TM4SF18

Summary

TM4SF18 (transmembrane 4 L six family member 18, HGNC:25181) is a protein-coding gene on chromosome 3q25.1, encoding Transmembrane 4 L6 family member 18 (Q96CE8).

Predicted to be active in membrane.

Source: NCBI Gene 116441 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_138786

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25181
Approved symbol	TM4SF18
Name	transmembrane 4 L six family member 18
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Aliases	L6D
Ensembl gene	ENSG00000163762
Ensembl biotype	protein_coding
Entrez	116441

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 retained_intron

ENST00000296059, ENST00000468398, ENST00000470080, ENST00000474754, ENST00000491182, ENST00000855969, ENST00000855970, ENST00000920885, ENST00000920886, ENST00000948535

RefSeq mRNA: 2 — MANE Select: NM_138786 NM_001184723, NM_138786

CCDS: CCDS3142

Canonical transcript exons

ENST00000296059 — 6 exons

Exon	Start	End
ENSE00001078031	149324880	149325022
ENSE00001078032	149322256	149322436
ENSE00001244455	149318498	149321492
ENSE00001819527	149333513	149333636
ENSE00003501479	149333206	149333399
ENSE00003577572	149330330	149330419

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 89.30.

FANTOM5 (CAGE): breadth broad, TPM avg 6.6962 / max 353.9141, expressed in 532 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45010	2.1322	389
45011	1.6025	357
45009	1.3971	323
45012	1.1035	295
45008	0.4609	164

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
visceral pleura	UBERON:0002401	89.30	gold quality
parietal pleura	UBERON:0002400	89.12	gold quality
metanephros cortex	UBERON:0010533	88.50	gold quality
metanephros	UBERON:0000081	87.96	gold quality
spleen	UBERON:0002106	86.24	gold quality
omental fat pad	UBERON:0010414	86.00	gold quality
peritoneum	UBERON:0002358	85.95	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.93	gold quality
thoracic mammary gland	UBERON:0005200	84.93	gold quality
mammary gland	UBERON:0001911	84.83	gold quality
smooth muscle tissue	UBERON:0001135	84.26	gold quality
adipose tissue	UBERON:0001013	83.56	gold quality
pigmented layer of retina	UBERON:0001782	83.19	gold quality
kidney epithelium	UBERON:0004819	82.87	gold quality
endothelial cell	CL:0000115	82.65	gold quality
gall bladder	UBERON:0002110	82.46	gold quality
tibialis anterior	UBERON:0001385	82.25	silver quality
cortex of kidney	UBERON:0001225	81.98	gold quality
subcutaneous adipose tissue	UBERON:0002190	81.97	gold quality
epithelium of mammary gland	UBERON:0003244	81.91	gold quality
mammary duct	UBERON:0001765	81.80	gold quality
kidney	UBERON:0002113	81.74	gold quality
adrenal tissue	UBERON:0018303	81.66	gold quality
right lobe of thyroid gland	UBERON:0001119	81.07	gold quality
islet of Langerhans	UBERON:0000006	80.75	gold quality
adult mammalian kidney	UBERON:0000082	80.45	gold quality
epithelial cell of pancreas	CL:0000083	80.10	gold quality
myocardium	UBERON:0002349	79.63	silver quality
thyroid gland	UBERON:0002046	79.41	gold quality
left lobe of thyroid gland	UBERON:0001120	79.28	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-8271	yes	522.74
E-GEOD-135922	yes	344.23
E-GEOD-134144	yes	45.14
E-HCAD-11	yes	41.98
E-HCAD-10	yes	40.32
E-MTAB-8410	yes	25.17
E-HCAD-1	yes	20.07
E-MTAB-6701	yes	15.60
E-HCAD-9	yes	15.21
E-MTAB-10553	yes	6.67
E-MTAB-5061	yes	5.96
E-GEOD-130148	yes	5.02
E-MTAB-6058	no	10.28
E-MTAB-6678	no	3.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting TM4SF18, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-576-5P	99.84	70.46	2582

Literature-anchored findings (GeneRIF, showing 2)

• TM4SF18 is highly expressed in pancreatic ductal adenocarcinoma (PDAC) tumor epithelium, expressed in normal acinar tissue and weakly expressed in normal ducts. Although there is minimal expression in normal ducts, study observed increased TM4SF18 levels in preneoplastic ducts and tumor epithelium. Knockdown of the TM4SF18 protein led to a significant decrease in Capan-1 cell growth. (PMID:30897168)
• Immune-related gene TM4SF18 could promote the metastasis of gastric cancer cells and predict the prognosis of gastric cancer patients. (PMID:36209368)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	tm4sf18	ENSDARG00000060668

Paralogs (5): TM4SF5 (ENSG00000142484), TM4SF19 (ENSG00000145107), TM4SF20 (ENSG00000168955), TM4SF4 (ENSG00000169903), TM4SF1 (ENSG00000169908)

Protein

Protein identifiers

Transmembrane 4 L6 family member 18 — Q96CE8 (reviewed: Q96CE8)

All UniProt accessions (2): C9J6Q4, Q96CE8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the L6 tetraspanin family.

RefSeq proteins (2): NP_001171652, NP_620141* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008661	L6_membrane	Family

Pfam: PF05805

UniProt features (10 total): topological domain 5, transmembrane region 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CE8-F1	79.51	0.31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): KOYAMA_SEMA3B_TARGETS_UP, chr3q25, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, HDAC4_TARGET_GENES, MIR1250_3P, MIR6833_3P, MIR4768_5P, MIR3180_5P, MIR3160_5P, MIR4760_5P, MIR4724_5P, MIR409_3P, MIR7974, MIR6888_5P, MIR3927_5P

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TM4SF18	TM4SF20	Q53R12	608
TM4SF18	TSPAN1	O60635	505
TM4SF18	TSACC	Q96A04	450
TM4SF18	TMCO5A	Q8N6Q1	385
TM4SF18	NUP210L	Q5VU65	356
TM4SF18	TOMM20L	Q6UXN7	346
TM4SF18	TMEM121	Q9BTD3	346
TM4SF18	ENTREP2	O60320	331
TM4SF18	AK8	Q96MA6	323
TM4SF18	TCP10L	Q8TDR4	316
TM4SF18	NUDT13	Q86X67	312
TM4SF18	ANKRD7	Q92527	311
TM4SF18	ENTREP3	P81408	299
TM4SF18	TMSB15A	P0CG34	294
TM4SF18	ENTREP1	Q15884	290

IntAct

109 interactions, top by confidence:

A	B	Type	Score
MIP	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
FAM3C	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
PMP22	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	UBE2J1	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	MS4A3	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	GIMAP5	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
EMP3	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
NIPAL4	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
CLDN19	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	FXYD6	psi-mi:“MI:0915”(physical association)	0.560
LAT	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	TREX1	psi-mi:“MI:0915”(physical association)	0.560
CYB561	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
TMEM218	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
ITGB2	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	RPRM	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	IER3IP1	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	TEX264	psi-mi:“MI:0915”(physical association)	0.560
MAL	TM4SF18	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	SLC39A9	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	UNC93B1	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	SMIM3	psi-mi:“MI:0915”(physical association)	0.560
TM4SF18	CLEC2D	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (51): TMEM65 (Affinity Capture-MS), CD320 (Affinity Capture-MS), STXBP1 (Affinity Capture-MS), TMEM179B (Affinity Capture-MS), CD47 (Affinity Capture-MS), REEP5 (Affinity Capture-MS), TM4SF18 (Two-hybrid), TM4SF18 (Two-hybrid), TM4SF18 (Two-hybrid), TM4SF18 (Two-hybrid), TM4SF18 (Two-hybrid), TM4SF18 (Two-hybrid), TM4SF18 (Two-hybrid), TM4SF18 (Two-hybrid), TM4SF18 (Two-hybrid)

ESM2 similar proteins: A2VDC7, A4FUZ5, A9CAZ8, B9TRX0, O15243, O89013, O95807, P04116, P23289, P23294, P36963, P36965, P47789, P47790, P56557, P60201, P60202, P60203, Q0P442, Q0P467, Q13491, Q13530, Q1E1E0, Q3SYT0, Q3SZL9, Q3T110, Q3ZC23, Q4R6L9, Q561T9, Q566G2, Q5PSV5, Q5R4C3, Q5R533, Q5R603, Q5R6E6, Q5ZJD9, Q712P7, Q7TNK0, Q7Z0Q2, Q803X0

Diamond homologs: E9Q9H8, O14894, P30408, P48230, P49111, Q2KIG8, Q3T110, Q53R12, Q5R6Z4, Q5RE43, Q64302, Q91XD3, Q96CE8, Q96DZ7, Q9CQY8, Q9EQL5, Q3T0Z4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

730 predictions. Top by Δscore:

Variant	Effect	Δscore
3:149333202:TTA:T	donor_loss	1.0000
3:149333203:TA:T	donor_loss	1.0000
3:149333204:A:AC	donor_gain	1.0000
3:149333204:ACCAT:A	donor_loss	1.0000
3:149333205:C:CC	donor_gain	1.0000
3:149324992:C:CT	acceptor_gain	0.9900
3:149324993:G:T	acceptor_gain	0.9900
3:149325023:C:CC	acceptor_gain	0.9900
3:149330329:CCA:C	donor_gain	0.9900
3:149330418:ATC:A	acceptor_loss	0.9900
3:149330419:TCTA:T	acceptor_loss	0.9900
3:149330420:C:CA	acceptor_loss	0.9900
3:149333200:ACTT:A	donor_loss	0.9900
3:149333204:AC:A	donor_gain	0.9900
3:149333205:CC:C	donor_gain	0.9900
3:149333205:CCA:C	donor_gain	0.9900
3:149333205:CCAT:C	donor_gain	0.9900
3:149333205:CCATG:C	donor_gain	0.9900
3:149333512:CCA:C	donor_gain	0.9800
3:149324992:C:T	acceptor_gain	0.9700
3:149330420:C:CC	acceptor_gain	0.9700
3:149324878:A:AC	donor_gain	0.9600
3:149324879:C:CC	donor_gain	0.9600
3:149324908:C:CA	donor_gain	0.9600
3:149324978:A:T	acceptor_gain	0.9600
3:149330417:CAT:C	acceptor_gain	0.9600
3:149333200:A:AC	donor_gain	0.9500
3:149333201:C:CC	donor_gain	0.9500
3:149333517:T:TA	donor_gain	0.9500
3:149324874:CCTTA:C	donor_loss	0.9400

AlphaMissense

1304 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:149324909:C:A	W127C	0.985
3:149324909:C:G	W127C	0.985
3:149322340:A:C	S169R	0.982
3:149322340:A:T	S169R	0.982
3:149322342:T:G	S169R	0.982
3:149333320:A:C	S21R	0.982
3:149333320:A:T	S21R	0.982
3:149333322:T:G	S21R	0.982
3:149322404:C:G	C148S	0.973
3:149322405:A:T	C148S	0.973
3:149324911:A:G	W127R	0.967
3:149324911:A:T	W127R	0.967
3:149322405:A:G	C148R	0.965
3:149333308:G:C	N25K	0.964
3:149333308:G:T	N25K	0.964
3:149322403:G:C	C148W	0.963
3:149324927:G:C	C121W	0.963
3:149324928:C:G	C121S	0.962
3:149324929:A:T	C121S	0.962
3:149322378:A:G	W157R	0.961
3:149322378:A:T	W157R	0.961
3:149333325:A:G	W20R	0.961
3:149333325:A:T	W20R	0.961
3:149333229:C:G	G52R	0.959
3:149333229:C:T	G52R	0.959
3:149322376:C:A	W157C	0.957
3:149322376:C:G	W157C	0.957
3:149324897:A:C	F131L	0.957
3:149324897:A:T	F131L	0.957
3:149324899:A:G	F131L	0.957

dbSNP variants (sampled 300 via entrez): RS1000347524 (3:149330150 G>A,C), RS1000611961 (3:149334697 C>T), RS1000681224 (3:149331771 A>G), RS1000903856 (3:149319495 C>T), RS1001093406 (3:149327558 T>G), RS1001283740 (3:149331599 C>T), RS1001388078 (3:149325952 CTGTG>C,CTG), RS1001622883 (3:149324802 A>G), RS1001632568 (3:149318521 T>C), RS1001716733 (3:149331230 T>C), RS1001758788 (3:149325104 C>A,T), RS1001918776 (3:149319755 A>G), RS1001978448 (3:149318245 C>G), RS1002095923 (3:149326289 C>A,G), RS1002144878 (3:149331307 G>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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
methylparaben	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
mercuric bromide	affects cotreatment, increases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Dihydrotestosterone	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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