M6PR

protein-coding

mannose-6-phosphate receptor, cation dependent, the group of MRH domain containing

Gene summary

This gene encodes a member of the P-type lectin family. P-type lectins play a critical role in lysosome function through the specific transport of mannose-6-phosphate-containing acid hydrolases from the Golgi complex to lysosomes. The encoded protein functions as a homodimer and requires divalent cations for ligand binding. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A pseudogene of this gene is located on the long arm of chromosome X. [provided by RefSeq, May 2011]

MANE transcript

NM_002355.4

Inheritance

—

ClinVar variants

U:29

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr12:8,940,361-8,949,761

External References & Databases

Ensembl (ENSG00000003056)

Transcript & Mutation Effects

hg38 • Region Span ~9.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to M6PR variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 24

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002355.4. 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			1 clinvar			1
missense			26 clinvar			26
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	29	0	0	29

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002355.4	RefSeq	NP_002346.1	6	MANE Select
ENST00000000412.8	Ensembl	ENSP00000000412.3	6	MANE Select
NM_001207024.2	RefSeq	NP_001193953.1	4	Standard
NM_001414320.1	RefSeq	NP_001401249.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Phagosome - Homo sapiens (human)
Lysosome - Homo sapiens (human)
Lysosome Vesicle Biogenesis
Clathrin derived vesicle budding
trans-Golgi Network Vesicle Budding

Biological Process

protein targeting to lysosome
receptor-mediated endocytosis
endosome to lysosome transport
secretion of lysosomal enzymes
membrane organization

Molecular Function

transmembrane signaling receptor activity
protein binding
mannose binding
protein domain specific binding
retromer complex binding

Cellular Component

lysosomal membrane
endosome
late endosome
trans-Golgi network
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000000412
Coding exons: 6
Length: 9593
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125748
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.979	121	155	0.779	0.00000828	1809
Missense (PolyPhen)		42	72.049	0.58294		797
Synonymous	1.05	47	57.1	0.823	0.00000275	543
Loss of Function	2.24	6	15.5	0.386	9.74e-7	158

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00056	0.00055	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00026	0.00026	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6- phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex.;

Recessive Scores

pRec: 0.790

Intolerance Scores

LoFtool: 0.620
RVIS EVS: -0.16
RVIS percentile EVS: 41.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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