TMEM115

Summary

TMEM115 (transmembrane protein 115, HGNC:30055) is a protein-coding gene on chromosome 3p21.31, encoding Transmembrane protein 115 (Q12893). May play a role in retrograde transport of proteins from the Golgi to the endoplasmic reticulum.

Enables identical protein binding activity. Involved in retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum. Located in Golgi cisterna membrane; Golgi transport complex; and nucleus.

Source: NCBI Gene 11070 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• MANE Select transcript: NM_007024

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30055
Approved symbol	TMEM115
Name	transmembrane protein 115
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	PL6
Ensembl gene	ENSG00000126062
Ensembl biotype	protein_coding
OMIM	607069
Entrez	11070

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000266025, ENST00000901094, ENST00000972195

RefSeq mRNA: 1 — MANE Select: NM_007024 NM_007024

CCDS: CCDS2828

Canonical transcript exons

ENST00000266025 — 2 exons

Exon	Start	End
ENSE00000860752	50358213	50359521
ENSE00001081145	50354750	50355547

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 91.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0013 / max 103.8190, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42337	19.2575	1813
42338	0.7439	482

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	91.79	gold quality
apex of heart	UBERON:0002098	91.71	gold quality
skin of leg	UBERON:0001511	91.54	gold quality
left adrenal gland	UBERON:0001234	90.91	gold quality
right lobe of thyroid gland	UBERON:0001119	90.88	gold quality
mucosa of transverse colon	UBERON:0004991	90.86	gold quality
left lobe of thyroid gland	UBERON:0001120	90.83	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.80	gold quality
skin of abdomen	UBERON:0001416	90.78	gold quality
lower esophagus	UBERON:0013473	90.78	gold quality
right adrenal gland	UBERON:0001233	90.77	gold quality
left adrenal gland cortex	UBERON:0035825	90.77	gold quality
right adrenal gland cortex	UBERON:0035827	90.72	gold quality
body of stomach	UBERON:0001161	90.64	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.62	gold quality
left coronary artery	UBERON:0001626	90.36	gold quality
right coronary artery	UBERON:0001625	90.22	gold quality
left uterine tube	UBERON:0001303	90.07	gold quality
mucosa of stomach	UBERON:0001199	90.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.96	gold quality
coronary artery	UBERON:0001621	89.81	gold quality
adrenal cortex	UBERON:0001235	89.79	gold quality
transverse colon	UBERON:0001157	89.77	gold quality
thoracic aorta	UBERON:0001515	89.77	gold quality
descending thoracic aorta	UBERON:0002345	89.73	gold quality
thyroid gland	UBERON:0002046	89.72	gold quality
ascending aorta	UBERON:0001496	89.66	gold quality
aorta	UBERON:0000947	89.50	gold quality
right atrium auricular region	UBERON:0006631	89.46	gold quality
popliteal artery	UBERON:0002250	89.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): VHL

miRNA regulators (miRDB)

33 targeting TMEM115, 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-7152-3P	99.97	67.47	849
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-6718-5P	97.24	68.15	553
HSA-MIR-410-5P	96.55	66.28	459
HSA-MIR-323B-5P	96.12	66.39	472
HSA-MIR-6726-5P	95.97	63.72	841
HSA-MIR-920	95.97	63.95	811
HSA-MIR-4300	95.85	64.56	1003
HSA-MIR-5591-5P	95.85	64.76	1002

Literature-anchored findings (GeneRIF, showing 1)

• Results establish that TMEM115 is an integral membrane protein of the Golgi stack regulating Golgi-to-ER retrograde transport and is likely to be part of the machinery of the COG complex. (PMID:24806965)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem115	ENSDARG00000055763
mus_musculus	Tmem115	ENSMUSG00000010045
rattus_norvegicus	Tmem115	ENSRNOG00000021899
drosophila_melanogaster	CG9536	FBGN0031818
caenorhabditis_elegans		WBGENE00008687

Protein

Protein identifiers

Transmembrane protein 115 — Q12893 (reviewed: Q12893)

Alternative names: Placental protein 6, Protein PL6

All UniProt accessions (2): Q12893, A0A024R2Y2

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in retrograde transport of proteins from the Golgi to the endoplasmic reticulum. May indirectly play a role in protein glycosylation in the Golgi.

Subunit / interactions. Homooligomer. Interacts with COPB1. May interact with LMAN1. Interacts with the COG complex; probably through COG3.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Expressed strongly in kidney and skeletal muscle, followed by liver, placenta, pancreas, and lung, with low amounts in heart and only traces in brain. Widely expressed with ubiquitous expression in epithelial tissues (at protein level).

Similarity. Belongs to the TMEM115 family.

RefSeq proteins (1): NP_008955* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013861	TMEM115/Pdh1/Rbl19	Family
IPR035952	Rhomboid-like_sf	Homologous_superfamily

Pfam: PF08551

UniProt features (14 total): topological domain 5, transmembrane region 4, region of interest 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12893-F1	79.11	0.47

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): 329

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6807878	COPI-mediated anterograde transport

MSigDB gene sets: 122 (showing top): RRAGTTGT_UNKNOWN, GCAAGGA_MIR502, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GGAMTNNNNNTCCY_UNKNOWN, HESSON_TUMOR_SUPPRESSOR_CLUSTER_3P21_3, AACWWCAANK_UNKNOWN, IRF7_01, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, GRE_C, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, CAAGGAT_MIR362, ACTWSNACTNY_UNKNOWN, GOCC_GOLGI_STACK

GO Biological Process (3): retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), negative regulation of cell population proliferation (GO:0008285), protein transport (GO:0015031)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): Golgi membrane (GO:0000139), nucleus (GO:0005634), Golgi apparatus (GO:0005794), Golgi cisterna membrane (GO:0032580), membrane (GO:0016020), COG complex (GO:0017119)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
Golgi apparatus	2
intracellular membrane-bounded organelle	2
Golgi vesicle transport	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein binding	1
binding	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
organelle membrane	1
Golgi cisterna	1
cellular anatomical structure	1
vesicle tethering complex	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM115	UBAC2	Q8NBM4	494
TMEM115	TMEM101	Q96IK0	472
TMEM115	TMEM208	Q9BTX3	468
TMEM115	TMEM59L	Q9UK28	445
TMEM115	RHBDD2	Q6NTF9	411
TMEM115	A0A1W2PP11	A0A1W2PP11	393
TMEM115	CDKN2A	P42771	392
TMEM115	PARL	Q9H300	391
TMEM115	CYB561D2	O14569	384
TMEM115	RHBDD3	Q9Y3P4	371
TMEM115	RHBDF1	Q96CC6	370
TMEM115	ZMYND10	O75800	369
TMEM115	STX16	O14662	369
TMEM115	RHBDL1	O75783	367
TMEM115	RHBDF2	Q6PJF5	351

IntAct

69 interactions, top by confidence:

A	B	Type	Score
TMEM115	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
SYNE4	TMEM115	psi-mi:“MI:0915”(physical association)	0.560
TMEM115	AQP6	psi-mi:“MI:0915”(physical association)	0.560
TMEM115	ASPG	psi-mi:“MI:0915”(physical association)	0.560
TMEM115	TMED8	psi-mi:“MI:0915”(physical association)	0.560
CYB5R3	TMEM115	psi-mi:“MI:0915”(physical association)	0.560
TMEM115	RABAC1	psi-mi:“MI:0915”(physical association)	0.560
TMEM115	HTATIP2	psi-mi:“MI:0915”(physical association)	0.560
TMEM115	MANBAL	psi-mi:“MI:0915”(physical association)	0.560
TMEM115	TMX2	psi-mi:“MI:0915”(physical association)	0.560
TMEM115	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
TMEM115		psi-mi:“MI:0915”(physical association)	0.560
TMEM115	LAMP2	psi-mi:“MI:0915”(physical association)	0.560
TMEM115	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.560
HTT	TMEM115	psi-mi:“MI:0915”(physical association)	0.560
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480

BioGRID (74): SYNE4 (Two-hybrid), TMEM115 (Two-hybrid), TMEM115 (Proximity Label-MS), TMEM115 (Proximity Label-MS), TMEM115 (Two-hybrid), TMEM115 (Affinity Capture-MS), TMEM115 (Affinity Capture-MS), TMEM115 (Affinity Capture-MS), TMEM115 (Proximity Label-MS), TMEM115 (Proximity Label-MS), TMEM115 (Affinity Capture-MS), TMEM115 (Proximity Label-MS), TMEM115 (Two-hybrid), TMEM115 (Two-hybrid), TMEM115 (Two-hybrid)

ESM2 similar proteins: A4FUB8, E9QBI7, O35394, O95070, O97681, P15920, P58872, P58873, Q0DWA9, Q0P5E4, Q12270, Q12893, Q13488, Q1RMH4, Q28C60, Q3UVK0, Q4V8F3, Q52NJ0, Q5RBS4, Q5XIT3, Q5Z413, Q6BSA9, Q6C741, Q6CDV6, Q6CR06, Q6DCK1, Q6FSG0, Q6P6G5, Q6UPR8, Q755H8, Q7Z2K6, Q874X5, Q8BHC7, Q8BXJ9, Q8RXQ2, Q8TEB9, Q8VC82, Q8VZ96, Q91VU1, Q91XB7

Diamond homologs: A4FUB8, Q12893, Q8LF05, Q9WUH1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

482 predictions. Top by Δscore:

Variant	Effect	Δscore
3:50355545:TGC:T	acceptor_gain	1.0000
3:50355545:TGCC:T	acceptor_loss	1.0000
3:50355546:GCC:G	acceptor_loss	1.0000
3:50355547:CCTGG:C	acceptor_loss	1.0000
3:50355548:C:CA	acceptor_loss	1.0000
3:50355548:C:CC	acceptor_gain	1.0000
3:50355549:T:G	acceptor_loss	1.0000
3:50355555:C:CT	acceptor_gain	1.0000
3:50355555:C:T	acceptor_gain	1.0000
3:50355556:A:T	acceptor_gain	1.0000
3:50358208:AGTAC:A	donor_loss	1.0000
3:50358209:GTACC:G	donor_loss	1.0000
3:50358210:TAC:T	donor_loss	1.0000
3:50358211:A:AG	donor_loss	1.0000
3:50358212:C:A	donor_loss	1.0000
3:50358212:CCTT:C	donor_gain	1.0000
3:50355543:GTTGC:G	acceptor_gain	0.9900
3:50355544:TTGC:T	acceptor_gain	0.9900
3:50355546:GC:G	acceptor_gain	0.9900
3:50355547:CC:C	acceptor_gain	0.9900
3:50357266:A:T	acceptor_gain	0.9900
3:50357391:C:CT	donor_gain	0.9900
3:50357392:T:TT	donor_gain	0.9900
3:50358461:A:C	donor_gain	0.9900
3:50355548:C:T	acceptor_gain	0.9800
3:50356602:C:A	donor_gain	0.9800
3:50358211:A:AC	donor_gain	0.9800
3:50358212:C:CC	donor_gain	0.9800
3:50357265:CAG:C	acceptor_gain	0.9700
3:50358376:C:CT	acceptor_gain	0.9700

AlphaMissense

2238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:50355527:A:G	L291P	0.999
3:50355527:A:T	L291H	0.999
3:50355536:A:G	L288P	0.999
3:50358255:A:G	I270T	0.999
3:50355515:A:G	L295P	0.998
3:50355539:G:T	A287D	0.998
3:50355547:C:A	R284S	0.998
3:50355547:C:G	R284S	0.998
3:50358219:C:G	R282P	0.998
3:50358255:A:T	I270N	0.998
3:50358443:G:C	F207L	0.998
3:50358443:G:T	F207L	0.998
3:50358445:A:G	F207L	0.998
3:50355542:A:G	L286P	0.997
3:50358213:C:A	R284M	0.997
3:50358213:C:G	R284T	0.997
3:50358255:A:C	I270S	0.997
3:50358461:A:C	S201R	0.997
3:50358461:A:T	S201R	0.997
3:50358463:T:G	S201R	0.997
3:50355531:C:G	A290P	0.996
3:50355540:C:T	A287T	0.996
3:50358215:T:A	R283S	0.996
3:50358215:T:G	R283S	0.996
3:50358261:A:G	I268T	0.996
3:50358886:A:G	W60R	0.996
3:50358886:A:T	W60R	0.996
3:50355518:C:G	R294P	0.995
3:50358216:C:G	R283T	0.995
3:50358460:A:G	W202R	0.995

dbSNP variants (sampled 300 via entrez): RS1000111239 (3:50359764 G>A), RS1000619900 (3:50360067 A>G), RS1001118108 (3:50361342 T>G), RS1002140246 (3:50360439 T>G), RS1002576811 (3:50355036 A>G), RS1002586670 (3:50355156 T>C), RS1003583860 (3:50356765 G>A), RS1003681720 (3:50356203 G>A,T), RS1004023337 (3:50355922 T>C), RS1004029001 (3:50356457 G>T), RS1004076448 (3:50356020 G>A), RS1004345617 (3:50359470 G>A), RS1004537271 (3:50355670 T>C), RS1004743833 (3:50359108 G>A,C), RS1005334242 (3:50360643 G>A)

Disease associations

OMIM: gene MIM:607069 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

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
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment	2
Cyclosporine	decreases methylation, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
MT19c compound	decreases 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	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Quercetin	increases phosphorylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Sodium Selenite	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C8A6	HEK293 TMEM115-3xHA GolgiTAG	Transformed cell line	Female

Clinical trials (associated diseases)

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