MESD

protein-coding

mesoderm development LRP chaperone

Gene summary

Predicted to enable low-density lipoprotein particle receptor binding activity. Involved in ossification and protein folding. Located in cytosol; endoplasmic reticulum; and nuclear body. Implicated in osteogenesis imperfecta type 20. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

MESDC2

MANE transcript

NM_015154.3

Inheritance

AR, AD

ClinVar variants

P:8U:55B:38

Top phenotype

Osteogenesis imperfecta, type XX

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr15:80,946,289-80,989,828

External References & Databases

Ensembl (ENSG00000117899)

Transcript & Mutation Effects

hg38 • Region Span ~43.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

osteogenesis imperfecta, type 20STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032846

Submitter: PanelApp Australia

osteogenesis imperfecta, type 20STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032846

Submitter: Labcorp Genetics (formerly Invitae)

osteogenesis imperfecta, type 20STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032846

Submitter: G2P

osteogenesis imperfecta type 2SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008147

Submitter: Orphanet

Clinical Genomic Database (CGD)

Osteogenesis imperfecta, type XXAR

Manifestation: Dental; Musculoskeletal

Intervention: General

Rationale: 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

Refs: 31564437; 33596325

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MESD variants in ClinVar

4 Conditions Cataloged

not providedTotal: 64

not specifiedTotal: 46

MESD-related disorderTotal: 6

Osteogenesis imperfecta, type 20Total: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015154.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				28 clinvar	2 clinvar	30
missense			55 clinvar	6 clinvar	2 clinvar	63
nonsense	2 clinvar					2
start loss						0
frameshift	4 clinvar	2 clinvar				6
splice donor/acceptor (+/-2bp)						0
Total	6	2	55	34	4	101

Highest pathogenic variant AF is 0.0000117746795

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015154.3	RefSeq	NP_055969.1	3	MANE Select
ENST00000261758.6	Ensembl	ENSP00000261758.4	3	MANE Select
ENST00000422879.3	Ensembl	ENSP00000403839.3	2	Standard
ENST00000559537.1	Ensembl	ENSP00000453220.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Biological Process

protein folding
phagocytosis
mesoderm development
Wnt signaling pathway
protein localization to cell surface

Molecular Function

molecular_function
identical protein binding
low-density lipoprotein particle receptor binding

Cellular Component

cellular_component
endoplasmic reticulum
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261758
Coding exons: 3
Length: 42553
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125747
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.373	149	137	1.09	0.00000715	1523
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000055	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.117

Intolerance Scores

RVIS EVS: -0.27
RVIS percentile EVS: 33.97

Essentials

Essential (gene trap): N