BMP6

bone morphogenetic protein 6, the group of Bone morphogenetic proteins

Basic information

Region (hg38): 6:7726098-7881728

Previous symbols: [ "VGR" ]

Links

ENSG00000153162 ∙ NCBI:654 ∙ OMIM:112266 ∙ HGNC:1073 ∙ Uniprot:P22004 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemochromatosis type 5 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Iron overload, susceptibility to	AD/AR	Gastrointestinal	The condition may involve increased risk of liver dysfunction, and awareness may allow preventative measures such as avoidance of other risk factors for hepatic dysfunction	Gastrointestinal	26582087; 28335084; 32464486

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BMP6 gene.

• Inborn genetic diseases (28 variants)
• not provided (6 variants)
• Iron overload, susceptibility to (3 variants)
• Premature ovarian failure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BMP6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense		1	27	3	1	32
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	1	27	6	1

Variants in BMP6

This is a list of pathogenic ClinVar variants found in the BMP6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-7727022-G-A		not specified	Uncertain significance (Jun 18, 2021)
6-7727038-G-A		BMP6-related disorder	Benign (Jan 02, 2020)
6-7727052-G-A		not specified	Uncertain significance (Dec 05, 2023)
6-7727124-C-T		not specified	Uncertain significance (Aug 12, 2021)
6-7727166-C-G		not specified	Uncertain significance (Dec 02, 2022)
6-7727180-G-A		BMP6-related disorder	Benign (Feb 22, 2019)
6-7727194-A-C		not specified	Uncertain significance (Jun 12, 2023)
6-7727220-C-T		not specified	Uncertain significance (Dec 14, 2023)
6-7727235-C-T		not specified	Uncertain significance (Mar 28, 2022)
6-7727238-C-T		Iron overload, susceptibility to	Likely benign (Aug 01, 2022)
6-7727239-C-T		not specified	Uncertain significance (Sep 12, 2023)
6-7727242-T-C		Iron overload, susceptibility to	Likely benign (Feb 01, 2024)
6-7727244-C-T		not specified	Uncertain significance (Jun 24, 2022)
6-7727289-G-C		Iron overload, susceptibility to	risk factor (Nov 28, 2022)
6-7727289-G-GAGC		BMP6-related disorder	Benign (Dec 24, 2019)
6-7727292-C-G		Iron overload, susceptibility to • BMP6-related disorder	Benign/Likely benign (Dec 01, 2022)
6-7727294-G-A		BMP6-related disorder	Benign (Mar 12, 2019)
6-7727325-C-T		not specified	Uncertain significance (Mar 23, 2022)
6-7727364-C-A		Premature ovarian failure	Likely pathogenic (Mar 02, 2020)
6-7727382-C-G		not specified	Uncertain significance (Jul 06, 2022)
6-7727394-A-G		not specified	Likely benign (Apr 15, 2022)
6-7727395-A-G		not specified	Uncertain significance (Nov 08, 2022)
6-7727405-C-G		not specified	Uncertain significance (Oct 05, 2023)
6-7727408-G-T			Likely benign (Aug 01, 2023)
6-7727410-C-A		not specified	Uncertain significance (Mar 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BMP6	protein_coding	protein_coding	ENST00000283147	7	154626

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.759	0.241	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.03	315	268	1.18	0.0000153	3306
Missense in Polyphen		130	128.12	1.0147		1444
Synonymous	-0.660	120	111	1.08	0.00000657	1020
Loss of Function	3.59	4	22.3	0.180	0.00000122	239

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Induces cartilage and bone formation.
• Pathway: TGF-beta signaling pathway - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);TGF-Core;Vitamin D Receptor Pathway;Hfe effect on hepcidin production;Endochondral Ossification;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;TGF-beta super family signaling pathway canonical;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;BMP receptor signaling;GPCR signaling-G alpha i;BMP2 signaling TGF-beta MV;BMP signaling Dro (Consensus)

Recessive Scores

• pRec: 0.373

Intolerance Scores

• loftool: 0.0702
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.56

Haploinsufficiency Scores

• pHI: 0.743
• hipred: Y
• hipred_score: 0.777
• ghis: 0.498

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.936

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Bmp6
• Phenotype: growth/size/body region phenotype; reproductive system phenotype; skeleton phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;skeletal system development;osteoblast differentiation;eye development;kidney development;positive regulation of endothelial cell proliferation;endochondral ossification;type B pancreatic cell development;cellular iron ion homeostasis;inflammatory response;immune response;positive regulation of cell population proliferation;regulation of signaling receptor activity;positive regulation of pathway-restricted SMAD protein phosphorylation;response to activity;positive regulation of bone mineralization;BMP signaling pathway;male genitalia development;positive regulation of lipopolysaccharide-mediated signaling pathway;response to magnesium ion;positive regulation of chondrocyte differentiation;positive regulation of aldosterone biosynthetic process;response to retinoic acid;regulation of apoptotic process;regulation of MAPK cascade;positive regulation of endothelial cell differentiation;positive regulation of neuron differentiation;positive regulation of osteoblast differentiation;positive regulation of transcription by RNA polymerase II;cell development;positive regulation of epithelial cell proliferation;positive regulation of protein secretion;cartilage development;response to glucocorticoid;positive regulation of SMAD protein signal transduction;SMAD protein signal transduction;multicellular organismal iron ion homeostasis;cellular response to mechanical stimulus;cellular response to iron ion;cellular response to BMP stimulus;positive regulation of aldosterone secretion
• Cellular component: extracellular space;cytoplasm;vesicle
• Molecular function: cytokine activity;transforming growth factor beta receptor binding;growth factor activity;protein heterodimerization activity;BMP receptor binding