TMEM109

Summary

TMEM109 (transmembrane protein 109, HGNC:28771) is a protein-coding gene on chromosome 11q12.2, encoding Voltage-gated monoatomic cation channel TMEM109 (Q9BVC6). Functions as a voltage-gated monoatomic cation channel permeable to both potassium and calcium.

Predicted to enable voltage-gated monoatomic cation channel activity. Acts upstream of or within cellular response to gamma radiation and negative regulation of programmed cell death. Located in extracellular exosome.

Source: NCBI Gene 79073 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 31 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_024092

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28771
Approved symbol	TMEM109
Name	transmembrane protein 109
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC5508, SND3, hSND3, Mg23
Ensembl gene	ENSG00000110108
Ensembl biotype	protein_coding
OMIM	619168
Entrez	79073

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000227525, ENST00000536171, ENST00000540280, ENST00000715796, ENST00000888772, ENST00000888773, ENST00000888774, ENST00000888775, ENST00000888776, ENST00000888777

RefSeq mRNA: 1 — MANE Select: NM_024092 NM_024092

CCDS: CCDS7996

Canonical transcript exons

ENST00000227525 — 4 exons

Exon	Start	End
ENSE00000721174	60920886	60920988
ENSE00000851436	60919686	60919930
ENSE00000991011	60921774	60923443
ENSE00004027949	60914158	60914268

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.2592 / max 291.0785, expressed in 1816 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114523	45.6099	1814
114522	5.8419	1688
114519	2.0800	1251
114520	0.6978	424
114524	0.6858	381
114521	0.3438	172

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ascending aorta	UBERON:0001496	97.93	gold quality
thoracic aorta	UBERON:0001515	97.93	gold quality
lower esophagus mucosa	UBERON:0035834	97.92	gold quality
right coronary artery	UBERON:0001625	97.85	gold quality
apex of heart	UBERON:0002098	97.84	gold quality
descending thoracic aorta	UBERON:0002345	97.84	gold quality
body of uterus	UBERON:0009853	97.74	gold quality
aorta	UBERON:0000947	97.64	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.60	gold quality
lower esophagus	UBERON:0013473	97.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.58	gold quality
left coronary artery	UBERON:0001626	97.55	gold quality
tibial nerve	UBERON:0001323	97.48	gold quality
popliteal artery	UBERON:0002250	97.47	gold quality
tibial artery	UBERON:0007610	97.47	gold quality
ectocervix	UBERON:0012249	97.45	gold quality
coronary artery	UBERON:0001621	97.40	gold quality
right lung	UBERON:0002167	97.39	gold quality
endocervix	UBERON:0000458	97.35	gold quality
left uterine tube	UBERON:0001303	97.30	gold quality
right ovary	UBERON:0002118	97.09	gold quality
esophagus	UBERON:0001043	97.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.99	gold quality
left ovary	UBERON:0002119	96.97	gold quality
upper lobe of left lung	UBERON:0008952	96.95	gold quality
mucosa of stomach	UBERON:0001199	96.92	gold quality
omental fat pad	UBERON:0010414	96.88	gold quality
peritoneum	UBERON:0002358	96.86	gold quality
skin of leg	UBERON:0001511	96.79	gold quality
right lobe of thyroid gland	UBERON:0001119	96.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.60
E-CURD-112	yes	10.16
E-MTAB-6379	no	245.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting TMEM109, 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-6798-5P	100.00	65.77	699
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119

Literature-anchored findings (GeneRIF, showing 2)

• MG23 is an essential component of ER-generated lethal signals provoked upon DNA damage, specifying cell fate under pathophysiological conditions. (PMID:20060811)
• MG23 plays a protective role against UVC by accumulating alphaBC in the close vicinity of the ER (PMID:23542032)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-9i23.15	ENSDARG00000093997
mus_musculus	Tmem109	ENSMUSG00000034659
rattus_norvegicus	Tmem109	ENSRNOG00000028017

Protein

Protein identifiers

Voltage-gated monoatomic cation channel TMEM109 — Q9BVC6 (reviewed: Q9BVC6)

Alternative names: Mitsugumin-23, Transmembrane protein 109

All UniProt accessions (1): Q9BVC6

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a voltage-gated monoatomic cation channel permeable to both potassium and calcium. Plays a role in the cellular response to DNA damage.

Subunit / interactions. Homooligomer. Interacts with CRYAB; in the cellular response to DNA damage.

Subcellular location. Nucleus outer membrane. Endoplasmic reticulum membrane. Sarcoplasmic reticulum membrane.

RefSeq proteins (1): NP_076997* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039492	TMEM109	Family

Pfam: PF14965

Catalyzed reactions (Rhea), 2 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)

UniProt features (9 total): topological domain 4, transmembrane region 3, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BVC6-F1	67.86	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 221 (showing top): GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GCANCTGNY_MYOD_Q6, CMYB_01, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_CELLULAR_RESPONSE_TO_GAMMA_RADIATION, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, GTGCCTT_MIR506, BROWNE_HCMV_INFECTION_48HR_DN, BROWNE_HCMV_INFECTION_24HR_UP

GO Biological Process (6): intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), negative regulation of programmed cell death (GO:0043069), cellular response to gamma radiation (GO:0071480), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (2): voltage-gated monoatomic cation channel activity (GO:0022843), protein binding (GO:0005515)

GO Cellular Component (9): nuclear outer membrane (GO:0005640), sarcoplasmic reticulum membrane (GO:0033017), monoatomic ion channel complex (GO:0034702), extracellular exosome (GO:0070062), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear outer membrane-endoplasmic reticulum membrane network	2
intracellular membrane-bounded organelle	2
intrinsic apoptotic signaling pathway in response to DNA damage	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
programmed cell death	1
regulation of programmed cell death	1
negative regulation of cellular process	1
response to gamma radiation	1
cellular response to ionizing radiation	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
voltage-gated monoatomic ion channel activity	1
monoatomic cation channel activity	1
binding	1
nuclear membrane	1
organelle outer membrane	1
endoplasmic reticulum membrane	1
sarcoplasmic reticulum	1
bounding membrane of organelle	1
transmembrane transporter complex	1
extracellular vesicle	1
cytoplasm	1
endomembrane system	1
organelle membrane	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
endoplasmic reticulum	1
sarcoplasm	1

Protein interactions and networks

STRING

1363 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM109	TMEM41A	Q96HV5	526
TMEM109	TMEM126A	Q9H061	479
TMEM109	ZCCHC24	Q8N2G6	478
TMEM109	SEC11C	Q9BY50	456
TMEM109	HYCC1	Q9BYI3	454
TMEM109	MS4A10	Q96PG2	445
TMEM109	TPM1	P09493	427
TMEM109	UHRF2	Q96PU4	421
TMEM109	STT3A	P46977	420
TMEM109	CSNK2A1	P19138	411
TMEM109	TMEM151B	Q8IW70	408
TMEM109	CCDC185	Q8N715	392
TMEM109	MAB21L3	Q8N8X9	384
TMEM109	GLB1L2	Q8IW92	381
TMEM109	FAM184B	Q9ULE4	381

IntAct

117 interactions, top by confidence:

A	B	Type	Score
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
SLC12A2	CLGN	psi-mi:“MI:0914”(association)	0.640
	DDX3X	psi-mi:“MI:0914”(association)	0.630
TMEM109	SPINT1	psi-mi:“MI:0915”(physical association)	0.560
GPX8	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
AQP2	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
GOLM1	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
TMEM109	MTIF3	psi-mi:“MI:0915”(physical association)	0.560
TMEM109	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
SPINT1	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
MGST3	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
TMEM109	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
AQP9	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
PDZK1IP1	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
TMEM52B	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
STOM	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
RNF170	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
TMEM80	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
SLC18A2	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
Rassf1	VAPB	psi-mi:“MI:0915”(physical association)	0.560
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
TMEM43	ENDOD1	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
TMEM109	PGRMC2	psi-mi:“MI:0915”(physical association)	0.400
KISS1R	ERLIN1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (169): TMEM109 (Affinity Capture-MS), TMEM109 (Affinity Capture-MS), CRYAB (Two-hybrid), CRYAB (Affinity Capture-Western), TMEM109 (Affinity Capture-MS), TMEM109 (Proximity Label-MS), TMEM109 (Proximity Label-MS), TMEM109 (Proximity Label-MS), TMEM109 (Affinity Capture-MS), TMEM109 (Affinity Capture-MS), TMEM109 (Affinity Capture-MS), TMEM109 (Affinity Capture-MS), TMEM109 (Affinity Capture-MS), TMEM109 (Affinity Capture-MS), TMEM109 (Affinity Capture-MS)

ESM2 similar proteins: A0A060L102, A0A060L4I9, A0A1I9R3Y6, A2XL05, A6MGW7, C0HM28, C3S7F0, C3S7F1, O04925, P13436, P21641, P29109, P29110, P29111, P29525, P29526, P29527, P29528, P29529, P29530, P29531, P93829, Q00650, Q10EK7, Q1RMH4, Q39165, Q42431, Q42574, Q42980, Q43284, Q43804, Q45W86, Q45W87, Q52NJ0, Q647G3, Q647G4, Q647G5, Q68F33, Q6GM19, Q6J1J8

Diamond homologs: O77751, Q3UBX0, Q6AYQ4, Q9BVC6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

465 predictions. Top by Δscore:

Variant	Effect	Δscore
11:60919927:AGAGG:A	donor_loss	1.0000
11:60919928:GAG:G	donor_gain	1.0000
11:60919930:GGT:G	donor_loss	1.0000
11:60919931:G:T	donor_loss	1.0000
11:60920884:A:AG	acceptor_gain	1.0000
11:60920885:G:GA	acceptor_gain	1.0000
11:60920885:GT:G	acceptor_gain	1.0000
11:60920885:GTC:G	acceptor_gain	1.0000
11:60920885:GTCTT:G	acceptor_gain	1.0000
11:60920985:GCTG:G	donor_gain	1.0000
11:60920987:TGGT:T	donor_loss	1.0000
11:60920989:G:GG	donor_gain	1.0000
11:60920989:GT:G	donor_loss	1.0000
11:60920990:TGAG:T	donor_loss	1.0000
11:60920991:GAGTG:G	donor_loss	1.0000
11:60921771:CAG:C	acceptor_loss	1.0000
11:60921772:A:AG	acceptor_gain	1.0000
11:60921772:A:G	acceptor_loss	1.0000
11:60921772:AGGT:A	acceptor_gain	1.0000
11:60921773:G:GG	acceptor_gain	1.0000
11:60921773:GGT:G	acceptor_gain	1.0000
11:60921773:GGTG:G	acceptor_gain	1.0000
11:60919684:A:AG	acceptor_gain	0.9900
11:60919685:G:GG	acceptor_gain	0.9900
11:60919862:A:G	donor_gain	0.9900
11:60919937:A:T	donor_gain	0.9900
11:60920882:A:AG	acceptor_gain	0.9900
11:60920883:C:G	acceptor_gain	0.9900
11:60920883:CAG:C	acceptor_loss	0.9900
11:60920885:G:A	acceptor_loss	0.9900

AlphaMissense

1494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:60921836:G:A	G135R	0.977
11:60921836:G:C	G135R	0.977
11:60921833:T:A	W134R	0.975
11:60921833:T:C	W134R	0.975
11:60921947:T:C	F172L	0.967
11:60921949:C:A	F172L	0.967
11:60921949:C:G	F172L	0.967
11:60921925:G:C	K164N	0.948
11:60921925:G:T	K164N	0.948
11:60921944:G:C	G171R	0.930
11:60921846:C:A	A138D	0.929
11:60920926:C:T	S93F	0.928
11:60921837:G:A	G135E	0.927
11:60921828:T:G	L132R	0.926
11:60921835:G:C	W134C	0.910
11:60921835:G:T	W134C	0.910
11:60921828:T:C	L132P	0.901
11:60922068:T:A	L212H	0.901
11:60920932:C:A	A95D	0.897
11:60921923:A:G	K164E	0.897
11:60921816:T:A	V128D	0.896
11:60922095:G:C	R221P	0.892
11:60921999:T:A	L189H	0.891
11:60920926:C:A	S93Y	0.890
11:60921945:G:A	G171D	0.890
11:60922031:A:C	S200R	0.888
11:60922033:C:A	S200R	0.888
11:60922033:C:G	S200R	0.888
11:60922078:G:C	K215N	0.888
11:60922078:G:T	K215N	0.888

dbSNP variants (sampled 300 via entrez): RS1000342054 (11:60923591 G>A), RS1000544818 (11:60921287 G>A), RS1000671663 (11:60914371 A>C,G), RS1000832344 (11:60918040 T>G), RS1001217065 (11:60915326 A>G), RS1001810936 (11:60922624 T>C), RS1002229211 (11:60914039 C>T), RS1002276577 (11:60917322 T>C), RS1002841736 (11:60921641 A>G), RS1002946140 (11:60914361 G>C), RS1003235826 (11:60912399 G>A), RS1003283322 (11:60915696 T>G), RS1003356632 (11:60915969 T>A,C), RS1003587556 (11:60922858 C>G), RS1003593869 (11:60912692 C>T)

Disease associations

OMIM: gene MIM:619168 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725036 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.27	Kd	5.418	nM	CHEMBL5653589
8.27	ED50	5.418	nM	CHEMBL5653589
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149605: Binding affinity to human TMEM109 incubated for 45 mins by Kinobead based pull down assay	kd	0.0054	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178933: Inhibition of Mitsugumin 23 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment	2
sodium arsenite	increases expression, decreases expression	2
bisphenol S	affects expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Doxorubicin	affects expression, decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	increases expression	1
sodium arsenate	increases abundance, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
pinostrobin	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Clozapine	affects cotreatment, increases expression	1
Copper	decreases expression, affects binding	1
Cuprizone	affects cotreatment, increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Furaldehyde	affects cotreatment, increases expression	1
Haloperidol	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652647	Binding	Binding affinity to human TMEM109 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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