MREG

Summary

MREG (melanoregulin, HGNC:25478) is a protein-coding gene on chromosome 2q35, encoding Melanoregulin (Q8N565). Probably functions as a cargo-recognition protein that couples cytoplasmic vesicles to the transport machinery.

Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in melanocyte differentiation; melanosome transport; and phagosome maturation. Predicted to act upstream of or within developmental pigmentation. Predicted to be located in late endosome membrane and melanosome membrane. Predicted to be part of protein-containing complex. Predicted to be active in melanosome.

Source: NCBI Gene 55686 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_018000

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25478
Approved symbol	MREG
Name	melanoregulin
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10116, DSU, WDT2
Ensembl gene	ENSG00000118242
Ensembl biotype	protein_coding
OMIM	609207
Entrez	55686

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000263268, ENST00000420348, ENST00000424992, ENST00000439791

RefSeq mRNA: 4 — MANE Select: NM_018000 NM_001372188, NM_001372189, NM_001372190, NM_018000

CCDS: CCDS46513

Canonical transcript exons

ENST00000263268 — 5 exons

Exon	Start	End
ENSE00000785523	215947023	215947113
ENSE00000796823	215945571	215945734
ENSE00001215720	215942584	215944997
ENSE00001215729	216013233	216013551
ENSE00003518750	215996306	215996465

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 96.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.2067 / max 387.0129, expressed in 1408 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33759	15.6864	1060
33760	3.5203	1090

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	96.95	gold quality
esophagus squamous epithelium	UBERON:0006920	94.96	gold quality
gingival epithelium	UBERON:0001949	94.47	gold quality
squamous epithelium	UBERON:0006914	94.25	gold quality
epithelium of esophagus	UBERON:0001976	93.93	gold quality
gingiva	UBERON:0001828	93.86	gold quality
oral cavity	UBERON:0000167	93.45	gold quality
cervix epithelium	UBERON:0004801	92.69	gold quality
cervix squamous epithelium	UBERON:0006922	92.66	silver quality
lower esophagus mucosa	UBERON:0035834	92.59	gold quality
palpebral conjunctiva	UBERON:0001812	92.24	gold quality
epithelium of nasopharynx	UBERON:0001951	90.48	gold quality
cerebellar vermis	UBERON:0004720	90.16	gold quality
cerebellar cortex	UBERON:0002129	90.13	gold quality
cerebellum	UBERON:0002037	90.12	gold quality
cerebellar hemisphere	UBERON:0002245	90.11	gold quality
upper leg skin	UBERON:0004262	89.72	gold quality
mammalian vulva	UBERON:0000997	89.54	gold quality
oviduct epithelium	UBERON:0004804	89.33	gold quality
esophagus mucosa	UBERON:0002469	89.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.05	gold quality
pigmented layer of retina	UBERON:0001782	88.59	gold quality
retina	UBERON:0000966	88.57	gold quality
epithelium of mammary gland	UBERON:0003244	87.97	gold quality
skin of hip	UBERON:0001554	87.96	gold quality
mammary duct	UBERON:0001765	87.83	gold quality
tongue squamous epithelium	UBERON:0006919	87.78	gold quality
penis	UBERON:0000989	86.28	gold quality
right lobe of liver	UBERON:0001114	85.51	gold quality
zone of skin	UBERON:0000014	85.11	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

90 targeting MREG, 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-4425	100.00	67.59	1049
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833

Literature-anchored findings (GeneRIF, showing 2)

• MREG-dependent processing links both autophagic and phagocytic processes in LC3-associated phagocytosis. MREG participates in coordinating the association of phagosomes with LC3 for content degradation with the MREG loss leading to phagosome accumulation. (PMID:25301234)
• Taken together, MREG regulates thyroid cancer cell invasion and proliferation through PI3K/Akt-mTOR signaling pathway. MREG may serve as a promising therapeutic strategy for thyroid cancer. (PMID:28698135)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mreg	ENSMUSG00000039395
rattus_norvegicus	Mreg	ENSRNOG00000015774

Protein

Protein identifiers

Melanoregulin — Q8N565 (reviewed: Q8N565)

Alternative names: Dilute suppressor protein homolog

All UniProt accessions (4): Q8N565, C9JAG4, C9JFU1, C9JYV9

UniProt curated annotations — full annotation on UniProt →

Function. Probably functions as a cargo-recognition protein that couples cytoplasmic vesicles to the transport machinery. Plays a role in hair pigmentation, a process that involves shedding of melanosome-containing vesicles from melanocytes, followed by phagocytosis of the melanosome-containing vesicles by keratinocytes. Functions on melanosomes as receptor for RILP and the complex formed by RILP and DCTN1, and thereby contributes to retrograde melanosome transport from the cell periphery to the center. Overexpression causes accumulation of late endosomes and/or lysosomes at the microtubule organising center (MTOC) at the center of the cell. Probably binds cholesterol and requires the presence of cholesterol in membranes to function in microtubule-mediated retrograde organelle transport. Binds phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate and phosphatidylinositol 3,5-bisphosphate, but not phosphatidylinositol 3,4-bisphosphate or phosphatidylinositol 4,5-bisphosphate. Required for normal phagosome clearing and normal activation of lysosomal enzymes in lysosomes from retinal pigment epithelium cells. Required for normal degradation of the lipofuscin component N-retinylidene-N-retinylethanolamine (A2E) in the eye. May function in membrane fusion and regulate the biogenesis of disk membranes of photoreceptor rod cells.

Subunit / interactions. Identified in a complex with RILP and DCTN1; interacts directly with RILP, but does not interact directly with DCTN1. Interacts with PRPH2.

Subcellular location. Apical cell membrane. Melanosome membrane. Lysosome membrane. Cytoplasmic vesicle membrane.

Tissue specificity. Expressed in photoreceptor cells (at protein level).

Post-translational modifications. Palmitoylated. Palmitoylation is required to maintain the protein at the melanosome membrane.

Similarity. Belongs to the melanoregulin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N565-1	1	yes
Q8N565-2	2

RefSeq proteins (4): NP_001359117, NP_001359118, NP_001359119, NP_060470* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031638	Melanoregulin	Family

Pfam: PF15812

UniProt features (7 total): sequence conflict 2, chain 1, short sequence motif 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N565-F1	72.97	0.38

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): 213

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 218 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, RRAGTTGT_UNKNOWN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_PIGMENT_GRANULE_LOCALIZATION, GOBP_VESICLE_LOCALIZATION, MODULE_255, GOCC_VACUOLAR_MEMBRANE, MODULE_418, MODULE_317, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_CELLULAR_PIGMENTATION, TGACCTY_ERR1_Q2, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, CEBPB_01

GO Biological Process (7): melanocyte differentiation (GO:0030318), melanosome localization (GO:0032400), melanosome transport (GO:0032402), minus-end-directed organelle transport along microtubule (GO:0072385), phagosome maturation (GO:0090382), pigmentation (GO:0043473), developmental pigmentation (GO:0048066)

GO Molecular Function (3): phosphatidylinositol binding (GO:0035091), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (12): lysosomal membrane (GO:0005765), apical plasma membrane (GO:0016324), cytoplasmic vesicle membrane (GO:0030659), organelle membrane (GO:0031090), late endosome membrane (GO:0031902), protein-containing complex (GO:0032991), melanosome membrane (GO:0033162), melanosome (GO:0042470), lysosome (GO:0005764), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
membrane	2
pigment cell differentiation	1
pigment granule localization	1
melanosome localization	1
establishment of melanosome localization	1
pigment granule transport	1
organelle transport along microtubule	1
phagolysosome assembly	1
exocytosis	1
organelle organization	1
biological_process	1
pigmentation	1
anion binding	1
lysosome	1
lytic vacuole membrane	1
apical part of cell	1
plasma membrane region	1
vesicle membrane	1
cytoplasmic vesicle	1
membrane-bounded organelle	1
late endosome	1
endosome membrane	1
cellular_component	1
melanosome	1
chitosome	1
pigment granule membrane	1
pigment granule	1
lytic vacuole	1
cell periphery	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

502 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MREG	MYO5A	Q9Y4I1	887
MREG	RAB27A	P51159	827
MREG	MLPH	Q9BV36	807
MREG	RAB27B	O00194	690
MREG	RILP	Q96NA2	587
MREG	DCTN1	Q14203	518
MREG	KPNA6	O60684	450
MREG	MAP1S	Q66K74	446
MREG	MAP1A	P78559	445
MREG	B4E171	B4E171	437
MREG	MAP1B	P46821	435
MREG	CHML	P26374	424
MREG	DCAF17	Q5H9S7	419
MREG	RAB36	O95755	418
MREG	MAP1LC3B	Q9GZQ8	414

IntAct

11 interactions, top by confidence:

A	B	Type	Score
MREG	EIF1AD	psi-mi:“MI:0915”(physical association)	0.560
MREG	CFTR	psi-mi:“MI:0915”(physical association)	0.370
Cdc26		psi-mi:“MI:0914”(association)	0.350
Naa10	MYO9A	psi-mi:“MI:0914”(association)	0.350
PTPN1		psi-mi:“MI:0914”(association)	0.350
TOR1AIP1	USP1	psi-mi:“MI:0914”(association)	0.350
MREG	SPAG9	psi-mi:“MI:0914”(association)	0.350
SLC2A8	AP3D1	psi-mi:“MI:0914”(association)	0.350
EIF1AD	MREG	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): HSP90AB4P (Affinity Capture-MS), SPAG9 (Affinity Capture-MS), WDR44 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), UBA5 (Affinity Capture-MS), BHMT (Affinity Capture-MS), MREG (Affinity Capture-MS), MREG (Affinity Capture-MS), MREG (Affinity Capture-MS), MREG (Affinity Capture-MS), SPAG9 (Affinity Capture-MS), UBA5 (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), MREG (Affinity Capture-RNA)

ESM2 similar proteins: A0A0F7YYX3, A1IGX5, A4UZ23, A6H7E2, A6NKT7, A9ULR1, B6DDZ5, E1BRC3, O14715, O57571, O76061, O88452, O97561, P01580, P01581, P04823, P28341, P46402, Q15846, Q17F11, Q3ZRW6, Q3ZRW7, Q3ZRW9, Q499E0, Q5CCK0, Q5E9H1, Q5I0J4, Q5JX71, Q5K6N0, Q5RAT2, Q5RBH2, Q5RDR5, Q5U2T4, Q6AYF7, Q6DFY8, Q6NVG5, Q76B58, Q8IR45, Q8K1M7, Q8K1M8

Diamond homologs: Q0P4L7, Q6GQM0, Q6NVG5, Q8N565

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1250 predictions. Top by Δscore:

Variant	Effect	Δscore
2:215944993:CGGTC:C	acceptor_gain	1.0000
2:215944996:TC:T	acceptor_gain	1.0000
2:215944997:CC:C	acceptor_gain	1.0000
2:215944998:C:CC	acceptor_gain	1.0000
2:215944998:CTG:C	acceptor_loss	1.0000
2:215944999:T:A	acceptor_loss	1.0000
2:215945566:CTTA:C	donor_loss	1.0000
2:215945567:TTACC:T	donor_loss	1.0000
2:215945568:TA:T	donor_loss	1.0000
2:215945569:A:AC	donor_gain	1.0000
2:215945569:AC:A	donor_gain	1.0000
2:215945569:ACCAC:A	donor_loss	1.0000
2:215945570:C:CC	donor_gain	1.0000
2:215945570:CC:C	donor_gain	1.0000
2:215945570:CCA:C	donor_gain	1.0000
2:215945570:CCACA:C	donor_gain	1.0000
2:215945734:CCTAA:C	acceptor_loss	1.0000
2:215945735:C:G	acceptor_loss	1.0000
2:215947018:CTTA:C	donor_loss	1.0000
2:215947019:TTAC:T	donor_loss	1.0000
2:215947021:A:AC	donor_gain	1.0000
2:215947022:C:CA	donor_loss	1.0000
2:215947022:C:CC	donor_gain	1.0000
2:215947022:CCTAA:C	donor_gain	1.0000
2:215947109:CACTC:C	acceptor_gain	1.0000
2:215947110:ACTC:A	acceptor_gain	1.0000
2:215947111:CTC:C	acceptor_gain	1.0000
2:215947111:CTCC:C	acceptor_gain	1.0000
2:215947112:TC:T	acceptor_gain	1.0000
2:215947112:TCCT:T	acceptor_gain	1.0000

AlphaMissense

1403 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:215947047:A:G	W108R	0.997
2:215947047:A:T	W108R	0.997
2:215945730:A:C	F117L	0.995
2:215945730:A:T	F117L	0.995
2:215945731:A:G	F117S	0.995
2:215945732:A:G	F117L	0.995
2:215947046:C:G	W108S	0.993
2:215947045:C:A	W108C	0.992
2:215947045:C:G	W108C	0.992
2:215947034:A:G	L112S	0.991
2:215944962:G:C	F182L	0.990
2:215944962:G:T	F182L	0.990
2:215944964:A:G	F182L	0.990
2:215944990:A:T	L173H	0.990
2:215944951:G:T	A186D	0.989
2:215944990:A:G	L173P	0.989
2:215945613:G:C	F156L	0.988
2:215945613:G:T	F156L	0.988
2:215945615:A:G	F156L	0.988
2:215945614:A:G	F156S	0.987
2:215944993:C:G	R172P	0.985
2:215945575:A:T	V169D	0.985
2:215996404:A:G	W53R	0.985
2:215996404:A:T	W53R	0.985
2:215945614:A:C	F156C	0.983
2:215945707:A:G	L125S	0.983
2:215945710:A:G	L124S	0.982
2:215945623:G:A	T153I	0.981
2:215996402:C:A	W53C	0.981
2:215996402:C:G	W53C	0.981

dbSNP variants (sampled 300 via entrez): RS1000021477 (2:215978360 C>A,T), RS1000063399 (2:215989545 T>C,G), RS1000090596 (2:215994066 A>G), RS1000125091 (2:215951671 C>A), RS1000147512 (2:215972198 C>T), RS1000153308 (2:215942112 C>T), RS1000173620 (2:215969777 G>C), RS1000180797 (2:216012039 C>T), RS1000182425 (2:216010994 G>A), RS1000228731 (2:216024202 C>T), RS1000255022 (2:215942643 A>G), RS1000258487 (2:216005217 G>A), RS1000291398 (2:216005566 C>T), RS1000324153 (2:216005581 A>G), RS1000390655 (2:215978054 A>T)

Disease associations

OMIM: gene MIM:609207 | 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
GCST002039_3	Blood trace element (Se levels)	3.000000e-06
GCST006976_67	Macular thickness	5.000000e-10
GCST010479_62	Coronary artery disease	2.000000e-14
GCST012322_47	Triglyceride levels x SSRI defined daily dose interaction in schizophrenia or bipolar disorder	4.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0005658	response to selective serotonin reuptake inhibitor

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, increases methylation, affects expression	4
Estradiol	increases expression, increases reaction, affects expression	3
Valproic Acid	affects expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	2
FR900359	decreases phosphorylation	1
bisphenol A	increases methylation	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
afimoxifene	decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
gardiquimod	increases expression, decreases reaction	1
MT19c compound	increases expression	1
Zoledronic Acid	increases expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1
Demecolcine	increases expression	1
Estrogens	decreases reaction, increases expression	1
Lipopolysaccharides	decreases reaction, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

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