TMEM117

Summary

TMEM117 (transmembrane protein 117, HGNC:25308) is a protein-coding gene on chromosome 12q12, encoding Transmembrane protein 117 (Q9H0C3). Involved in endoplasmic reticulum (ER) stress-induced cell death pathway.

Involved in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Located in endoplasmic reticulum and plasma membrane.

Source: NCBI Gene 84216 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 116 total
• MANE Select transcript: NM_032256

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25308
Approved symbol	TMEM117
Name	transmembrane protein 117
Location	12q12
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434K2435
Ensembl gene	ENSG00000139173
Ensembl biotype	protein_coding
Entrez	84216

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000266534, ENST00000546387, ENST00000546868, ENST00000546978, ENST00000550495, ENST00000550623, ENST00000551577, ENST00000553253, ENST00000875244, ENST00000968375, ENST00000968376

RefSeq mRNA: 4 — MANE Select: NM_032256 NM_001286211, NM_001286212, NM_001286213, NM_032256

CCDS: CCDS73462, CCDS8745

Canonical transcript exons

ENST00000266534 — 8 exons

Exon	Start	End
ENSE00001267075	43844624	43844928
ENSE00002338108	43836081	43836196
ENSE00003540945	43944210	43944342
ENSE00003557691	44143525	44143624
ENSE00003577361	44211290	44211387
ENSE00003604545	44299580	44299739
ENSE00003646351	44388026	44389758
ENSE00003668926	44376595	44376724

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 93.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4549 / max 163.1378, expressed in 1543 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125121	5.1137	1466
125120	1.1465	706
125122	0.1794	59
125124	0.0092	4
125125	0.0060	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	93.06	silver quality
left ventricle myocardium	UBERON:0006566	92.31	silver quality
penis	UBERON:0000989	89.90	gold quality
myocardium	UBERON:0002349	87.80	silver quality
upper arm skin	UBERON:0004263	87.71	gold quality
epithelial cell of pancreas	CL:0000083	86.51	silver quality
trigeminal ganglion	UBERON:0001675	86.30	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.18	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.13	gold quality
dorsal root ganglion	UBERON:0000044	84.95	gold quality
stromal cell of endometrium	CL:0002255	84.22	gold quality
seminal vesicle	UBERON:0000998	84.05	gold quality
esophagus squamous epithelium	UBERON:0006920	83.49	gold quality
pigmented layer of retina	UBERON:0001782	83.22	gold quality
jejunal mucosa	UBERON:0000399	83.18	gold quality
gingiva	UBERON:0001828	83.06	gold quality
mammalian vulva	UBERON:0000997	83.04	gold quality
sperm	CL:0000019	82.92	silver quality
heart right ventricle	UBERON:0002080	82.83	gold quality
tibia	UBERON:0000979	82.31	gold quality
gingival epithelium	UBERON:0001949	81.53	silver quality
lower esophagus mucosa	UBERON:0035834	80.08	gold quality
esophagus mucosa	UBERON:0002469	79.65	gold quality
jejunum	UBERON:0002115	79.42	gold quality
corpus callosum	UBERON:0002336	79.38	gold quality
palpebral conjunctiva	UBERON:0001812	79.04	gold quality
amniotic fluid	UBERON:0000173	78.80	gold quality
cauda epididymis	UBERON:0004360	78.70	gold quality
duodenum	UBERON:0002114	78.50	gold quality
kidney epithelium	UBERON:0004819	78.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	54.93
E-CURD-119	yes	46.04
E-ANND-3	no	5.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting TMEM117, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-623	99.76	68.16	1170

Literature-anchored findings (GeneRIF, showing 1)

• Data suggest that transmembrane protein 117 (TMEM117) probably mediates the signalling of mitochondrial membrane potential (DeltaPsim) loss in endoplasmic reticulum (ER) stress-mediated mitochondria cell death. (PMID:28285135)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem117	ENSDARG00000088356
mus_musculus	Tmem117	ENSMUSG00000063296
rattus_norvegicus	Tmem117	ENSRNOG00000006068

Protein

Protein identifiers

Transmembrane protein 117 — Q9H0C3 (reviewed: Q9H0C3)

All UniProt accessions (4): Q9H0C3, F8VS00, F8W1J2, H0YI63

UniProt curated annotations — full annotation on UniProt →

Function. Involved in endoplasmic reticulum (ER) stress-induced cell death pathway.

Subcellular location. Cell membrane.

Similarity. Belongs to the TMEM117 family.

RefSeq proteins (4): NP_001273140, NP_001273141, NP_001273142, NP_115632* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029370	TMEM117	Family

Pfam: PF15113

UniProt features (27 total): topological domain 9, transmembrane region 8, region of interest 2, glycosylation site 2, mutagenesis site 2, chain 1, compositionally biased region 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0C3-F1	75.09	0.38

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): 453

Glycosylation sites (2): 353, 371

Mutagenesis-validated functional residues (2):

Position	Phenotype
353	reduced n-glycosylation. loss of n-glycosylation; when associated with a-371.
371	reduced n-glycosylation. loss of n-glycosylation; when associated with a-353.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, chr12q12, CTCTAGA_MIR526C_MIR518F_MIR526A, GTGCCTT_MIR506, GOBP_APOPTOTIC_SIGNALING_PATHWAY, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, ZHANG_BREAST_CANCER_PROGENITORS_UP, AML1_01, CART1_01, GTGACTT_MIR224, CTAWWWATA_RSRFC4_Q2, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS

GO Biological Process (1): intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059)

GO Molecular Function (0):

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to endoplasmic reticulum stress	1
intrinsic apoptotic signaling pathway	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM117	NELL2	Q99435	664
TMEM117	KBTBD12	Q3ZCT8	526
TMEM117	SLC2A13	Q96QE2	516
TMEM117	TMEM161B	Q8NDZ6	508
TMEM117	ZCRB1	Q8TBF4	504
TMEM117	NAALADL2	Q58DX5	460
TMEM117	SCAF11	Q99590	455
TMEM117	GXYLT1	Q4G148	454
TMEM117	USP17L7	P0C7H9	445
TMEM117	PIP5KL1	Q5T9C9	441
TMEM117	UNC79	Q9P2D8	438
TMEM117	ANO6	Q4KMQ2	437
TMEM117	TMEM11	P17152	436
TMEM117	PUS7L	Q9H0K6	419
TMEM117	CWC22	Q9HCG8	411

IntAct

0 interactions, top by confidence:

BioGRID (7): TMEM117 (Affinity Capture-MS), TMEM117 (Co-fractionation), TMEM117 (Co-fractionation), TMEM117 (Co-fractionation), TSPAN14 (Co-fractionation), UFL1 (Co-fractionation), TMEM117 (Affinity Capture-RNA)

ESM2 similar proteins: A0JPH4, A2AHL1, A8DZH4, D3ZWZ9, E7FFT2, F1QFU0, F1QZE9, P48763, P50482, P86044, Q28CV2, Q32NZ6, Q3TPR7, Q3ZAS0, Q4R7U0, Q4V8U5, Q5F3F5, Q5M7W4, Q5RH73, Q5YCC5, Q5ZKN3, Q68DH5, Q6GQE1, Q6P4P2, Q6UXY8, Q7L1W4, Q7Z2W7, Q7Z402, Q7ZYA0, Q810F5, Q8BH79, Q8C428, Q8C561, Q8CB19, Q8IZK6, Q8N3S3, Q8R455, Q8R4D5, Q8R4P4, Q8R4P5

Diamond homologs: Q7ZVW1, Q8BH18, Q9H0C3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3978 predictions. Top by Δscore:

Variant	Effect	Δscore
12:43844619:TACAG:T	acceptor_loss	1.0000
12:43844620:ACAGG:A	acceptor_loss	1.0000
12:43844621:CA:C	acceptor_loss	1.0000
12:43844622:A:AG	acceptor_gain	1.0000
12:43844622:A:C	acceptor_loss	1.0000
12:43844623:G:GG	acceptor_gain	1.0000
12:43944209:GGTCA:G	acceptor_gain	1.0000
12:43946487:GCAA:G	donor_gain	1.0000
12:43946490:A:AG	donor_gain	1.0000
12:44299575:TACA:T	acceptor_loss	1.0000
12:44299578:A:C	acceptor_loss	1.0000
12:44299579:GGACA:G	acceptor_gain	1.0000
12:44299736:GCAG:G	donor_gain	1.0000
12:44299737:CAGGT:C	donor_loss	1.0000
12:44299738:AGG:A	donor_loss	1.0000
12:44299741:T:G	donor_loss	1.0000
12:44376589:T:A	acceptor_gain	1.0000
12:44376592:CAGGA:C	acceptor_loss	1.0000
12:44376594:G:GT	acceptor_gain	1.0000
12:44376594:G:T	acceptor_loss	1.0000
12:44376594:GGAC:G	acceptor_gain	1.0000
12:44376594:GGACT:G	acceptor_gain	1.0000
12:44376720:AACAG:A	donor_loss	1.0000
12:44376722:CAGG:C	donor_loss	1.0000
12:44376723:AGGT:A	donor_loss	1.0000
12:44376724:GG:G	donor_loss	1.0000
12:44376725:GT:G	donor_loss	1.0000
12:44376726:T:G	donor_loss	1.0000
12:44388021:TGCAG:T	acceptor_loss	1.0000
12:44388022:GCAGG:G	acceptor_loss	1.0000

AlphaMissense

3460 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:44143595:T:A	W161R	1.000
12:44143595:T:C	W161R	1.000
12:44388071:A:C	D315A	1.000
12:44388071:A:T	D315V	1.000
12:44388074:T:C	L316P	1.000
12:43844729:C:A	N26K	0.999
12:43844729:C:G	N26K	0.999
12:43844748:G:C	D33H	0.999
12:43944272:A:C	S114R	0.999
12:43944274:C:A	S114R	0.999
12:43944274:C:G	S114R	0.999
12:44143581:C:A	A156D	0.999
12:44143601:G:A	G163R	0.999
12:44143601:G:C	G163R	0.999
12:44143602:G:A	G163E	0.999
12:44143604:G:C	D164H	0.999
12:44299641:T:A	W224R	0.999
12:44299641:T:C	W224R	0.999
12:44299687:G:C	R239T	0.999
12:44299688:A:C	R239S	0.999
12:44299688:A:T	R239S	0.999
12:44299720:A:C	D250A	0.999
12:44299723:T:C	L251P	0.999
12:44376604:T:C	F260L	0.999
12:44376606:C:A	F260L	0.999
12:44376606:C:G	F260L	0.999
12:44388031:T:A	W302R	0.999
12:44388031:T:C	W302R	0.999
12:44388070:G:C	D315H	0.999
12:44388071:A:G	D315G	0.999

dbSNP variants (sampled 300 via entrez): RS1000016031 (12:44194105 A>T), RS1000020414 (12:43851996 T>C), RS1000027186 (12:44176963 T>C), RS1000030421 (12:44197802 T>C), RS1000030447 (12:44069262 G>A), RS1000035531 (12:44325840 A>G), RS1000035830 (12:44168647 A>G), RS1000038260 (12:43874423 G>A,C), RS1000042265 (12:44005285 C>T), RS1000043177 (12:44373088 G>A), RS1000047490 (12:44027742 G>A), RS1000049908 (12:43956894 G>A), RS1000053888 (12:43997894 G>T), RS1000062784 (12:43937328 G>A), RS1000068555 (12:43913938 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003602_9	Inflammatory bowel disease	6.000000e-06
GCST006138_33	Resting-state electroencephalogram vigilance	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement

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
Benzo(a)pyrene	decreases expression, increases methylation, increases mutagenesis, affects expression, affects methylation	9
Aflatoxin B1	affects expression, decreases expression, decreases methylation, increases methylation	6
Valproic Acid	increases expression, decreases expression, affects cotreatment	4
Tretinoin	decreases expression, increases expression	3
sodium arsenite	increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
3,4-dichloroaniline	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression	1
NSC 689534	affects binding, decreases expression	1
trametinib	affects cotreatment, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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