MEPE

protein-coding

matrix extracellular phosphoglycoprotein, the group of SIBLING family

Gene summary

This gene encodes a secreted calcium-binding phosphoprotein that belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family of proteins. Members of this family are components of the extracellular matrix of bone and dentin and regulate bone mineralization. Deficiency of a similar protein in mouse results in increased bone mass. Mice lacking this gene are resistant to aging-related trabecular bone loss. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

MANE transcript

NM_020203.6

Inheritance

ClinVar variants

P:1U:93B:29

Top phenotype

MEPE-related disorder

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr4:87,821,398-87,846,814

External References & Databases

Ensembl (ENSG00000152595)

Transcript & Mutation Effects

hg38 • Region Span ~25.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nonsyndromic genetic hearing lossMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0019497

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MEPE variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 83

MEPE-related disorderTotal: 55

not providedTotal: 8

OtosclerosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020203.6. 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				8 clinvar	1 clinvar	9
missense			91 clinvar	11 clinvar	9 clinvar	111
nonsense						0
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	93	19	10	123

Highest pathogenic variant AF is 0.00065762154

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020203.6	RefSeq	NP_064588.1	3	MANE Select
ENST00000361056.4	Ensembl	ENSP00000354341.3	3	MANE Select
NM_001184694.3	RefSeq	NP_001171623.1	3	Standard
NM_001184695.4	RefSeq	NP_001171624.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein phosphorylation
Post-translational protein modification
Metabolism of proteins
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

Biological Process

skeletal system development
biomineral tissue development
post-translational protein modification
cellular protein metabolic process

Molecular Function

extracellular matrix structural constituent
protein binding
extracellular matrix protein binding

Cellular Component

endoplasmic reticulum lumen
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000424957
Coding exons: 3
Length: 25407
Individuals with no LoFs: 125635
Homozygous LoFs: 0
Heterozygous LoFs: 77
Defined: 125712
p: 0.000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.188	268	277	0.968	0.0000132	3546
Missense (PolyPhen)		50	55.167	0.90634		790
Synonymous	0.827	87	97.4	0.893	0.00000488	935
Loss of Function	1.06	4	7.03	0.569	3.82e-7	81

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00055	0.00055	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes renal phosphate excretion and inhibits intestinal phosphate absorption (PubMed:14962809, PubMed:19005008). Promotes bone mineralization by osteoblasts and cartilage mineralization by chondrocytes (PubMed:18162525, PubMed:19998030, PubMed:22766095). Regulates the mineralization of the extracellular matrix of the craniofacial complex, such as teeth, bone and cartilage (By similarity). Promotes dental pulp stem cell proliferation and differentiation (PubMed:22341070). {ECO:0000250|UniProtKB:Q8K4L6, ECO:0000269|PubMed:14962809, ECO:0000269|PubMed:18162525, ECO:0000269|PubMed:19005008, ECO:0000269|PubMed:19998030, ECO:0000269|PubMed:22341070, ECO:0000269|PubMed:22766095}.;

Recessive Scores

pRec: 0.156

Intolerance Scores

LoFtool: 0.975
RVIS EVS: 1.67
RVIS percentile EVS: 96.29

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00706

Gene Damage Prediction

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