MMD2

Summary

MMD2 (monocyte to macrophage differentiation associated 2, HGNC:30133) is a protein-coding gene on chromosome 7p22.1, encoding Monocyte to macrophage differentiation factor 2 (Q8IY49).

This gene encodes a member of the PAQR (progestin and adipoQ receptor) family. Members of this family are evolutionarily conserved with significant sequence identity to bacterial hemolysin-like proteins and are defined by a set of seven transmembrane domains. The protein encoded by this gene localizes to the Golgi apparatus to modulate Ras signaling. Alternative splicing results in multiple transcript variants and protein isoforms.

Source: NCBI Gene 221938 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_198403

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30133
Approved symbol	MMD2
Name	monocyte to macrophage differentiation associated 2
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	PAQR10
Ensembl gene	ENSG00000136297
Ensembl biotype	protein_coding
OMIM	614581
Entrez	221938

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000401401, ENST00000404774, ENST00000406755, ENST00000963657

RefSeq mRNA: 3 — MANE Select: NM_198403 NM_001100600, NM_001270375, NM_198403

CCDS: CCDS47529, CCDS47530, CCDS59047

Canonical transcript exons

ENST00000401401 — 7 exons

Exon	Start	End
ENSE00000923856	4920171	4920331
ENSE00000976404	4911145	4911246
ENSE00001307374	4925451	4925532
ENSE00001562968	4909881	4909950
ENSE00001706338	4916005	4916079
ENSE00001831476	4905998	4907599
ENSE00003907090	4958971	4959187

Expression profiles

Bgee: expression breadth broad, 85 present calls, max score 87.44.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6523 / max 40.2491, expressed in 107 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82556	0.6523	107

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	87.44	gold quality
spinal cord	UBERON:0002240	86.71	gold quality
nucleus accumbens	UBERON:0001882	85.17	gold quality
caudate nucleus	UBERON:0001873	85.11	gold quality
putamen	UBERON:0001874	84.92	gold quality
amygdala	UBERON:0001876	83.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.32	gold quality
anterior cingulate cortex	UBERON:0009835	80.99	gold quality
endothelial cell	CL:0000115	80.96	gold quality
substantia nigra	UBERON:0002038	79.87	gold quality
hypothalamus	UBERON:0001898	79.48	gold quality
midbrain	UBERON:0001891	78.97	gold quality
prefrontal cortex	UBERON:0000451	78.87	gold quality
pancreatic ductal cell	CL:0002079	78.77	silver quality
right frontal lobe	UBERON:0002810	78.77	gold quality
temporal lobe	UBERON:0001871	78.34	gold quality
tibialis anterior	UBERON:0001385	77.80	silver quality
forebrain	UBERON:0001890	77.23	gold quality
neocortex	UBERON:0001950	77.02	gold quality
buccal mucosa cell	CL:0002336	76.85	gold quality
frontal cortex	UBERON:0001870	76.59	gold quality
Ammon’s horn	UBERON:0001954	76.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.07	gold quality
cerebral cortex	UBERON:0000956	76.01	gold quality
brain	UBERON:0000955	75.83	gold quality
primary visual cortex	UBERON:0002436	75.79	gold quality
upper arm skin	UBERON:0004263	75.37	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.88	gold quality
ventricular zone	UBERON:0003053	74.69	gold quality
occipital lobe	UBERON:0002021	73.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting MMD2, 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-4425	100.00	67.59	1049
HSA-MIR-6870-5P	99.99	68.55	2115
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-185-3P	99.95	67.01	1743
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-3064-5P	99.26	66.13	1497

Literature-anchored findings (GeneRIF, showing 2)

• Collectively, this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQR11. (PMID:21968647)
• results of the present study indicate that Golgi localization is indispensable for PAQR10 to implement its regulatory functions in the Ras signalling cascade (PMID:22339580)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mmd2a	ENSDARG00000087446
danio_rerio	mmd2b	ENSDARG00000089090
		ENSDARG00000108505
mus_musculus	Mmd2	ENSMUSG00000039533
rattus_norvegicus	Mmd2	ENSRNOG00000001113
drosophila_melanogaster	AdipoR	FBGN0038984
caenorhabditis_elegans		WBGENE00016610
caenorhabditis_elegans		WBGENE00019643

Paralogs (10): ADIPOR2 (ENSG00000006831), MMD (ENSG00000108960), PAQR5 (ENSG00000137819), ADIPOR1 (ENSG00000159346), PAQR6 (ENSG00000160781), PAQR4 (ENSG00000162073), PAQR3 (ENSG00000163291), PAQR8 (ENSG00000170915), PAQR7 (ENSG00000182749), PAQR9 (ENSG00000188582)

Protein

Protein identifiers

Monocyte to macrophage differentiation factor 2 — Q8IY49 (reviewed: Q8IY49)

Alternative names: Progestin and adipoQ receptor family member 10, Progestin and adipoQ receptor family member X

All UniProt accessions (1): Q8IY49

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Shows restricted expression with highest levels in brain and testis.

Similarity. Belongs to the ADIPOR family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IY49-1	1	yes
Q8IY49-2	2
Q8IY49-3	3

RefSeq proteins (3): NP_001094070, NP_001257304, NP_940685* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004254	AdipoR/HlyIII-related	Family

Pfam: PF03006

UniProt features (21 total): topological domain 8, transmembrane region 7, sequence conflict 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IY49-F1	87.62	0.62

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 93 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEUROGENESIS, chr7p22, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, ACCAATC_MIR509, JOHANSSON_BRAIN_CANCER_EARLY_VS_LATE_DN, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS

GO Biological Process (4): regulation of protein localization (GO:0032880), positive regulation of neuron differentiation (GO:0045666), positive regulation of protein kinase activity (GO:0045860), positive regulation of Ras protein signal transduction (GO:0046579)

GO Molecular Function (3): protein kinase activity (GO:0004672), protein binding (GO:0005515), pore-forming activity (GO:0140911)

GO Cellular Component (4): Golgi membrane (GO:0000139), perinuclear region of cytoplasm (GO:0048471), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	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
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
molecular_function	1
Golgi apparatus	1
bounding membrane of organelle	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MMD2	DYSF	O75923	854
MMD2	ANO5	Q75V66	853
MMD2	PAQR3	Q6TCH7	634
MMD2	ADD2	P35612	493
MMD2	F10	P00742	492
MMD2	ZNF358	Q9NW07	447
MMD2	PAQR8	Q8TEZ7	439
MMD2	PAQR7	Q86WK9	397
MMD2	PAQR5	Q9NXK6	392
MMD2	ZCCHC24	Q8N2G6	389
MMD2	PAQR4	Q8N4S7	385
MMD2	ADIPOQ	Q15848	373
MMD2	LY96	Q9Y6Y9	355
MMD2	PAQR9	Q6ZVX9	354
MMD2	ZPLD1	Q8TCW7	346

IntAct

1 interactions, top by confidence:

BioGRID (8): MMD2 (Two-hybrid), MMD2 (Two-hybrid), MMD2 (Two-hybrid), TMEM14B (Two-hybrid), CREB3L1 (Two-hybrid), ASGR2 (Two-hybrid), SSMEM1 (Two-hybrid), SGPL1 (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: P67153, P67154, P67155, P67156, Q15546, Q719N3, Q8IY49, Q8R189, Q9CQY7, P54176

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1874 predictions. Top by Δscore:

Variant	Effect	Δscore
7:4907595:TTGGG:T	acceptor_gain	1.0000
7:4907596:TGGG:T	acceptor_gain	1.0000
7:4907598:GG:G	acceptor_gain	1.0000
7:4907600:C:CC	acceptor_gain	1.0000
7:4907605:G:T	acceptor_gain	1.0000
7:4911143:A:AC	donor_gain	1.0000
7:4911144:C:CC	donor_gain	1.0000
7:4911144:CCG:C	donor_gain	1.0000
7:4915997:GTACT:G	donor_loss	1.0000
7:4915999:ACT:A	donor_loss	1.0000
7:4916000:CTCA:C	donor_loss	1.0000
7:4916001:TCA:T	donor_loss	1.0000
7:4916002:CA:C	donor_loss	1.0000
7:4916003:A:AC	donor_gain	1.0000
7:4916003:AC:A	donor_gain	1.0000
7:4916004:C:CC	donor_gain	1.0000
7:4916004:C:CT	donor_loss	1.0000
7:4916004:CC:C	donor_gain	1.0000
7:4925450:CAG:C	donor_gain	1.0000
7:4958967:TCACC:T	donor_loss	1.0000
7:4958968:CA:C	donor_loss	1.0000
7:4958969:ACCTC:A	donor_loss	1.0000
7:4958970:CCTCG:C	donor_gain	1.0000
7:4907597:GGG:G	acceptor_gain	0.9900
7:4907597:GGGC:G	acceptor_loss	0.9900
7:4907600:C:CA	acceptor_loss	0.9900
7:4907607:C:CT	acceptor_gain	0.9900
7:4907608:A:T	acceptor_gain	0.9900
7:4909874:CACTT:C	donor_loss	0.9900
7:4909875:ACTTA:A	donor_loss	0.9900

AlphaMissense

1633 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:4907472:C:T	G246D	0.999
7:4907491:G:C	H240D	0.999
7:4907494:A:G	W239R	0.999
7:4907494:A:T	W239R	0.999
7:4916050:T:A	D107V	0.999
7:4916050:T:G	D107A	0.999
7:4920202:G:C	H87D	0.999
7:4920314:G:C	S49R	0.999
7:4920314:G:T	S49R	0.999
7:4920316:T:G	S49R	0.999
7:4925470:G:T	A37D	0.999
7:4907489:A:C	H240Q	0.998
7:4907489:A:T	H240Q	0.998
7:4907490:T:C	H240R	0.998
7:4907491:G:T	H240N	0.998
7:4907501:G:C	H236Q	0.998
7:4907501:G:T	H236Q	0.998
7:4907503:G:C	H236D	0.998
7:4907544:C:T	G222D	0.998
7:4907545:C:G	G222R	0.998
7:4911194:A:G	W140R	0.998
7:4911194:A:T	W140R	0.998
7:4911244:A:G	L123P	0.998
7:4916006:A:G	W122R	0.998
7:4916006:A:T	W122R	0.998
7:4916047:C:G	R108P	0.998
7:4920203:A:C	F86L	0.998
7:4920203:A:T	F86L	0.998
7:4920205:A:G	F86L	0.998
7:4920221:G:C	F80L	0.998

dbSNP variants (sampled 300 via entrez): RS1000022450 (7:4924589 C>T), RS1000092962 (7:4935297 A>C,G), RS1000097617 (7:4955490 T>G), RS1000212583 (7:4901231 A>G), RS1000226400 (7:4961040 G>A), RS1000251171 (7:4896058 G>A,C), RS1000274279 (7:4926839 G>A), RS1000278505 (7:4926738 CTTT>C,CTT,CTTTT), RS1000370164 (7:4935728 G>C), RS1000382893 (7:4932337 G>A), RS1000412399 (7:4932606 C>T), RS1000424361 (7:4900805 C>G,T), RS1000480419 (7:4930824 C>T), RS1000492177 (7:4898770 G>A,C,T), RS1000533100 (7:4955272 T>C)

Disease associations

OMIM: gene MIM:614581 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): megacolon (MONDO:0001273)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008531	Megacolon	C06.405.469.158.701

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ethyl-p-hydroxybenzoate	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04340856	Not specified	COMPLETED	Retrospective, Uncontrolled Cohort Study on the Therapy of Chronic Megalon
NCT07470892	Not specified	NOT_YET_RECRUITING	Preoperative Fish Oil PN and Prognosis After Constipation Surgery