MGP

matrix Gla protein, the group of Gla domain containing

Basic information

Region (hg38): 12:14880864-14885857

Links

ENSG00000111341 ∙ NCBI:4256 ∙ OMIM:154870 ∙ HGNC:7060 ∙ Uniprot:P08493 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Keutel syndrome (Definitive), mode of inheritance: AR
• Keutel syndrome (Strong), mode of inheritance: AR
• Keutel syndrome (Supportive), mode of inheritance: AR
• Keutel syndrome (Strong), mode of inheritance: AR
• Keutel syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Keutel syndrome	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	6468443; 3717211; 2515061; 9674914; 9916809; 15810001

ClinVar

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

• not_provided (90 variants)
• Keutel_syndrome (16 variants)
• MGP-related_disorder (7 variants)
• not_specified (3 variants)
• Inborn_genetic_diseases (3 variants)
• Spondyloepiphyseal_dysplasia (1 variants)
• Short_palm (1 variants)
• Short_stature (1 variants)
• Platyspondyly (1 variants)
• Short_distal_phalanx_of_finger (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MGP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000900.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	14		15
missense		2	33	3	1	39
nonsense	1		1			2
start loss						0
frameshift	1		1			2
splice donor/acceptor (+/-2bp)	1	2	3			6
Total	3	4	39	17	1

Highest pathogenic variant AF is 0.000027304164

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MGP	protein_coding	protein_coding	ENST00000228938	5	4746

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125705	0	4	125709	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.116	69	71.8	0.962	0.00000442	826
Missense in Polyphen		30	28.762	1.043		325
Synonymous	-0.201	27	25.7	1.05	0.00000167	227
Loss of Function	0.209	7	7.62	0.918	4.09e-7	88

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Associates with the organic matrix of bone and cartilage. Thought to act as an inhibitor of bone formation.
• Disease: DISEASE: Keutel syndrome (KTLS) [MIM:245150]: An autosomal recessive disorder characterized by abnormal cartilage calcification, peripheral pulmonary stenosis neural hearing loss and midfacial hypoplasia. {ECO:0000269|PubMed:9916809}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Warfarin Pathway, Pharmacodynamics;NOTCH1 regulation of human endothelial cell calcification;Endochondral Ossification;Validated transcriptional targets of AP1 family members Fra1 and Fra2 (Consensus)

Intolerance Scores

• loftool: 0.545
• rvis_EVS: 0.77
• rvis_percentile_EVS: 86.95

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Gene ontology

• Biological process: cartilage condensation;ossification;cell differentiation;regulation of bone mineralization
• Cellular component: extracellular matrix;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: extracellular matrix structural constituent;calcium ion binding;protein binding;structural constituent of bone