MMD

Summary

MMD (monocyte to macrophage differentiation associated, HGNC:7153) is a protein-coding gene on chromosome 17q22, encoding Monocyte to macrophage differentiation factor (Q15546). Involved in the dynamics of lysosomal membranes associated with microglial activation following brain lesion.

This protein is expressed by in vitro differentiated macrophages but not freshly isolated monocytes. Although sequence analysis identifies seven potential transmembrane domains, this protein has little homology to G-protein receptors and it has not been positively identified as a receptor. A suggested alternative function is that of an ion channel protein in maturing macrophages.

Source: NCBI Gene 23531 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_012329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7153
Approved symbol	MMD
Name	monocyte to macrophage differentiation associated
Location	17q22
Locus type	gene with protein product
Status	Approved
Aliases	MMA, PAQR11
Ensembl gene	ENSG00000108960
Ensembl biotype	protein_coding
OMIM	604467
Entrez	23531

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000262065, ENST00000571578, ENST00000577038, ENST00000649377, ENST00000936217, ENST00000936218

RefSeq mRNA: 1 — MANE Select: NM_012329 NM_012329

CCDS: CCDS11586

Canonical transcript exons

ENST00000262065 — 7 exons

Exon	Start	End
ENSE00000738584	55411257	55411417
ENSE00000820157	55414151	55414232
ENSE00001101592	55392622	55394534
ENSE00001101609	55403767	55403868
ENSE00001790143	55407746	55407820
ENSE00003791012	55401469	55401538
ENSE00003838127	55421670	55421835

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7142 / max 485.2808, expressed in 1527 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167078	4.9961	1276
167077	4.2949	874
167079	1.2166	692
167076	0.2066	65

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	97.80	gold quality
endothelial cell	CL:0000115	97.79	gold quality
orbitofrontal cortex	UBERON:0004167	97.60	gold quality
monocyte	CL:0000576	97.48	gold quality
CA1 field of hippocampus	UBERON:0003881	97.45	gold quality
mononuclear cell	CL:0000842	97.34	gold quality
amygdala	UBERON:0001876	97.26	gold quality
Ammon’s horn	UBERON:0001954	97.22	gold quality
putamen	UBERON:0001874	97.12	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.08	gold quality
temporal lobe	UBERON:0001871	96.78	gold quality
leukocyte	CL:0000738	96.69	gold quality
buccal mucosa cell	CL:0002336	96.36	gold quality
entorhinal cortex	UBERON:0002728	96.34	gold quality
caudate nucleus	UBERON:0001873	96.30	gold quality
medial globus pallidus	UBERON:0002477	96.23	gold quality
middle temporal gyrus	UBERON:0002771	96.09	gold quality
frontal pole	UBERON:0002795	96.03	gold quality
postcentral gyrus	UBERON:0002581	95.98	gold quality
superior frontal gyrus	UBERON:0002661	95.68	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.43	gold quality
cortical plate	UBERON:0005343	95.32	gold quality
cingulate cortex	UBERON:0003027	95.29	gold quality
telencephalon	UBERON:0001893	95.20	gold quality
anterior cingulate cortex	UBERON:0009835	95.20	gold quality
skin of hip	UBERON:0001554	95.18	gold quality
parietal lobe	UBERON:0001872	95.04	gold quality
globus pallidus	UBERON:0001875	95.04	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.93	gold quality
prefrontal cortex	UBERON:0000451	94.88	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	6.48
E-ANND-3	yes	5.97
E-GEOD-36552	no	36.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

218 targeting MMD, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960

Literature-anchored findings (GeneRIF, showing 6)

• this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQR11. (PMID:21968647)
• Together, our results highlight the significance of miR-140-5p/MMD axis in lung cancer, and miR-140-5p/MMD axis could serve as new molecular targets for the therapy against lung cancer. (PMID:24971538)
• high PAQR11 levels were correlated with epithelial-to-mesenchymal transition (EMT) and shorter survival in human cancers, and PAQR11 was found to be essential for tumor cell migration and metastasis in EMT-driven lung adenocarcinoma models. (PMID:27869652)
• Expression of PBX1 and MMD was higher in the second trimester among lupus patients who experienced a poor pregnancy outcome compared to those who did not. The pilot study identified two candidate genes that are reflective of the platelet function response to aspirin. (PMID:31684818)
• PAQR11 modulates monocyte-to-macrophage differentiation and pathogenesis of rheumatoid arthritis. (PMID:33421113)
• MMD collaborates with ACSL4 and MBOAT7 to promote polyunsaturated phosphatidylinositol remodeling and susceptibility to ferroptosis. (PMID:37691145)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmd	ENSDARG00000040387
mus_musculus	Mmd	ENSMUSG00000003948
rattus_norvegicus	Mmd	ENSRNOG00000002436
drosophila_melanogaster	AdipoR	FBGN0038984
caenorhabditis_elegans		WBGENE00016610
caenorhabditis_elegans		WBGENE00019643

Paralogs (10): ADIPOR2 (ENSG00000006831), MMD2 (ENSG00000136297), PAQR5 (ENSG00000137819), ADIPOR1 (ENSG00000159346), PAQR6 (ENSG00000160781), PAQR4 (ENSG00000162073), PAQR3 (ENSG00000163291), PAQR8 (ENSG00000170915), PAQR7 (ENSG00000182749), PAQR9 (ENSG00000188582)

Protein

Protein identifiers

Monocyte to macrophage differentiation factor — Q15546 (reviewed: Q15546)

Alternative names: Progestin and adipoQ receptor family member 11, Progestin and adipoQ receptor family member XI

All UniProt accessions (3): Q15546, A0A3B3ITQ3, I3L1Y1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the dynamics of lysosomal membranes associated with microglial activation following brain lesion.

Subcellular location. Late endosome membrane. Lysosome membrane.

Tissue specificity. Exhibits relatively ubiquitous expression with preferential expression in mature (in vitro differentiated) macrophages.

Similarity. Belongs to the ADIPOR family.

RefSeq proteins (1): NP_036461* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004254	AdipoR/HlyIII-related	Family
IPR005744	Hy-lIII	Family

Pfam: PF03006

UniProt features (18 total): topological domain 8, transmembrane region 7, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15546-F1	91.93	0.81

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 414 (showing top): MODULE_52, GOBP_REGULATION_OF_PHOSPHORYLATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_VACUOLAR_MEMBRANE, ATACCTC_MIR202, MODULE_45, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEUROGENESIS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

GO Biological Process (3): regulation of protein localization (GO:0032880), positive regulation of neuron differentiation (GO:0045666), positive regulation of protein kinase activity (GO:0045860)

GO Molecular Function (4): protein kinase activity (GO:0004672), signaling receptor activity (GO:0038023), pore-forming activity (GO:0140911), protein binding (GO:0005515)

GO Cellular Component (7): lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), late endosome membrane (GO:0031902), lysosome (GO:0005764), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
intracellular protein localization	1
regulation of localization	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
positive regulation of protein phosphorylation	1
protein kinase activity	1
positive regulation of kinase activity	1
regulation of protein kinase activity	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
molecular transducer activity	1
molecular_function	1
binding	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1
late endosome	1
endosome membrane	1
lytic vacuole	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMD	PAQR3	Q6TCH7	762
MMD	NXPE2	Q96DL1	504
MMD	PAQR4	Q8N4S7	481
MMD	PAQR8	Q8TEZ7	478
MMD	PAQR5	Q9NXK6	474
MMD	PAQR7	Q86WK9	444
MMD	HILPDA	Q9Y5L2	416
MMD	PAQR9	Q6ZVX9	400
MMD	CSF1R	P07333	395
MMD	ANKFN1	Q8N957	390
MMD	STARD13	Q9Y3M8	387
MMD	STXBP4	Q6ZWJ1	365
MMD	ADIPOR1	Q96A54	363
MMD	HMGB3	O15347	358
MMD	NCOA5	Q9HCD5	350

IntAct

58 interactions, top by confidence:

A	B	Type	Score
GAST	MMD	psi-mi:“MI:0915”(physical association)	0.560
MMD	GPX8	psi-mi:“MI:0915”(physical association)	0.560
MMD	OCIAD1	psi-mi:“MI:0915”(physical association)	0.560
MMD	GPR152	psi-mi:“MI:0915”(physical association)	0.560
MMD	PLEKHO1	psi-mi:“MI:0915”(physical association)	0.560
CYP4F2	MMD	psi-mi:“MI:0915”(physical association)	0.560
MMD	SELENOK	psi-mi:“MI:0915”(physical association)	0.560
MMD	TMEM42	psi-mi:“MI:0915”(physical association)	0.560
MMD	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
MS4A1	MMD	psi-mi:“MI:0915”(physical association)	0.560
MMD	SFXN1	psi-mi:“MI:0915”(physical association)	0.560
MMD	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
MMD	ARLN	psi-mi:“MI:0915”(physical association)	0.560
MMD	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
MMD	EMC6	psi-mi:“MI:0915”(physical association)	0.560
MMD	ATP13A1	psi-mi:“MI:0915”(physical association)	0.560
MMD	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
MMD	TMEM203	psi-mi:“MI:0915”(physical association)	0.560
MMD	YIPF6	psi-mi:“MI:0915”(physical association)	0.560
MMD	GPR152	psi-mi:“MI:0915”(physical association)	0.000
MMD	PLEKHO1	psi-mi:“MI:0915”(physical association)	0.000
CYP4F2	MMD	psi-mi:“MI:0915”(physical association)	0.000
SELENOK	MMD	psi-mi:“MI:0915”(physical association)	0.000
TMEM42	MMD	psi-mi:“MI:0915”(physical association)	0.000
AGTRAP	MMD	psi-mi:“MI:0915”(physical association)	0.000
MS4A1	MMD	psi-mi:“MI:0915”(physical association)	0.000
TMEM60	MMD	psi-mi:“MI:0915”(physical association)	0.000
ARLN	MMD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): MMD (Affinity Capture-RNA), MMD (Two-hybrid), MMD (Two-hybrid), OCIAD1 (Two-hybrid), SELK (Two-hybrid), FAM209A (Two-hybrid), EMC6 (Two-hybrid), TMEM60 (Two-hybrid), MS4A1 (Two-hybrid), C4orf3 (Two-hybrid), GPX8 (Two-hybrid), SFXN1 (Two-hybrid), ARL13B (Two-hybrid), TMEM42 (Two-hybrid), GPR152 (Two-hybrid)

ESM2 similar proteins: A0A1B0GVZ9, A4IFN5, A5PK40, A6NH52, A6NI61, B2LYG4, B2RZC9, B6ID01, D2HKB0, D3ZG27, P86229, Q0VDI3, Q15012, Q15546, Q17QJ2, Q1RLT2, Q2TA01, Q4R4I5, Q4R6E8, Q5H8A4, Q5R7Q1, Q5RAH0, Q5RL79, Q5U3C3, Q5VTY9, Q5ZML7, Q64232, Q6PHN7, Q6QRN8, Q719N3, Q71SV0, Q8BWB6, Q8IY49, Q8N6M3, Q8NFT2, Q8R189, Q8VD53, Q8VDI9, Q8VDR5, Q9CQC4

Diamond homologs: O51144, O84000, P54175, P54176, P67153, P67154, P67155, P67156, P67158, P9WFN6, P9WFN7, Q15546, Q719N3, Q8R189, Q9CQY7, Q8IY49

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1267 predictions. Top by Δscore:

Variant	Effect	Δscore
17:55394535:C:CC	acceptor_gain	1.0000
17:55394540:A:T	acceptor_gain	1.0000
17:55394542:C:CT	acceptor_gain	1.0000
17:55394543:A:T	acceptor_gain	1.0000
17:55401536:TAT:T	acceptor_gain	1.0000
17:55401536:TATC:T	acceptor_loss	1.0000
17:55401539:C:CC	acceptor_gain	1.0000
17:55401539:CT:C	acceptor_loss	1.0000
17:55403765:A:AC	donor_gain	1.0000
17:55403766:C:CC	donor_gain	1.0000
17:55411414:GGAA:G	acceptor_gain	1.0000
17:55411415:GAA:G	acceptor_gain	1.0000
17:55411416:AA:A	acceptor_gain	1.0000
17:55411416:AAC:A	acceptor_loss	1.0000
17:55411418:C:CC	acceptor_gain	1.0000
17:55411418:CTGA:C	acceptor_loss	1.0000
17:55411419:T:C	acceptor_loss	1.0000
17:55414145:AC:A	donor_loss	1.0000
17:55414146:CTCA:C	donor_gain	1.0000
17:55414147:TCACT:T	donor_loss	1.0000
17:55414148:CA:C	donor_loss	1.0000
17:55414149:A:AC	donor_gain	1.0000
17:55414149:AC:A	donor_loss	1.0000
17:55414149:ACTG:A	donor_gain	1.0000
17:55414150:C:A	donor_loss	1.0000
17:55414150:C:CT	donor_gain	1.0000
17:55414150:CT:C	donor_gain	1.0000
17:55414150:CTG:C	donor_gain	1.0000
17:55414150:CTGC:C	donor_gain	1.0000
17:55414150:CTGCG:C	donor_gain	1.0000

AlphaMissense

1570 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:55394426:G:C	H209D	0.999
17:55394429:A:G	W208R	0.999
17:55394429:A:T	W208R	0.999
17:55394436:G:C	H205Q	0.999
17:55394436:G:T	H205Q	0.999
17:55394438:G:C	H205D	0.999
17:55394480:C:G	G191R	0.999
17:55394480:C:T	G191R	0.999
17:55403816:A:G	W133R	0.999
17:55403816:A:T	W133R	0.999
17:55407747:A:G	W115R	0.999
17:55407747:A:T	W115R	0.999
17:55407791:T:A	D100V	0.999
17:55407791:T:G	D100A	0.999
17:55411289:A:C	F79L	0.999
17:55411289:A:T	F79L	0.999
17:55411291:A:G	F79L	0.999
17:55394424:G:C	H209Q	0.998
17:55394424:G:T	H209Q	0.998
17:55394425:T:C	H209R	0.998
17:55394426:G:T	H209N	0.998
17:55394427:C:A	W208C	0.998
17:55394427:C:G	W208C	0.998
17:55394455:C:A	G199V	0.998
17:55394466:G:C	F195L	0.998
17:55394466:G:T	F195L	0.998
17:55394467:A:G	F195S	0.998
17:55394468:A:G	F195L	0.998
17:55394479:C:T	G191E	0.998
17:55407762:C:G	A110P	0.998

dbSNP variants (sampled 300 via entrez): RS1000054124 (17:55401517 A>G), RS1000396547 (17:55414770 T>C), RS1000419712 (17:55407502 C>T), RS1000430907 (17:55421344 C>A), RS1000507294 (17:55421247 C>T), RS1000753622 (17:55408808 C>G), RS1000767588 (17:55420114 CA>C), RS1000772831 (17:55414698 C>A,G), RS1000839742 (17:55395789 C>T), RS1000953828 (17:55395374 G>C), RS1001149531 (17:55395853 G>A,T), RS1001156766 (17:55409178 T>C), RS1001232731 (17:55402017 G>A), RS1001280883 (17:55408682 G>T), RS1001415287 (17:55422004 G>A)

Disease associations

OMIM: gene MIM:604467 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_930	Obesity-related traits	3.000000e-06
GCST003542_23	Night sleep phenotypes	4.000000e-06
GCST006979_505	Heel bone mineral density	6.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression, affects cotreatment	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
(+)-JQ1 compound	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
mirdametinib	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Calcitriol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ellagic Acid	increases expression	1
Estradiol	decreases expression	1

Clinical trials (associated diseases)

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