MTMR3

Summary

MTMR3 (myotubularin related protein 3, HGNC:7451) is a protein-coding gene on chromosome 22q12.2, encoding Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR3 (Q13615). Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylinositol 5-phosphate.

This gene encodes a member of the myotubularin dual specificity protein phosphatase gene family. The encoded protein is structurally similar to myotubularin but in addition contains a FYVE domain and an N-terminal PH-GRAM domain. The protein can self-associate and also form heteromers with another myotubularin related protein. The protein binds to phosphoinositide lipids through the PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. The encoded protein has been observed to have a perinuclear, possibly membrane-bound, distribution in cells, but it has also been found free in the cytoplasm. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8897 — RefSeq curated summary.

At a glance

• GWAS associations: 33
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_021090

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7451
Approved symbol	MTMR3
Name	myotubularin related protein 3
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0371, ZFYVE10, FYVE-DSP1
Ensembl gene	ENSG00000100330
Ensembl biotype	protein_coding
OMIM	603558
Entrez	8897

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 19 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000323630, ENST00000333027, ENST00000351488, ENST00000401950, ENST00000406629, ENST00000415511, ENST00000445401, ENST00000480776, ENST00000487907, ENST00000491251, ENST00000492087, ENST00000495098, ENST00000908090, ENST00000908091, ENST00000908092, ENST00000908093, ENST00000908094, ENST00000908095, ENST00000908096, ENST00000908097, ENST00000940445, ENST00000956488, ENST00000956489, ENST00000956490, ENST00000956491

RefSeq mRNA: 3 — MANE Select: NM_021090 NM_021090, NM_153050, NM_153051

CCDS: CCDS13870, CCDS13871, CCDS46682

Canonical transcript exons

ENST00000401950 — 20 exons

Exon	Start	End
ENSE00000652157	30013356	30013541
ENSE00000652158	30016528	30016698
ENSE00000652159	30017927	30018072
ENSE00000652161	30022029	30022139
ENSE00000652162	30022609	30022697
ENSE00001170577	30012368	30012563
ENSE00001170587	30009018	30009129
ENSE00001170597	30007901	30008032
ENSE00001170616	30002880	30002993
ENSE00001170625	29998761	29998857
ENSE00001170789	29957036	29957088
ENSE00001170800	30019480	30020884
ENSE00001877889	29883174	29883359
ENSE00001938117	30025630	30030868
ENSE00003556346	30007114	30007319
ENSE00003575956	29991504	29991670
ENSE00003593834	29988480	29988562
ENSE00003605061	29978936	29979052
ENSE00003648363	29970976	29971062
ENSE00003669172	29978442	29978531

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6384 / max 862.7390, expressed in 1786 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191634	12.6384	1786

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.44	gold quality
secondary oocyte	CL:0000655	99.25	gold quality
blood	UBERON:0000178	94.29	gold quality
lower esophagus mucosa	UBERON:0035834	92.76	gold quality
bone marrow cell	CL:0002092	92.57	gold quality
right uterine tube	UBERON:0001302	92.20	gold quality
skin of leg	UBERON:0001511	91.85	gold quality
monocyte	CL:0000576	91.59	gold quality
sural nerve	UBERON:0015488	91.59	gold quality
mononuclear cell	CL:0000842	91.37	gold quality
leukocyte	CL:0000738	91.32	gold quality
calcaneal tendon	UBERON:0003701	91.20	gold quality
amniotic fluid	UBERON:0000173	91.13	gold quality
skin of abdomen	UBERON:0001416	90.90	gold quality
right lung	UBERON:0002167	90.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.49	gold quality
bone marrow	UBERON:0002371	90.48	gold quality
left ovary	UBERON:0002119	90.47	gold quality
muscle of leg	UBERON:0001383	90.16	gold quality
buccal mucosa cell	CL:0002336	89.97	gold quality
esophagus mucosa	UBERON:0002469	89.84	gold quality
tendon	UBERON:0000043	89.83	gold quality
right adrenal gland cortex	UBERON:0035827	89.81	gold quality
gastrocnemius	UBERON:0001388	89.76	gold quality
right ovary	UBERON:0002118	89.64	gold quality
ectocervix	UBERON:0012249	89.62	gold quality
tibial nerve	UBERON:0001323	89.35	gold quality
islet of Langerhans	UBERON:0000006	89.31	gold quality
right lobe of thyroid gland	UBERON:0001119	89.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	967.76
E-ANND-3	no	3.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

235 targeting MTMR3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-497-5P	99.92	71.83	2674

Literature-anchored findings (GeneRIF, showing 21)

• MTMR3 shares similar phosphatase activity and substrate specificity with its homologous proteins MTM1 and MTMR3 (PMID:11846405)
• analysis of MTMR3 phosphoinositide binding domain properties (PMID:15840652)
• A phylogenetic study revealing co-evolution of myotubularins with PI 3-kinase class III complex (PMID:18774718)
• Autophagosome formation was triggered by the overexpression of a dominant-negative inactive mutant of Myotubularin-related phosphatase 3 (MTMR3). (PMID:20059746)
• Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates cell migration. (PMID:23154468)
• Data suggest MTMR3, PIKFYVE (phosphoinositide kinase FYVE), and their product phosphatidylinositol 5-phosphate are involved in activation of RAC1 (rho family small GTP binding protein); this process regulates migration/invasion of carcinoma/sarcoma. (PMID:24840251)
• Our results suggest that the MTMR3 gene is shared between IgA nephropathy and lupus nephritis in the northern Chinese population, further highlighting the role of autophagy in systemic lupus erythematosus. (PMID:24943867)
• cloning, expression, purification and crystallization of human myotubularin-related protein 3 encompassing the PH-GRAM and the phosphatase catalytic domain are reported (PMID:25195900)
• These results indicate that MTMR3 may play an important role in the progression of CRC and suggest that siRNA mediated silencing of MTMR3 could be an effective tool in CRC treatment. (PMID:25215329)
• myotubularin-related protein 3 and myotubularin-related protein 4 may act as a bridge between CEP55 and polo-like kinase 1, ensuring proper CEP55 phosphorylation and regulating CEP55 recruitment to the midbody. (PMID:25659891)
• the rs713875 IBD risk polymorphism increases MTMR3 expression, which modulates pattern recognition receptor (PRR)-induced outcomes, including increased induced caspase-1 activation (PMID:26240347)
• Data suggest MTMR3 has multiple functions in regulation of autophagy; one mechanism appears to be direct interaction between MTMR3 and mTORC1 (MTOR, mLST8, raptor) which inhibits phosphorylation activity of mTORC1; MTMR3 is localized to Golgi apparatus. (PMID:26787466)
• Association of MTMR3 rs12537 at miR-181a binding site with rheumatoid arthritis and systemic lupus erythematosus risk in Egyptian patients. (PMID:31444373)
• Study demonstrated that high levels of MTMR3 were associated with relapsefree survival and the triplenegative breast cancer subtype, as well as with a protumorigenic function in human breast cancer cells. Its knockdown suppressed proliferation and colony formation through cell cycle arrest and autophagy in MDAMB231 cells. These results provided novel insights into the pathological mechanism of breast cancer. (PMID:31485632)
• Three SNPs of FCRL3 and one SNP of MTMR3 are associated with immunoglobulin A nephropathy risk. (PMID:31780315)
• Exosomal miR-1910-3p promotes proliferation, metastasis, and autophagy of breast cancer cells by targeting MTMR3 and activating the NF-kappaB signaling pathway. (PMID:32531321)
• Circular RNA MCTP2 inhibits cisplatin resistance in gastric cancer by miR-99a-5p-mediated induction of MTMR3 expression. (PMID:33198772)
• miR-100-5p is upregulated in multiple myeloma and involves in the pathogenesis of multiple myeloma through targeting MTMR3. (PMID:37014739)
• MTMR3 risk alleles enhance Toll Like Receptor 9-induced IgA immunity in IgA nephropathy. (PMID:37414396)
• Breast cancer risk is associated with the HULC rs7763881, MTMR3 rs12537 polymorphisms, and serum levels of HULC and MTMR3 in Egyptian patients. (PMID:37910386)
• MTMR3 belongs to the myotubularin family of phosphoinositides phosphatases (PMID:9736772)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtmr3	ENSDARG00000093364
danio_rerio	mtmr3	ENSDARG00000098201
mus_musculus	Mtmr3	ENSMUSG00000034354
rattus_norvegicus	Mtmr3	ENSRNOG00000007120
drosophila_melanogaster	mtm	FBGN0025742
drosophila_melanogaster	Sbf	FBGN0025802
drosophila_melanogaster	Mtmr6	FBGN0028497
drosophila_melanogaster	CG14411	FBGN0030582
drosophila_melanogaster	CG3632	FBGN0030735
drosophila_melanogaster	CG5026	FBGN0035945
caenorhabditis_elegans	mtm-1	WBGENE00003475
caenorhabditis_elegans		WBGENE00003476
caenorhabditis_elegans		WBGENE00003477
caenorhabditis_elegans		WBGENE00003478
caenorhabditis_elegans		WBGENE00003479
caenorhabditis_elegans	mtm-10	WBGENE00021683

Paralogs (13): MTMR7 (ENSG00000003987), MTMR11 (ENSG00000014914), MTMR1 (ENSG00000063601), MTMR2 (ENSG00000087053), SBF1 (ENSG00000100241), MTMR8 (ENSG00000102043), MTMR9 (ENSG00000104643), MTMR4 (ENSG00000108389), SBF2 (ENSG00000133812), MTMR6 (ENSG00000139505), MTMR12 (ENSG00000150712), MTMR10 (ENSG00000166912), MTM1 (ENSG00000171100)

Protein

Protein identifiers

Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR3 — Q13615 (reviewed: Q13615)

Alternative names: FYVE domain-containing dual specificity protein phosphatase 1, Myotubularin-related protein 3, Phosphatidylinositol-3,5-bisphosphate 3-phosphatase, Phosphatidylinositol-3-phosphate phosphatase, Zinc finger FYVE domain-containing protein 10

All UniProt accessions (3): Q13615, C9JLU3, G5E953

UniProt curated annotations — full annotation on UniProt →

Function. Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylinositol 5-phosphate. Decreases the levels of phosphatidylinositol 3-phosphate, a phospholipid found in cell membranes where it acts as key regulator of both cell signaling and intracellular membrane traffic. Could also have a molecular sequestering/adapter activity and regulate biological processes independently of its phosphatase activity. It includes the regulation of midbody abscission during mitotic cytokinesis.

Subunit / interactions. Forms heterodimers with MTMR4 that recruit both CEP55 and PLK1; occurs during early mitosis, regulates the phosphorylation of CEP55 by PLK1 and its recruitment to the midbody where it mediates cell abscission.

Subcellular location. Cytoplasm. Cytosol. Membrane.

Post-translational modifications. Phosphorylated by CDK1 during mitosis.

Domain organisation. The coiled coil domain mediates the interaction between MTMR3 and MTMR4. It is essential to bring together CEP55 and PLK1 during mitotic abscission.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13615-1	B, FYVE-DSP1b	yes
Q13615-2	A, FYVE-DSP1a
Q13615-3	C, FYVE-DSP1c

RefSeq proteins (3): NP_066576, NP_694690, NP_694691 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000306	Znf_FYVE	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR010569	Myotubularin-like_Pase_dom	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR016130	Tyr_Pase_AS	Active_site
IPR017455	Znf_FYVE-rel	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR030564	Myotubularin	Family
IPR035888	MTMR3_PH-GRAM	Domain
IPR046352	MTMR3_PTP	Domain

Pfam: PF01363, PF06602

Enzyme classification (BRENDA):

• EC 3.1.3.95 — phosphatidylinositol-3,5-bisphosphate 3-phosphatase (BRENDA: 2 organisms, 16 substrates, 1 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 5 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + phosphate (RHEA:12316)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + phosphate (RHEA:39019)
• 1,2-dioctanoyl-sn-glycero-3-phospho-(1-D-myo-inositol-3-phosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol) + phosphate (RHEA:42328)
• 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + phosphate (RHEA:45636)
• 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol) + phosphate (RHEA:45640)

UniProt features (60 total): binding site 29, modified residue 9, region of interest 7, compositionally biased region 4, splice variant 2, mutagenesis site 2, chain 1, domain 1, coiled-coil region 1, active site 1, zinc finger region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13615-F1	66.94	0.43

Functional residue map

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

Catalytic / active sites (1): 413 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (29): 326; 326; 351; 351; 352; 352; 414; 414; 415; 415; 416; 416 …

Post-translational modifications (9): 8, 613, 633, 647, 651, 731, 906, 909, 1064

Mutagenesis-validated functional residues (2):

Position	Phenotype
413	loss of lipid phosphatase activity. no effect on function in mitotic abscission.
1174	loss of function in mitotic abscission. decreased interaction with plk1.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-1430728	Metabolism
R-HSA-1483255	PI Metabolism
R-HSA-1483257	Phospholipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-9612973	Autophagy

MSigDB gene sets: 267 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_VACUOLE_ORGANIZATION, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, RACCACAR_AML_Q6, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CYTOKINETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_PHOSPHOLIPID_METABOLIC_PROCESS

GO Biological Process (11): protein dephosphorylation (GO:0006470), phosphatidylinositol biosynthetic process (GO:0006661), macroautophagy (GO:0016236), cellular response to glucose starvation (GO:0042149), phosphatidylinositol dephosphorylation (GO:0046856), regulation of phosphatidylinositol dephosphorylation (GO:0060304), midbody abscission (GO:0061952), phosphatidylinositol 5-phosphate metabolic process (GO:1904562), regulation of autophagosome assembly (GO:2000785), lipid metabolic process (GO:0006629), dephosphorylation (GO:0016311)

GO Molecular Function (11): phosphatidylinositol-3-phosphate phosphatase activity (GO:0004438), protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), zinc ion binding (GO:0008270), protein phosphatase binding (GO:0019903), phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity (GO:0052629), molecular adaptor activity (GO:0060090), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Autophagy	1
PI Metabolism	1
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	3
cellular anatomical structure	3
phosphatidylinositol metabolic process	2
autophagosome assembly	2
binding	2
dephosphorylation	1
protein modification process	1
biosynthetic process	1
autophagy	1
cellular response to starvation	1
phospholipid dephosphorylation	1
regulation of lipid metabolic process	1
regulation of dephosphorylation	1
phosphatidylinositol dephosphorylation	1
regulation of phosphorus metabolic process	1
regulation of macromolecule metabolic process	1
membrane organization	1
mitotic cytokinetic process	1
glycerophospholipid metabolic process	1
regulation of vacuole organization	1
regulation of organelle assembly	1
primary metabolic process	1
phosphate-containing compound metabolic process	1
phosphatidylinositol monophosphate phosphatase activity	1
transition metal ion binding	1
phosphatase binding	1
phosphatidylinositol-3,5-bisphosphate phosphatase activity	1
molecular_function	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTMR3	PIK3C3	Q8NEB9	601
MTMR3	HORMAD2	Q8N7B1	541
MTMR3	AKT1	P31749	428
MTMR3	MAMLD1	Q13495	424
MTMR3	PDPK1	O15530	414
MTMR3	MTMR4	Q9NYA4	413
MTMR3	WDR81	Q562E7	400
MTMR3	EIF4EBP1	Q13541	396
MTMR3	CFLAR	O15519	393
MTMR3	ZMAT5	Q9UDW3	390
MTMR3	ASCC2	Q9H1I8	389
MTMR3	STX17	P56962	387
MTMR3	AMBRA1	Q9C0C7	384
MTMR3	SBF1	O95248	379
MTMR3	WIPI1	Q5MNZ9	370

IntAct

78 interactions, top by confidence:

A	B	Type	Score
MED18	MED19	psi-mi:“MI:0914”(association)	0.840
HDAC11	CLUH	psi-mi:“MI:0914”(association)	0.640
AIPL1	PDE5A	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
MTMR3	EXOSC5	psi-mi:“MI:0915”(physical association)	0.560
MTMR3	LONRF1	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
AURKA	WDR62	psi-mi:“MI:0914”(association)	0.530
ALOX5	DDHD2	psi-mi:“MI:0914”(association)	0.530
MTMR3	MTOR	psi-mi:“MI:0915”(physical association)	0.500
MTMR3	RPTOR	psi-mi:“MI:0915”(physical association)	0.500
MTMR3	MTOR	psi-mi:“MI:0914”(association)	0.500
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
MTMR4	MTMR3	psi-mi:“MI:0914”(association)	0.420
MTMR3	MTMR4	psi-mi:“MI:2364”(proximity)	0.420
MTMR3	FGFR2	psi-mi:“MI:0915”(physical association)	0.370
PCNA	MTMR3	psi-mi:“MI:0915”(physical association)	0.370
EXOSC7	MTMR3	psi-mi:“MI:0915”(physical association)	0.370
MTMR3	EXOSC1	psi-mi:“MI:0915”(physical association)	0.370
EXOSC1	MTMR3	psi-mi:“MI:0915”(physical association)	0.370
MTMR3	EXOSC8	psi-mi:“MI:0915”(physical association)	0.370
EXOSC8	MTMR3	psi-mi:“MI:0915”(physical association)	0.370
MTMR3	HIVEP1	psi-mi:“MI:0915”(physical association)	0.370
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (120): MTMR3 (Affinity Capture-MS), MTMR3 (Affinity Capture-MS), MTMR3 (Affinity Capture-MS), MTMR3 (Affinity Capture-MS), MTMR3 (Affinity Capture-MS), MTMR3 (Affinity Capture-MS), MTOR (Affinity Capture-Western), MTOR (Affinity Capture-MS), MTMR4 (Affinity Capture-MS), MLST8 (Affinity Capture-Western), RPTOR (Affinity Capture-Western), MTMR3 (Affinity Capture-MS), MTMR4 (Affinity Capture-MS), PLK1 (Affinity Capture-MS), MTMR3 (Affinity Capture-MS)

ESM2 similar proteins: A2VE78, A5PK16, A6QP29, B1AVH7, B5DFA1, C0HAC0, D2H0G5, D2HNY3, O15040, P31152, P41002, P51944, Q13615, Q2YDQ5, Q32NM1, Q3UMR0, Q400C9, Q5F479, Q5M9H0, Q5PQT2, Q5REW9, Q5RF77, Q5XGG5, Q69ZT1, Q6NYX6, Q6R653, Q6ZW76, Q7T0L6, Q7TNH6, Q80TI1, Q810L3, Q86XL3, Q8BVF9, Q8C2S5, Q8IV13, Q8IV45, Q8JZL1, Q8K296, Q8K4F8, Q8NFM7

Diamond homologs: A0A0D1E015, A0JMD2, A1CEK1, A1DFP5, A2QWA2, A4QTV1, A8QCE4, A8XJZ8, B0G126, B0WAQ0, B3MT31, B3P851, B4G2G5, B4IC49, B4JHI7, B4K982, B4M140, B4NFJ7, B4PRU6, D2H5P6, D3ZVP7, D4A8G9, E1BLZ4, F1MM41, F7EP40, O13821, O14964, O59722, O76902, O95405, O96838, P0CS26, P0CS27, P34756, P40343, Q05B78, Q08CN9, Q0CJV3, Q0P4S0, Q0U4Z8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MTMR3	“down-regulates activity”	MTOR
MTMR3	“down-regulates activity”	mTORC1
MTMR3	“down-regulates quantity”	“1-phosphatidyl-1D-myo-inositol 3-phosphate(3-)”	“chemical modification”
MTMR3	“up-regulates quantity”	1-phosphatidyl-1D-myo-inositol(1-)	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	78.4×	6e-10
Activation of BAD and translocation to mitochondria	6	76.1×	1e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	67.2×	2e-08
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA	5	52.9×	9e-07
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	5	52.9×	9e-07
KSRP (KHSRP) binds and destabilizes mRNA	5	52.9×	9e-07
Activation of BH3-only proteins	6	49.6×	1e-07
RHO GTPases activate PKNs	7	37.0×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
RNA catabolic process	5	30.0×	5e-04
protein targeting	5	24.1×	5e-04
negative regulation of autophagy	5	17.1×	1e-03
intracellular protein localization	6	8.3×	7e-03
protein phosphorylation	9	8.1×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4534 predictions. Top by Δscore:

Variant	Effect	Δscore
22:29883355:GCCCG:G	donor_gain	1.0000
22:29890798:G:GT	donor_gain	1.0000
22:29957033:CA:C	acceptor_loss	1.0000
22:29957034:A:AG	acceptor_gain	1.0000
22:29957034:A:G	acceptor_loss	1.0000
22:29957035:G:GT	acceptor_gain	1.0000
22:29957035:GA:G	acceptor_gain	1.0000
22:29957035:GAC:G	acceptor_gain	1.0000
22:29957035:GACT:G	acceptor_gain	1.0000
22:29957035:GACTT:G	acceptor_gain	1.0000
22:29957085:TTTG:T	donor_gain	1.0000
22:29957087:TGG:T	donor_loss	1.0000
22:29957088:GGT:G	donor_loss	1.0000
22:29957089:G:GG	donor_gain	1.0000
22:29957089:GTAA:G	donor_loss	1.0000
22:29957090:T:A	donor_loss	1.0000
22:29971811:A:T	donor_gain	1.0000
22:29971832:GCT:G	donor_gain	1.0000
22:29978530:AGG:A	donor_loss	1.0000
22:29978931:C:CA	acceptor_gain	1.0000
22:29979053:G:GG	donor_gain	1.0000
22:29988559:TCAG:T	donor_loss	1.0000
22:29988561:AG:A	donor_loss	1.0000
22:29988562:GGTA:G	donor_loss	1.0000
22:29991478:T:G	acceptor_gain	1.0000
22:29991499:A:AG	acceptor_gain	1.0000
22:29991499:AAAAG:A	acceptor_gain	1.0000
22:29991500:A:G	acceptor_gain	1.0000
22:29991502:A:AG	acceptor_loss	1.0000
22:29998759:AGG:A	acceptor_gain	1.0000

AlphaMissense

7893 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:29978957:G:A	G39R	1.000
22:29978957:G:C	G39R	1.000
22:29978958:G:A	G39E	1.000
22:29978958:G:T	G39V	1.000
22:29979009:C:A	S56Y	1.000
22:29979009:C:T	S56F	1.000
22:29979014:T:G	Y58D	1.000
22:29979018:G:C	R59T	1.000
22:29979019:A:C	R59S	1.000
22:29979019:A:T	R59S	1.000
22:29979021:T:C	L60P	1.000
22:29988529:T:C	L87P	1.000
22:29991538:T:A	W110R	1.000
22:29991538:T:C	W110R	1.000
22:29991592:T:C	F128L	1.000
22:29991594:C:A	F128L	1.000
22:29991594:C:G	F128L	1.000
22:29998826:T:A	W176R	1.000
22:29998826:T:C	W176R	1.000
22:30002956:T:C	F212L	1.000
22:30002958:C:A	F212L	1.000
22:30002958:C:G	F212L	1.000
22:30002960:G:C	R213T	1.000
22:30002960:G:T	R213M	1.000
22:30007153:G:C	Q237H	1.000
22:30007153:G:T	Q237H	1.000
22:30007155:C:A	P238Q	1.000
22:30007190:G:C	D250H	1.000
22:30007991:C:A	A323D	1.000
22:30007999:A:G	N326D	1.000

dbSNP variants (sampled 300 via entrez): RS1000014903 (22:30025903 T>C), RS1000017635 (22:29890985 C>T), RS1000019111 (22:30005441 C>G,T), RS1000024493 (22:29965453 G>A), RS1000060102 (22:30023000 T>C), RS1000088056 (22:29902699 G>A,T), RS1000135080 (22:30000344 C>T), RS1000136656 (22:29908300 G>A), RS1000138996 (22:29907265 C>T), RS1000209504 (22:29982363 A>C,G), RS1000214947 (22:29936753 A>G), RS1000235457 (22:29908098 A>C,G), RS1000259449 (22:30023080 C>G,T), RS1000304518 (22:29982729 T>G), RS1000325304 (22:29953461 T>C)

Disease associations

OMIM: gene MIM:603558 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST000531_1	Inflammatory bowel disease (early onset)	2.000000e-09
GCST000879_44	Crohn’s disease	7.000000e-12
GCST001009_3	Nephropathy	2.000000e-09
GCST001140_4	Lung cancer	6.000000e-13
GCST001364_4	IgA nephropathy	1.000000e-11
GCST001725_109	Inflammatory bowel disease	3.000000e-14
GCST002222_39	LDL cholesterol	1.000000e-08
GCST003974_1	Tonsillectomy	1.000000e-09
GCST003995_2	Tonsillectomy	3.000000e-34
GCST004070_1	Cerebrospinal P-tau181p levels	4.000000e-06
GCST004131_67	Inflammatory bowel disease	4.000000e-08
GCST004132_86	Crohn’s disease	8.000000e-07
GCST004233_26	LDL cholesterol levels	3.000000e-09
GCST004602_244	Mean corpuscular volume	2.000000e-14
GCST005014_124	Tonsillectomy	3.000000e-34
GCST005851_15	Delirium	1.000000e-06
GCST006976_37	Macular thickness	6.000000e-17
GCST007515_11	Type 2 diabetes	6.000000e-13
GCST007517_26	Type 2 diabetes	4.000000e-11
GCST008059_251	Estimated glomerular filtration rate	3.000000e-10
GCST008295_19	Number of decayed, missing and filled tooth surfaces or use of dentures	2.000000e-09
GCST008306_20	Dentures	2.000000e-08
GCST008747_137	Estimated glomerular filtration rate	9.000000e-10
GCST009379_303	Type 2 diabetes	1.000000e-12
GCST010002_80	Refractive error	2.000000e-09
GCST012073_22	Behcet’s disease	2.000000e-06
GCST90002383_104	Hematocrit	7.000000e-13
GCST90002384_498	Hemoglobin	1.000000e-15
GCST90002385_577	High light scatter reticulocyte count	1.000000e-10
GCST90002386_532	High light scatter reticulocyte percentage of red cells	1.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0004763	p-tau measurement
EFO:0010078	dentures
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	6
bisphenol A	increases methylation, decreases methylation, increases expression, affects cotreatment	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	increases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Doxorubicin	decreases expression	1
Ozone	increases abundance, affects expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1XW	Abcam HeLa MTMR3 KO	Cancer cell line	Female
CVCL_SZ29	HAP1 MTMR3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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