TMEM116

Summary

TMEM116 (transmembrane protein 116, HGNC:25084) is a protein-coding gene on chromosome 12q24.13, encoding Transmembrane protein 116 (Q8NCL8).

Predicted to be involved in signal transduction. Predicted to be located in membrane.

Source: NCBI Gene 89894 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_001193531

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25084
Approved symbol	TMEM116
Name	transmembrane protein 116
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90167
Ensembl gene	ENSG00000198270
Ensembl biotype	protein_coding
Entrez	89894

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 24 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000355445, ENST00000437003, ENST00000546537, ENST00000546962, ENST00000547878, ENST00000548283, ENST00000549425, ENST00000549537, ENST00000550020, ENST00000550037, ENST00000550233, ENST00000550800, ENST00000550831, ENST00000551297, ENST00000552374, ENST00000552800, ENST00000552801, ENST00000552839, ENST00000716727, ENST00000716768, ENST00000718450, ENST00000880135, ENST00000880136, ENST00000880137, ENST00000880138, ENST00000880139, ENST00000880140, ENST00000880141, ENST00000880142, ENST00000880143, ENST00000880144, ENST00000880145, ENST00000880146, ENST00000932745, ENST00000963792

RefSeq mRNA: 4 — MANE Select: NM_001193531 NM_001193453, NM_001193531, NM_001294314, NM_138341

CCDS: CCDS55886, CCDS55887, CCDS9157

Canonical transcript exons

ENST00000552374 — 11 exons

Exon	Start	End
ENSE00003282341	112013002	112013165
ENSE00003459804	111937160	111937243
ENSE00003494927	111932586	111932659
ENSE00003498194	111943265	111943369
ENSE00003500665	112003800	112003863
ENSE00003545164	111938161	111938210
ENSE00003632316	111933886	111934030
ENSE00003694232	111991758	111991889
ENSE00003785637	111936692	111936830
ENSE00004030412	112005257	112005303
ENSE00004030414	111931298	111931827

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 91.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3468 / max 143.1427, expressed in 1703 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133319	8.2634	1694
133318	0.5117	149
133317	0.3423	106
133320	0.1989	79
133321	0.0303	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	91.72	gold quality
nasal cavity epithelium	UBERON:0005384	91.32	gold quality
heart left ventricle	UBERON:0002084	90.34	gold quality
heart right ventricle	UBERON:0002080	90.27	gold quality
cardiac ventricle	UBERON:0002082	90.21	gold quality
apex of heart	UBERON:0002098	90.13	gold quality
metanephros cortex	UBERON:0010533	89.90	gold quality
adult mammalian kidney	UBERON:0000082	89.83	gold quality
calcaneal tendon	UBERON:0003701	89.78	gold quality
left testis	UBERON:0004533	88.18	gold quality
right testis	UBERON:0004534	87.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.67	gold quality
testis	UBERON:0000473	87.42	gold quality
cortex of kidney	UBERON:0001225	87.36	gold quality
bronchial epithelial cell	CL:0002328	87.17	gold quality
kidney epithelium	UBERON:0004819	87.14	gold quality
kidney	UBERON:0002113	86.84	gold quality
heart	UBERON:0000948	86.60	gold quality
bronchus	UBERON:0002185	86.35	gold quality
renal medulla	UBERON:0000362	86.00	gold quality
nasal cavity mucosa	UBERON:0001826	85.90	gold quality
skin of leg	UBERON:0001511	85.15	gold quality
palpebral conjunctiva	UBERON:0001812	84.86	gold quality
skin of abdomen	UBERON:0001416	84.52	gold quality
ileal mucosa	UBERON:0000331	84.48	gold quality
left ventricle myocardium	UBERON:0006566	84.27	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.12	gold quality
right adrenal gland	UBERON:0001233	84.05	gold quality
zone of skin	UBERON:0000014	83.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting TMEM116, 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-5692A	100.00	74.40	6850
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-2909	96.36	67.30	562
HSA-MIR-4761-3P	96.27	66.26	524
HSA-MIR-1298-3P	94.05	64.84	620

Literature-anchored findings (GeneRIF, showing 1)

• TMEM116 is required for lung cancer cell motility and metastasis through PDK1 signaling pathway. (PMID:34789718)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem116	ENSDARG00000077155
mus_musculus	Tmem116	ENSMUSG00000029452
rattus_norvegicus	Tmem116	ENSRNOG00000027480

Paralogs (1): GPR157 (ENSG00000180758)

Protein

Protein identifiers

Transmembrane protein 116 — Q8NCL8 (reviewed: Q8NCL8)

All UniProt accessions (8): Q8NCL8, F8VNZ8, F8VP39, F8VQZ8, F8VRN7, F8VWU6, F8W1L7, G3V1Z3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Endoplasmic reticulum membrane Endoplasmic reticulum membrane.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NCL8-1	1	yes
Q8NCL8-2	2
Q8NCL8-3	3

RefSeq proteins (4): NP_001180382, NP_001180460, NP_001281243, NP_612350 (=MANE)

Domains & families (InterPro)

UniProt features (13 total): topological domain 4, transmembrane region 3, sequence conflict 2, splice variant 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCL8-F1	74.00	0.03

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 92 (showing top): AREB6_03, YGCGYRCGC_UNKNOWN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, chr12q24, THUM_SYSTOLIC_HEART_FAILURE_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, WIERENGA_STAT5A_TARGETS_UP, WIERENGA_STAT5A_TARGETS_GROUP1, SERVITJA_LIVER_HNF1A_TARGETS_UP, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, FORTSCHEGGER_PHF8_TARGETS_UP, CAMP_UP.V1_UP

GO Biological Process (2): signal transduction (GO:0007165), biological_process (GO:0008150)

GO Molecular Function (1): molecular_function (GO:0003674)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM116	NAA25	Q14CX7	649
TMEM116	ACAD10	Q6JQN1	647
TMEM116	TMEM72	A0PK05	623
TMEM116	TMEM213	A2RRL7	584
TMEM116	TMEM207	Q6UWW9	575
TMEM116	HECTD4	Q9Y4D8	544
TMEM116	TMEM25	Q86YD3	543
TMEM116	TMEM253	P0C7T8	540
TMEM116	TRAFD1	O14545	512
TMEM116	ALDH2	P05091	510
TMEM116	RTP3	Q9BQQ7	507
TMEM116	TMEM61	Q8N0U2	507
TMEM116	NDC1	Q9BTX1	505
TMEM116	ZNF704	Q6ZNC4	489
TMEM116	CWC27	Q6UX04	471

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TMEM116	NRP1	psi-mi:“MI:0915”(physical association)	0.400
TMEM116	IGHA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): TMEM116 (Synthetic Lethality), TMEM116 (Negative Genetic), NRP1 (Affinity Capture-MS), RETSAT (Affinity Capture-MS), CLCN3 (Affinity Capture-MS), IGHA1 (Affinity Capture-MS), PDZD8 (Affinity Capture-MS), LCN1 (Affinity Capture-MS)

ESM2 similar proteins: A2BGS3, A6NGA9, E7F594, O36364, O60478, O60883, O95800, O95838, P03208, P16849, P31389, P34590, P35367, P49219, Q03613, Q09351, Q09964, Q09965, Q14439, Q16950, Q16951, Q2KI97, Q3U3F9, Q5FVG1, Q5IXF8, Q5UAW9, Q60755, Q64017, Q66615, Q66H29, Q6P7G9, Q6SW98, Q6X632, Q7TSN5, Q7TSN6, Q80W35, Q80WT4, Q8BNQ3, Q8C206, Q8CIM5

Diamond homologs: A2BGS3, Q8NCL8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2504 predictions. Top by Δscore:

Variant	Effect	Δscore
12:111937244:C:CC	acceptor_gain	1.0000
12:111932743:C:CT	acceptor_gain	0.9900
12:111936759:C:CT	donor_gain	0.9900
12:111936760:T:TT	donor_gain	0.9900
12:111937158:A:AC	donor_gain	0.9900
12:111937159:C:CC	donor_gain	0.9900
12:111937239:TCAGG:T	acceptor_gain	0.9900
12:111937240:CAGG:C	acceptor_gain	0.9900
12:111937240:CAGGC:C	acceptor_gain	0.9900
12:111990718:A:AC	donor_gain	0.9900
12:111990719:C:CC	donor_gain	0.9900
12:112005250:AACAT:A	donor_loss	0.9900
12:112005251:ACAT:A	donor_loss	0.9900
12:112005252:CATA:C	donor_loss	0.9900
12:112005253:AT:A	donor_loss	0.9900
12:112005254:TA:T	donor_loss	0.9900
12:112005256:C:CT	donor_loss	0.9900
12:112005304:C:CA	acceptor_loss	0.9900
12:112005304:C:CC	acceptor_gain	0.9900
12:112013030:G:GA	donor_gain	0.9900
12:112013605:ACAAG:A	donor_loss	0.9900
12:112013606:CAAGG:C	donor_loss	0.9900
12:112013607:AAGG:A	donor_loss	0.9900
12:112013608:AG:A	donor_loss	0.9900
12:112013609:GG:G	donor_loss	0.9900
12:112013611:T:G	donor_loss	0.9900
12:111937589:T:A	donor_gain	0.9800
12:111943343:G:C	acceptor_gain	0.9800
12:111946989:A:C	acceptor_gain	0.9800
12:112005253:ATACC:A	acceptor_loss	0.9800

AlphaMissense

2188 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:111936707:G:C	S99R	0.988
12:111936707:G:T	S99R	0.988
12:111936709:T:G	S99R	0.988
12:111936719:G:C	S95R	0.983
12:111936719:G:T	S95R	0.983
12:111936721:T:G	S95R	0.983
12:111933905:G:C	F146L	0.956
12:111933905:G:T	F146L	0.956
12:111933907:A:G	F146L	0.956
12:111937243:G:C	S30R	0.954
12:111937243:G:T	S30R	0.954
12:111938162:T:G	S30R	0.954
12:111931806:C:G	G185R	0.952
12:111933901:A:G	C148R	0.950
12:111933898:A:G	C149R	0.945
12:111933892:C:G	G151R	0.941
12:111931712:A:G	L216S	0.940
12:111931795:G:C	N188K	0.935
12:111931795:G:T	N188K	0.935
12:111937188:A:G	C49R	0.934
12:111931794:A:G	C189R	0.925
12:111931699:C:A	Q220H	0.922
12:111931699:C:G	Q220H	0.922
12:111937187:C:G	C49S	0.915
12:111937188:A:T	C49S	0.915
12:111933896:G:C	C149W	0.911
12:111936716:A:C	F96L	0.911
12:111936716:A:T	F96L	0.911
12:111936718:A:G	F96L	0.911
12:111937183:G:C	F50L	0.909

dbSNP variants (sampled 300 via entrez): RS1000064098 (12:111940887 T>C), RS1000068238 (12:111911579 C>A,T), RS1000092907 (12:111962323 T>C), RS1000131772 (12:111961537 C>T), RS1000134823 (12:112009857 A>C), RS1000170946 (12:111990983 G>A), RS1000179710 (12:111980100 A>G), RS1000186867 (12:111932870 G>C), RS1000213077 (12:111990397 A>G), RS1000238300 (12:111983136 TA>T,TAA), RS1000284367 (12:111996528 C>T), RS1000285882 (12:111918224 C>T), RS1000376907 (12:111984630 A>C), RS1000461424 (12:111961154 A>G), RS1000463836 (12:111924991 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

9 associations (top):

Study	Trait	p-value
GCST004131_54	Inflammatory bowel disease	2.000000e-09
GCST004132_84	Crohn’s disease	7.000000e-07
GCST004603_120	Platelet count	4.000000e-15
GCST005951_1	Body mass index	4.000000e-12
GCST005951_75	Body mass index	2.000000e-11
GCST006231_55	Mean arterial pressure	6.000000e-09
GCST007876_6	Estimated glomerular filtration rate	2.000000e-11
GCST010083_300	Hemoglobin levels	2.000000e-53
GCST012044_4	Tea consumption	1.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004340	body mass index
EFO:0006340	mean arterial pressure
EFO:0004509	hemoglobin measurement
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Nickel	decreases expression	2
Aflatoxin B1	decreases methylation, affects expression	2
methylmercuric chloride	decreases expression	1
nobiletin	increases expression	1
arsenite	increases reaction, affects binding	1
sulforaphane	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
ICG 001	increases expression	1
jinfukang	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Phthalic Acids	decreases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1
Valproic Acid	decreases methylation, increases expression	1
Oxyquinoline	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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