	Hepatocellular carcinoma
HP:0001409	Portal hypertension
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001640	Cardiomegaly
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0002027	Abdominal pain
HP:0002240	Hepatomegaly
HP:0002829	Arthralgia
HP:0003040	Arthropathy
HP:0003074	Hyperglycemia
HP:0003199	Decreased muscle mass
HP:0003281	Increased circulating ferritin concentration
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0005198	Stiff interphalangeal joints
HP:0005978	Type II diabetes mellitus
HP:0007574	Generalized bronze hyperpigmentation
HP:0009830	Peripheral neuropathy
HP:0011031	Abnormality of iron homeostasis
HP:0011675	Arrhythmia
HP:0011911	Abnormal metacarpophalangeal joint morphology
HP:0012378	Fatigue
HP:0012463	Elevated transferrin saturation
HP:0012465	Elevated hepatic iron concentration
HP:0030153	Cholangiocarcinoma
HP:0030848	Elevated jugular venous pressure
HP:0031877	Elevated circulating hepcidin concentration
HP:0040171	Decreased serum testosterone concentration
HP:0046504	Decreased libido
HP:0100626	Chronic hepatic failure
HP:0100639	Erectile dysfunction

GWAS associations

showing 30 of 37 associations:

Study	Trait	p-value
GCST002647_167	Height	4e-38
GCST007429_139	Lung function (FVC)	8e-31
GCST007432_169	FEV1	2e-24
GCST90000025_1051	Appendicular lean mass	3e-24
GCST000817_1	Height	1e-23
GCST007429_10	Lung function (FVC)	2e-22
GCST007432_31	FEV1	1e-19
GCST012227_794	Hip circumference adjusted for BMI	1e-17
GCST001956_1	Height	5e-17
GCST012227_798	Hip circumference adjusted for BMI	4e-14
GCST002483_2	Lung function (forced vital capacity)	6e-13
GCST012226_216	Waist circumference adjusted for body mass index	6e-13
GCST012226_217	Waist circumference adjusted for body mass index	7e-13
GCST008839_466	Height	2e-12
GCST90002407_325	White blood cell count	7e-12
GCST000175_51	Height	2e-11
GCST012227_795	Hip circumference adjusted for BMI	2e-11
GCST90020028_634	Hip circumference adjusted for BMI	2e-11
GCST90020028_635	Hip circumference adjusted for BMI	7e-11
GCST007096_59	Pulse pressure	2e-10
GCST012226_468	Waist circumference adjusted for body mass index	4e-10
GCST012227_797	Hip circumference adjusted for BMI	1e-9
GCST90002390_350	Mean corpuscular hemoglobin	1e-9
GCST004067_109	Hip circumference adjusted for BMI	3e-9
GCST012227_796	Hip circumference adjusted for BMI	4e-9
GCST90002402_601	Platelet count	5e-9
GCST008163_277	Height	8e-9
GCST012616_1	Spondylosis	9e-9
GCST007269_113	Pulse pressure	4e-8
GCST002702_35	Height	1e-7

EFO canonical traits (from GWAS)

10 canonical traits:

EFO ID	Trait name
EFO:0004207	pathological myopia
EFO:0004312	vital capacity
EFO:0008039	BMI-adjusted hip circumference
EFO:0005763	pulse pressure measurement
EFO:0004314	forced expiratory volume
EFO:0007859	response to interferon
EFO:0007789	BMI-adjusted waist circumference
EFO:0004980	appendicular lean mass
EFO:0004527	mean corpuscular hemoglobin
EFO:0004309	platelet count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3286078 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3288258	KD	24000 nM
CHEMBL3288260	KD	34000 nM
CHEMBL3288259	KD	46000 nM

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.05	Kd	9000	nM	CHEMBL3288260

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
nonasodium;(2R,3S,4S,5R,6R)-6-[(2R,3S,4R,5R,6R)-5-acetamido-6-[(2R,3S,4S,5R,6R)-6-[(2R,3S,4R,5R,6R)-6-[(2R,3S,4R,5R,6R)-6-[(2R,3S,4R,5R,6S)-5-acetamido-4-hydroxy-6-pentoxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-2-carboxylato-4,5-dihydroxyoxan-3-yl]oxy-4-hydroxy-5-(sulfonatoamino)-2-(sulfonatooxymethyl)oxan-3-yl]oxy-2-carboxylato-4-hydroxy-5-sulfonatooxyoxan-3-yl]oxy-4-hydroxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,4-dihydroxy-5-sulfonatooxyoxane-2-carboxylate	1152110: Binding affinity to human recombinant BMP6 by surface plasmon resonance assay	kd	9.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	5
sodium arsenite	decreases reaction, increases phosphorylation, increases reaction, affects methylation, decreases phosphorylation (+2 more)	4
Estradiol	affects cotreatment, increases expression, decreases expression	4
Benzo(a)pyrene	increases methylation, decreases expression	3
Particulate Matter	affects expression, decreases expression, increases expression	3
bisphenol A	decreases expression, affects cotreatment	2
cobaltous chloride	decreases reaction, increases expression, decreases expression	2
nickel sulfate	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
dorsomorphin	increases secretion, affects cotreatment, decreases reaction, increases expression	2
Acetaminophen	increases expression, increases secretion	2
Calcitriol	increases expression, increases reaction	2
Deferoxamine	decreases reaction, increases expression, decreases expression, affects reaction	2
Dexamethasone	decreases expression, decreases reaction, increases expression, affects cotreatment	2
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment, increases reaction	2
Progesterone	decreases reaction, increases secretion, affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression, increases reaction, increases expression	2
Tretinoin	increases expression, increases reaction	2
8-Bromo Cyclic Adenosine Monophosphate	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
fulvic acid	decreases reaction, increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
geraniol	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
pirprofen	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3293907	Binding	Binding affinity to human recombinant BMP6 by surface plasmon resonance assay	Synthesis and biological evaluation of a unique heparin mimetic hexasaccharide for structure-activity relationship studies. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7L2	Ubigene A-549 BMP6 KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 75 trials:

NCT	Phase	Status	Title
NCT00417066	Phase 4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	Phase 4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	Phase 4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	Phase 4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	Phase 4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	Phase 4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	Phase 3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	Phase 2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	Phase 2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	Phase 2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	Phase 2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	Phase 2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	Phase 1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	Phase 1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	Phase 1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	Phase 1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	Phase 1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	Phase 2/3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	Phase 2/3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	Phase 1/2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	Phase 1/2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	Phase 1/2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	Phase 1/2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	Phase 1/2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	Phase 1/2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	Phase 1/2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	Phase 1/2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	Phase 1/2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	Phase 1/2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	Phase 1/2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	Phase 1/2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	Phase 1/2	COMPLETED	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	Early Phase 1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	Early Phase 1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	Early Phase 1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00295087	Not specified	COMPLETED	X-Chromosome Inactivation Status and Premature Ovarian Failure
NCT00417157	Not specified	COMPLETED	Modified Natural Cycle Offers a Chance of Pregnancy in Patients With Poor Response and High Basal FSH
NCT00619333	Not specified	UNKNOWN	Inactive FSH in Galactosemia
NCT00780897	Not specified	UNKNOWN	Premature Ovarian Failure (Genetic and Physiopathologic Analysis)
NCT01187524	Not specified	TERMINATED	The Natural History of Reproductive and Overall Health in Girls and Women With a Pre-Mutation in the FMR1 Gene; Creation of a Patient Registry
NCT01411644	Not specified	UNKNOWN	Pheno- & Genotyping POF (WHO III)
NCT02086318	Not specified	UNKNOWN	A New Algorithm to Predict Ovarian Age
NCT02467231	Not specified	ACTIVE_NOT_RECRUITING	Ovarian Reserve After Cancer: Longitudinal Effects
NCT02696889	Not specified	COMPLETED	Rejuvenation of Premature Ovarian Failure With Stem Cells
NCT02779374	Not specified	TERMINATED	Autologous Bone Marrow Transplantation for Premature Ovarian Insufficiency
NCT03207412	Not specified	UNKNOWN	Human Amniotic Epithelial Cells Treatment for Ovarian Insufficiency
NCT03381300	Not specified	ACTIVE_NOT_RECRUITING	Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome
NCT03412487	Not specified	UNKNOWN	Ovarian Histopathology and Laparoscopic Assessment of Premature Ovarian Failure
NCT03474120	Not specified	UNKNOWN	Prospective Genetic Study in Patients With Ovarian Insufficiency
NCT03480412	Not specified	UNKNOWN	Second Step Protocol in Poor Ovarian Responder (POR)
NCT03840824	Not specified	COMPLETED	Blood Spot Self-administered Test and Assay
NCT03861715	Not specified	UNKNOWN	Single Follicular Dexarelix for LH Suppression During Ovarian Stimulation in Oocyte Donors.
NCT03924648	Not specified	COMPLETED	Endocan Levels in Women With Premature Ovarian Insufficiency
NCT04149028	Not specified	COMPLETED	Platelet Rich Plasma Injection Into Ovary of Patients With Premature Ovarian Insufficiency
NCT04189406	Not specified	UNKNOWN	Turner Syndrome Minipuberty Study

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for BMP6 across ~30M SureChEMBL compounds — explore on Sugi Predict.