MESD

mesoderm development LRP chaperone

Basic information

Region (hg38): 15:80946289-80989828

Previous symbols: [ "MESDC2" ]

Links

ENSG00000117899 ∙ NCBI:23184 ∙ OMIM:607783 ∙ HGNC:13520 ∙ Uniprot:Q14696 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta type 2 (Supportive), mode of inheritance: AD
• osteogenesis imperfecta, type 20 (Strong), mode of inheritance: AR
• osteogenesis imperfecta, type 20 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type XX	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dental; Musculoskeletal	31564437; 33596325

ClinVar

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

• not_provided (58 variants)
• not_specified (41 variants)
• Osteogenesis_imperfecta,_type_20 (5 variants)
• MESD-related_disorder (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MESD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015154.3. 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				22	2	24
missense			49	6	2	57
nonsense	2					2
start loss						0
frameshift	3	2				5
splice donor/acceptor (+/-2bp)						0
Total	5	2	49	28	4

Highest pathogenic variant AF is 0.0000117746795

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MESD	protein_coding	protein_coding	ENST00000261758	3	42553

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.628	0.366	125741	0	6	125747	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.373	149	137	1.09	0.00000715	1523
Missense in Polyphen		46	49.986	0.92026		567
Synonymous	-1.53	69	54.6	1.26	0.00000305	458
Loss of Function	2.18	1	7.40	0.135	3.13e-7	92

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.0000550	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.0000550	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Chaperone specifically assisting the folding of beta- propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). Acts as a modulator of the Wnt pathway through chaperoning the coreceptors of the canonical Wnt pathway, LRP5 and LRP6, to the plasma membrane. Essential for specification of embryonic polarity and mesoderm induction. Plays an essential role in neuromuscular junction (NMJ) formation by promoting cell- surface expression of LRP4 (By similarity). May regulate phagocytosis of apoptotic retinal pigment epithelium (RPE) cells (By similarity). {ECO:0000250|UniProtKB:Q9ERE7, ECO:0000269|PubMed:15014448, ECO:0000269|PubMed:17488095}.
• Pathway: Wnt (Consensus)

Recessive Scores

• pRec: 0.117

Intolerance Scores

• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.142
• hipred: Y
• hipred_score: 0.816
• ghis: 0.599

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Mesd
• Phenotype: embryo phenotype

Gene ontology

• Biological process: protein folding;phagocytosis;mesoderm development;Wnt signaling pathway;protein localization to cell surface;positive regulation of skeletal muscle acetylcholine-gated channel clustering
• Cellular component: cellular_component;endoplasmic reticulum;plasma membrane
• Molecular function: molecular_function;identical protein binding;low-density lipoprotein particle receptor binding