M6PR

Summary

M6PR (mannose-6-phosphate receptor, cation dependent, HGNC:6752) is a protein-coding gene on chromosome 12p13.31, encoding Cation-dependent mannose-6-phosphate receptor (P20645). Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes.

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.

Source: NCBI Gene 4074 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 34 total
• Druggable target: yes
• MANE Select transcript: NM_002355

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6752
Approved symbol	M6PR
Name	mannose-6-phosphate receptor, cation dependent
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	CD-MPR, CD-M6PR
Ensembl gene	ENSG00000003056
Ensembl biotype	protein_coding
OMIM	154540
Entrez	4074

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000000412, ENST00000536844, ENST00000537621, ENST00000539143, ENST00000540837, ENST00000541507, ENST00000543159, ENST00000543258, ENST00000543704, ENST00000543834, ENST00000543845, ENST00000544193, ENST00000544245, ENST00000891555, ENST00000891556, ENST00000891557, ENST00000891558, ENST00000936871, ENST00000936872, ENST00000936873, ENST00000941063, ENST00000941064, ENST00000941065

RefSeq mRNA: 14 — MANE Select: NM_002355 NM_001207024, NM_001414320, NM_001414322, NM_001414323, NM_001414324, NM_001414325, NM_001414327, NM_001414328, NM_001414329, NM_001414330, NM_001414331, NM_001414332, NM_001414333, NM_002355

CCDS: CCDS73440, CCDS8598

Canonical transcript exons

ENST00000000412 — 7 exons

Exon	Start	End
ENSE00000717490	8943405	8943535
ENSE00001348389	8949488	8949645
ENSE00002254457	8940361	8941940
ENSE00003492441	8943801	8943910
ENSE00003523177	8946229	8946405
ENSE00003610229	8942416	8942542
ENSE00003631241	8945418	8945584

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.4585 / max 1644.2747, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129377	56.5473	1823
129375	3.8622	515
129376	3.7959	1437
129379	1.1218	596
129378	0.1313	38

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.72	gold quality
mononuclear cell	CL:0000842	98.60	gold quality
leukocyte	CL:0000738	98.58	gold quality
granulocyte	CL:0000094	98.32	gold quality
islet of Langerhans	UBERON:0000006	97.67	gold quality
spleen	UBERON:0002106	97.63	gold quality
lymph node	UBERON:0000029	97.54	gold quality
rectum	UBERON:0001052	97.54	gold quality
gall bladder	UBERON:0002110	97.51	gold quality
right lung	UBERON:0002167	97.45	gold quality
upper lobe of left lung	UBERON:0008952	97.41	gold quality
mucosa of stomach	UBERON:0001199	97.22	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.97	gold quality
upper lobe of lung	UBERON:0008948	96.97	gold quality
stromal cell of endometrium	CL:0002255	96.94	gold quality
minor salivary gland	UBERON:0001830	96.86	gold quality
left adrenal gland cortex	UBERON:0035825	96.84	gold quality
bone marrow cell	CL:0002092	96.83	gold quality
body of pancreas	UBERON:0001150	96.81	gold quality
left adrenal gland	UBERON:0001234	96.77	gold quality
body of uterus	UBERON:0009853	96.76	gold quality
left lobe of thyroid gland	UBERON:0001120	96.74	gold quality
right adrenal gland cortex	UBERON:0035827	96.66	gold quality
vermiform appendix	UBERON:0001154	96.64	gold quality
left uterine tube	UBERON:0001303	96.63	gold quality
right lobe of thyroid gland	UBERON:0001119	96.57	gold quality
metanephros cortex	UBERON:0010533	96.51	gold quality
lower esophagus	UBERON:0013473	96.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.51	gold quality
right adrenal gland	UBERON:0001233	96.47	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-5061	no	3.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

132 targeting M6PR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-153-5P	99.89	73.86	6317

Literature-anchored findings (GeneRIF, showing 21)

• sorting of the CD-MPR in late endosomes requires a distinct di-aromatic motif with only limited possibilities for variations (PMID:12697764)
• All 5 MPRci-deficient lines resisted infection by cell-free, but not cell-associated, VZV, secreted lysosomal enzymes, and released infectious virions when infected by cell-associated VZV (PMID:15620351)
• We conclude that the CI-MPR participates in lysosomal and granular targeting of serglycin and basic proteins such as lysozyme associated with the proteoglycan in hematopoietic cells. (PMID:17210618)
• sortilin and mannose-6-phosphate receptors recycle to the TGN in SNX1-dependent carriers, which we named endosome-to-TGN transport carriers (PMID:18088323)
• Missorting of cathepsin D in GARP-depleted cells results from accumulation of recycling MPRs in a population of light, small vesicles downstream of endosomes. (PMID:18367545)
• Data demonstrate that Rab31 is required for transport of mannose 6-phosphate receptors from the trans-Golgi network to endosomes and for the Golgi/TGN organization. (PMID:19345684)
• mediates in vitro human immunodeficiency virus and sperm cell interaction (PMID:22015004)
• Mannose receptor (MR) engagement by mesothelin GPI anchor polarizes tumor-associated macrophages and is blocked by anti-MR human recombinant antibody (PMID:22163010)
• Sortilin is a new alpha-Gal A receptor expressed in renal endothelial cells and that this receptor together with the M6PR is able to internalize circulating alpha-Gal A. (PMID:22768187)
• These data indicate that clathrin is required for the function of AP-1- and GGA-coated carriers at the trans-Golgi network but may be dispensable for outward traffic en route to the plasma membrane. (PMID:24407285)
• Results suggest that Rab protein Rab29 is essential for the integrity of the trans-Golgi network (TGN) and participates in the retrograde trafficking of mannose-6-phosphate receptor (M6PR). (PMID:24788816)
• In light of existing report suggesting critical role of Nef-GCC185 interaction reveals valuable mechanistic insights affecting specific protein transport pathway in docking of late endosome derived Rab9 bearing transport vesicle at TGN elucidating role of Nef during viral pathogenesis. (PMID:27105913)
• Most rotavirus strains require the cation-independent mannose-6-phosphate receptor, sortilin-1, and cathepsins to enter cells. (PMID:29275103)
• Mannose-6-phosphate receptor: a novel regulator of T cell immunity. (PMID:29769659)
• Results suggest that, in hormone-responsive breast cancer cells, CD-MPR and cathepsin D are distributed together, and that their expression and distribution are influenced by estradiol. These findings strongly support the involvement of the CD-MPR in the pro-enzyme transport in MCF-7 cells, suggesting the participation of this receptor in the procathepsin D secretion previously reported in breast cancer cells. (PMID:30086159)
• The co-localization of M6PR and of GCC2 with ASOs is influenced by the PS modifications, which have been shown to enhance the affinity of ASOs for proteins, suggesting that localization of these proteins to LEs is mediated by ASO-protein interactions. Reduction of M6PR levels also decreased PS-ASO activity in mouse cells and in livers of mice treated subcutaneously with PS-ASO, indicating a conserved mechanism. (PMID:31840180)
• Monochorionic twins with selective fetal growth restriction: insight from placental whole-transcriptome analysis. (PMID:32437666)
• Golgi-58K can re-localize to late endosomes upon cellular uptake of PS-ASOs and facilitates endosomal release of ASOs. (PMID:34244781)
• Association between genetic variants in oxidative stress-related genes and osteoporotic bone fracture. The Hortega follow-up study. (PMID:34688818)
• Gimap5 promoted RSV degradation through interaction with M6PR. (PMID:36484389)
• Loss of the batten disease protein CLN3 leads to mis-trafficking of M6PR and defective autophagic-lysosomal reformation. (PMID:37400440)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	m6pr	ENSDARG00000018432
mus_musculus	M6pr	ENSMUSG00000007458
rattus_norvegicus	M6pr	ENSRNOG00000014992

Protein

Protein identifiers

Cation-dependent mannose-6-phosphate receptor — P20645 (reviewed: P20645)

Alternative names: 46 kDa mannose 6-phosphate receptor

All UniProt accessions (11): P20645, F5GX30, F5GXE0, F5GXU0, F5H4U1, F5H883, H0YF90, H0YFL0, H0YFY9, H0YGE9, H0YGT2

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homodimer. Binds GGA1, GGA2 and GGA3.

Subcellular location. Lysosome membrane.

Domain organisation. The extracellular domain is homologous to the repeating units (of approximately 147 AA) of the cation-independent mannose 6-phosphate receptor.

Miscellaneous. This receptor has optimal binding in the presence of divalent cations.

RefSeq proteins (14): NP_001193953, NP_001401249, NP_001401251, NP_001401252, NP_001401253, NP_001401254, NP_001401256, NP_001401257, NP_001401258, NP_001401259, NP_001401260, NP_001401261, NP_001401262, NP_002346* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000296	Man-6-P_rcpt_cation_dep	Family
IPR009011	Man6P_isomerase_rcpt-bd_dom_sf	Homologous_superfamily
IPR028927	Man-6-P_rcpt	Family
IPR044865	MRH_dom	Domain

Pfam: PF02157

UniProt features (16 total): glycosylation site 5, disulfide bond 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1JUQ	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20645-F1	84.54	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 267

Disulfide bonds (3): 32–78, 132–167, 145–179

Glycosylation sites (5): 94, 107, 113, 57, 83

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-432720	Lysosome Vesicle Biogenesis
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-199991	Membrane Trafficking
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic

MSigDB gene sets: 280 (showing top): MODULE_52, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_LYSOSOMAL_TRANSPORT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, TGCACTT_MIR519C_MIR519B_MIR519A, MODULE_151, LFA1_Q6, MODULE_45, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_PROTEIN_TARGETING, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_VACUOLAR_TRANSPORT, KEGG_LYSOSOME, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (6): protein targeting to lysosome (GO:0006622), receptor-mediated endocytosis (GO:0006898), lysosomal transport (GO:0007041), endosome to lysosome transport (GO:0008333), secretion of lysosomal enzymes (GO:0033299), glycosphingolipid catabolic process (GO:0046479)

GO Molecular Function (5): transmembrane signaling receptor activity (GO:0004888), protein domain specific binding (GO:0019904), protein transporter activity (GO:0140318), retromer complex binding (GO:1905394), protein binding (GO:0005515)

GO Cellular Component (14): lysosomal membrane (GO:0005765), endosome (GO:0005768), late endosome (GO:0005770), trans-Golgi network (GO:0005802), plasma membrane (GO:0005886), membrane (GO:0016020), transport vesicle (GO:0030133), clathrin-coated endocytic vesicle membrane (GO:0030669), trans-Golgi network membrane (GO:0032588), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), lysosome (GO:0005764), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Membrane Trafficking	3
trans-Golgi Network Vesicle Budding	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Clathrin-mediated endocytosis	1
Glycosphingolipid metabolism	1
Sphingolipid metabolism	1
Vesicle-mediated transport	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
endomembrane system	3
lysosomal transport	2
cytoplasmic vesicle	2
cytoplasm	2
protein targeting to vacuole	1
protein localization to lysosome	1
endocytosis	1
vacuolar transport	1
intercellular transport	1
vesicle-mediated transport	1
protein secretion	1
glycosphingolipid metabolic process	1
glycolipid catabolic process	1
sphingolipid catabolic process	1
signaling receptor activity	1
protein binding	1
transporter activity	1
protein-containing complex binding	1
binding	1
lysosome	1
lytic vacuole membrane	1
endosome	1
Golgi apparatus subcompartment	1
membrane	1
cell periphery	1
clathrin-coated vesicle membrane	1
endocytic vesicle membrane	1
clathrin-coated endocytic vesicle	1
trans-Golgi network	1
organelle membrane	1
intracellular anatomical structure	1
lytic vacuole	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

730 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
M6PR	GGA1	Q9UJY5	921
M6PR	IGF2R	P11717	916
M6PR	GGA2	Q9UJY4	889
M6PR	GGA3	Q9NZ52	847
M6PR	IGF2	P01344	688
M6PR	GOLGA4	Q13439	603
M6PR	ZFYVE26	Q68DK2	579
M6PR	TGOLN2	O43493	571
M6PR	CPD	O75976	567
M6PR	SORT1	Q99523	547
M6PR	CREG1	O75629	542
M6PR	HGS	O14964	537
M6PR	SI	P14410	526
M6PR	LAMP1	P11279	519
M6PR	MGAM	O43451	518

IntAct

61 interactions, top by confidence:

A	B	Type	Score
GGA3	IGF2R	psi-mi:“MI:0915”(physical association)	0.760
GGA3	M6PR	psi-mi:“MI:0915”(physical association)	0.570
SMCO4	M6PR	psi-mi:“MI:0915”(physical association)	0.560
M6PR	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
M6PR	NINJ2	psi-mi:“MI:0915”(physical association)	0.560
M6PR	DUSP12	psi-mi:“MI:0915”(physical association)	0.560
M6PR	GIMAP5	psi-mi:“MI:0915”(physical association)	0.560
M6PR	KTN1	psi-mi:“MI:0915”(physical association)	0.560
M6PR	COMT	psi-mi:“MI:0915”(physical association)	0.560
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
HFE	ADAM10	psi-mi:“MI:0914”(association)	0.530
SCGB2A1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
HSPA12A	M6PR	psi-mi:“MI:0915”(physical association)	0.370
M6PR	GGA1	psi-mi:“MI:0915”(physical association)	0.370
TAFA1	M6PR	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350
NCAPD3	NDUFS8	psi-mi:“MI:0914”(association)	0.350
	VPS37C	psi-mi:“MI:0914”(association)	0.350
FGFR1	NDUFA4	psi-mi:“MI:0914”(association)	0.350
FGFR2	LANCL1	psi-mi:“MI:0914”(association)	0.350
NTRK3	ILVBL	psi-mi:“MI:0914”(association)	0.350
TYRO3	HAX1	psi-mi:“MI:0914”(association)	0.350
ARL3	TRAPPC13	psi-mi:“MI:0914”(association)	0.350

BioGRID (100): M6PR (Affinity Capture-RNA), M6PR (Affinity Capture-RNA), M6PR (Affinity Capture-RNA), M6PR (Affinity Capture-MS), M6PR (Affinity Capture-MS), M6PR (Affinity Capture-MS), M6PR (Affinity Capture-MS), M6PR (Affinity Capture-MS), M6PR (Affinity Capture-MS), M6PR (Co-fractionation), SYNJ2BP (Co-fractionation), TOMM22 (Co-fractionation), HSPA12A (Two-hybrid), DUSP12 (Two-hybrid), KTN1 (Two-hybrid)

ESM2 similar proteins: A1Z623, A3KFX0, A8YXY3, F1LQY6, O60613, P01137, P07200, P09533, P11456, P20645, P24668, P50747, P54831, Q08BI9, Q0IIH8, Q1LVW0, Q1LZ96, Q2KIJ6, Q2TBX5, Q3UHE1, Q3UX43, Q58E26, Q5C9Z4, Q5R812, Q5RB75, Q6AY20, Q6EDY6, Q6PCX7, Q6X4M2, Q802F3, Q802G7, Q80YV4, Q8BJQ9, Q8IVD9, Q8N6S4, Q8NC56, Q8R1N4, Q8R1T1, Q8TDX6, Q8VHC3

Diamond homologs: O59745, P11456, P20645, P24668, Q6AY20

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
“LE-TGN SNARE”	“up-regulates activity”	M6PR	relocalization
GCC2	“up-regulates activity”	M6PR	relocalization
RABEPK	“up-regulates activity”	M6PR	relocalization
PLIN3	“up-regulates activity”	M6PR	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

34 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1311 predictions. Top by Δscore:

Variant	Effect	Δscore
12:8941841:C:A	donor_gain	1.0000
12:8942410:ACTT:A	donor_loss	1.0000
12:8942411:CTT:C	donor_loss	1.0000
12:8942414:A:AC	donor_gain	1.0000
12:8942415:C:CA	donor_gain	1.0000
12:8942415:CT:C	donor_gain	1.0000
12:8942415:CTG:C	donor_gain	1.0000
12:8942415:CTGCT:C	donor_gain	1.0000
12:8942538:CAAAC:C	acceptor_gain	1.0000
12:8942539:AAAC:A	acceptor_gain	1.0000
12:8942540:AAC:A	acceptor_gain	1.0000
12:8942541:AC:A	acceptor_gain	1.0000
12:8942541:ACCT:A	acceptor_loss	1.0000
12:8942542:CC:C	acceptor_gain	1.0000
12:8942543:C:CC	acceptor_gain	1.0000
12:8942544:T:A	acceptor_loss	1.0000
12:8943403:A:AC	donor_gain	1.0000
12:8943404:C:CC	donor_gain	1.0000
12:8943799:A:AC	donor_gain	1.0000
12:8943800:C:CC	donor_gain	1.0000
12:8943800:CCG:C	donor_gain	1.0000
12:8945416:A:AC	donor_gain	1.0000
12:8945417:C:CC	donor_gain	1.0000
12:8945417:CTT:C	donor_gain	1.0000
12:8945419:T:TA	donor_gain	1.0000
12:8945580:CAAAG:C	acceptor_gain	1.0000
12:8945581:AAAG:A	acceptor_gain	1.0000
12:8945582:AAG:A	acceptor_gain	1.0000
12:8945584:GC:G	acceptor_loss	1.0000
12:8945585:C:CC	acceptor_gain	1.0000

AlphaMissense

1811 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:8942442:A:G	W229R	0.997
12:8942442:A:T	W229R	0.997
12:8941934:A:G	C240R	0.995
12:8942492:C:G	R212P	0.994
12:8943895:A:G	L120P	0.994
12:8941936:C:T	G239D	0.993
12:8943464:G:C	S175R	0.992
12:8943464:G:T	S175R	0.992
12:8943466:T:G	S175R	0.992
12:8943839:C:G	A139P	0.992
12:8945492:A:G	L90P	0.992
12:8941828:A:G	L275S	0.990
12:8941922:A:G	C244R	0.990
12:8941924:A:T	V243D	0.990
12:8942423:A:G	L235P	0.990
12:8942429:C:T	G233D	0.990
12:8942499:A:C	Y210D	0.990
12:8945529:A:G	C78R	0.990
12:8941937:C:G	G239R	0.989
12:8942418:C:G	A237P	0.988
12:8943488:A:C	C167W	0.988
12:8941841:C:G	D271H	0.987
12:8945450:C:T	G104E	0.987
12:8941919:G:T	R245S	0.986
12:8942478:C:G	A217P	0.986
12:8943490:A:G	C167R	0.986
12:8943820:C:T	C145Y	0.986
12:8945528:C:G	C78S	0.986
12:8945529:A:T	C78S	0.986
12:8942507:C:T	G207E	0.985

dbSNP variants (sampled 300 via entrez): RS1000586739 (12:8942275 G>A), RS1000783212 (12:8949874 A>G), RS1000813117 (12:8943041 C>G), RS1001110889 (12:8949595 G>A), RS1001843657 (12:8942971 T>A,C), RS1002019732 (12:8949787 T>C), RS1002070633 (12:8950009 G>A), RS1002534049 (12:8946083 T>G), RS1002754851 (12:8946949 A>G), RS1003133522 (12:8946651 T>C), RS1003509580 (12:8951386 T>C), RS1003766020 (12:8951381 A>C), RS1003887550 (12:8950481 A>G), RS1003945350 (12:8943837 T>C,G), RS1004163199 (12:8945227 A>G)

Disease associations

OMIM: gene MIM:154540 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004062_1	Sjögren’s syndrome	6.000000e-07
GCST006614_101	Total cholesterol levels	4.000000e-11
GCST90013445_5	Type 1 diabetes	4.000000e-08
GCST90013445_65	Type 1 diabetes	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5788 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression, increases expression	3
Acetaminophen	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
bisphenol A	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	increases phosphorylation	1
yessotoxin	increases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects expression, affects reaction	1
CGP 52608	increases reaction, affects binding	1
torcetrapib	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Chloroquine	affects localization	1
Cisplatin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Fluorouracil	increases expression	1
Gallic Acid	increases expression	1
Ivermectin	decreases expression	1
Ketoconazole	decreases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tretinoin	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL942205	Binding	Binding affinity to CI-M6PR	Synthesis of new sulfonate and phosphonate derivatives for cation-independent mannose 6-phosphate receptor targeting. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3AG	Abcam HEK293T M6PR KO	Transformed cell line	Female
CVCL_D7GV	Ubigene HEK293T M6PR KO	Transformed cell line	Female
CVCL_E0GU	Ubigene HeLa M6PR KO	Cancer cell line	Female
CVCL_SW18	HAP1 M6PR (-) 1	Cancer cell line	Male
CVCL_SW19	HAP1 M6PR (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.