TMEM45B

Summary

TMEM45B (transmembrane protein 45B, HGNC:25194) is a protein-coding gene on chromosome 11q24.3, encoding Transmembrane protein 45B (Q96B21). Plays a role in innate immunity.

Predicted to be involved in innate immune response. Predicted to be located in Golgi apparatus; endosome membrane; and lysosomal membrane.

Source: NCBI Gene 120224 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_138788

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25194
Approved symbol	TMEM45B
Name	transmembrane protein 45B
Location	11q24.3
Locus type	gene with protein product
Status	Approved
Aliases	BC016153, FLJ40787
Ensembl gene	ENSG00000151715
Ensembl biotype	protein_coding
OMIM	621075
Entrez	120224

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 30 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000281441, ENST00000524567, ENST00000525709, ENST00000527754, ENST00000529381, ENST00000887357, ENST00000887358, ENST00000887359, ENST00000887360, ENST00000887361, ENST00000887362, ENST00000887363, ENST00000887364, ENST00000887365, ENST00000887366, ENST00000887367, ENST00000887368, ENST00000887369, ENST00000887370, ENST00000887371, ENST00000887372, ENST00000887373, ENST00000887374, ENST00000887375, ENST00000887376, ENST00000944775, ENST00000944776, ENST00000944777, ENST00000944778, ENST00000944779, ENST00000944780, ENST00000944781, ENST00000944782

RefSeq mRNA: 4 — MANE Select: NM_138788 NM_001331210, NM_001331211, NM_001331212, NM_138788

CCDS: CCDS8482

Canonical transcript exons

ENST00000281441 — 6 exons

Exon	Start	End
ENSE00001001316	129857313	129857458
ENSE00001282227	129858574	129860003
ENSE00002154634	129815848	129815898
ENSE00003578939	129852475	129852660
ENSE00003635159	129855708	129855892
ENSE00003686220	129854610	129854816

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 4.4235 / max 328.9459, expressed in 469 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117587	4.1655	442
117586	0.2341	122
117588	0.0111	3
117589	0.0095	3
117590	0.0034	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.50	gold quality
jejunal mucosa	UBERON:0000399	98.52	gold quality
mucosa of transverse colon	UBERON:0004991	98.16	gold quality
rectum	UBERON:0001052	98.08	gold quality
colonic mucosa	UBERON:0000317	97.95	gold quality
lower esophagus mucosa	UBERON:0035834	97.86	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.58	gold quality
duodenum	UBERON:0002114	96.21	gold quality
bronchial epithelial cell	CL:0002328	95.43	gold quality
nasal cavity epithelium	UBERON:0005384	95.30	gold quality
upper arm skin	UBERON:0004263	95.24	silver quality
bronchus	UBERON:0002185	94.89	gold quality
esophagus mucosa	UBERON:0002469	94.76	gold quality
epithelial cell of pancreas	CL:0000083	94.57	gold quality
gingival epithelium	UBERON:0001949	94.52	gold quality
gingiva	UBERON:0001828	94.18	gold quality
esophagus squamous epithelium	UBERON:0006920	92.91	gold quality
islet of Langerhans	UBERON:0000006	92.85	gold quality
epithelium of nasopharynx	UBERON:0001951	91.07	gold quality
nasopharynx	UBERON:0001728	91.05	gold quality
oral cavity	UBERON:0000167	90.87	gold quality
pharyngeal mucosa	UBERON:0000355	90.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.58	gold quality
gall bladder	UBERON:0002110	90.09	gold quality
penis	UBERON:0000989	89.77	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.62	gold quality
small intestine	UBERON:0002108	89.03	gold quality
right uterine tube	UBERON:0001302	89.02	gold quality
transverse colon	UBERON:0001157	89.01	gold quality
amniotic fluid	UBERON:0000173	88.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	285.94
E-HCAD-10	yes	23.08
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting TMEM45B, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-376B-5P	98.46	66.40	606

Literature-anchored findings (GeneRIF, showing 6)

• TMEM45B expression was significantly upregulated in pancreatic cancer tissues and cell lines. Moreover, TMEM45B was significantly positively correlated with the cell cycle and metastasis up pathways and regulated expression of proteins involved. This indicates an important role of TMEM45B in pancreatic cancer carcinogenesis. (PMID:27108650)
• Data show that transmembrane protein 45B (TMEM45B) was overexpressed in lung cancer and its expression correlated with overall survival of patients. (PMID:27225290)
• TMEM45B plays an important role in regulating the proliferation, migration, and invasion of osteosarcoma cells. (PMID:28244852)
• TMEM45B may be a new potent therapeutic molecule for the treatment of gastric cancer. (PMID:29803169)
• increased expression of TMEM45B appears to be significantly associated with prostate carcinoma progression and metastasis (PMID:30249106)
• TMEMu45B Interacts with Sindbis Virus Nsp1 and Nsp4 and Inhibits Viral Replication. (PMID:35938871)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem45b	ENSDARG00000056239
mus_musculus	Tmem45b	ENSMUSG00000041737
rattus_norvegicus	Tmem45b	ENSRNOG00000008515

Paralogs (2): TMEM45A (ENSG00000181458), TEDDM1 (ENSG00000203730)

Protein

Protein identifiers

Transmembrane protein 45B — Q96B21 (reviewed: Q96B21)

All UniProt accessions (1): Q96B21

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in innate immunity. Mechanistically, promotes alphaviruses RNA degradation by interacting with the viral polymerase nsP4 and the mRNA-capping enzyme nsP1 and thereby interfering with the interaction between viral RNA and nsP1. Essential for inflammation- and tissue injury-induced mechanical pain hypersensitivity.

Subunit / interactions. (Microbial infection) Interacts with sindbis virus nsP1 and nsP4; these interactions lead to viral RNA replication inhibition. (Microbial infection) Interacts with chikungunya virus nsP1 and nsP4; these interactions lead to viral RNA replication inhibition.

Subcellular location. Endosome membrane. Lysosome membrane. Golgi apparatus. trans-Golgi network membrane.

Induction. By type I interferons.

Similarity. Belongs to the TMEM45 family.

RefSeq proteins (4): NP_001318139, NP_001318140, NP_001318141, NP_620143* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006904	DUF716	Family
IPR042127	TMEM45	Family

Pfam: PF04819

UniProt features (11 total): transmembrane region 7, modified residue 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96B21-F1	90.90	0.75

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 (2): 270, 272

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 112 (showing top): GOCC_VACUOLAR_MEMBRANE, GOZGIT_ESR1_TARGETS_DN, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, PATIL_LIVER_CANCER, BILD_HRAS_ONCOGENIC_SIGNATURE, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, MODULE_205, GOCC_TRANS_GOLGI_NETWORK, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_RESPONSE_TO_PAIN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5

GO Biological Process (3): innate immune response (GO:0045087), response to pain (GO:0048265), immune system process (GO:0002376)

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

GO Cellular Component (7): lysosomal membrane (GO:0005765), trans-Golgi network (GO:0005802), endosome membrane (GO:0010008), lysosome (GO:0005764), endosome (GO:0005768), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
immune response	1
defense response to symbiont	1
multicellular organismal response to stress	1
biological_process	1
binding	1
lysosome	1
lytic vacuole membrane	1
Golgi apparatus subcompartment	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
lytic vacuole	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM45B	SH2D7	A6NKC9	542
TMEM45B	UBE2G2	P56554	470
TMEM45B	TMEM61	Q8N0U2	434
TMEM45B	GPR160	Q9UJ42	418
TMEM45B	PDCL2	Q8N4E4	415
TMEM45B	POPDC1	Q8NE79	406
TMEM45B	TMEM213	A2RRL7	398
TMEM45B	TMEM25	Q86YD3	387
TMEM45B	LRRN4CL	Q8ND94	385
TMEM45B	SAPCD2	Q86UD0	384
TMEM45B	TMEM116	Q8NCL8	380
TMEM45B	ENDOU	P21128	379
TMEM45B	TMEM233	B4DJY2	371
TMEM45B	IGSF9B	Q9UPX0	370
TMEM45B	KRT23	Q9C075	367

IntAct

118 interactions, top by confidence:

A	B	Type	Score
TMEM218	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
SEC23A	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
PLP1	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TSPAN33	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TTMP	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TMEM128	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF10C	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
PLN	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
CDS2	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TMEM45B	TMEM243	psi-mi:“MI:0915”(physical association)	0.560
SMIM1	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TMEM254	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TMEM45B	APOL2	psi-mi:“MI:0915”(physical association)	0.560
ARLN	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
SMAGP	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TMEM45B	INSIG2	psi-mi:“MI:0915”(physical association)	0.560
ANKRD46	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
APOD	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TMEM45B	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
CYB561D2	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
CACNG1	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
GIMAP1	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
AQP1	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
TMEM45B	DOLK	psi-mi:“MI:0915”(physical association)	0.560
SYNGR1	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
FAM3C	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (46): TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid), TMEM45B (Two-hybrid)

ESM2 similar proteins: A3A9H6, A3KPR5, A5D9A7, C4IYS8, P0AEL1, P10897, P34465, P49447, Q04453, Q0WRW8, Q2Y9R4, Q3T130, Q497B2, Q4V8K1, Q503V1, Q53TN4, Q5CZL8, Q5RAJ4, Q5RCZ2, Q5RKJ2, Q5U2W7, Q5XGD7, Q60720, Q67ZF6, Q687X5, Q6DDR3, Q6I681, Q6INU7, Q6NS09, Q6P1H1, Q7XMK3, Q8L856, Q8NBI2, Q8VCZ2, Q8VYH6, Q91577, Q923B6, Q925G2, Q93ZH9, Q95204

Diamond homologs: Q3T130, Q497B2, Q5T9Z0, Q5XGD7, Q60774, Q6NS09, Q6P0S3, Q8VCZ2, Q96B21, Q9NWC5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1475 predictions. Top by Δscore:

Variant	Effect	Δscore
11:129852471:TTA:T	acceptor_loss	1.0000
11:129852473:AGG:A	acceptor_loss	1.0000
11:129852474:GGT:G	acceptor_gain	1.0000
11:129852657:ACTGG:A	donor_loss	1.0000
11:129852659:TGGT:T	donor_loss	1.0000
11:129852660:GGT:G	donor_loss	1.0000
11:129852661:GTA:G	donor_loss	1.0000
11:129852662:T:A	donor_loss	1.0000
11:129857311:A:AG	acceptor_gain	1.0000
11:129857312:G:GG	acceptor_gain	1.0000
11:129857312:GATT:G	acceptor_gain	1.0000
11:129857459:G:GA	donor_loss	1.0000
11:129857460:T:A	donor_loss	1.0000
11:129858571:A:G	acceptor_gain	1.0000
11:129815949:G:GT	donor_gain	0.9900
11:129815990:G:GT	donor_gain	0.9900
11:129852473:A:AG	acceptor_gain	0.9900
11:129852473:AG:A	acceptor_gain	0.9900
11:129852474:G:GA	acceptor_gain	0.9900
11:129852474:GG:G	acceptor_gain	0.9900
11:129852641:G:GT	donor_gain	0.9900
11:129852661:G:GG	donor_gain	0.9900
11:129854681:T:G	donor_gain	0.9900
11:129854730:G:GT	donor_gain	0.9900
11:129855876:G:T	donor_gain	0.9900
11:129857307:CCCTA:C	acceptor_loss	0.9900
11:129857308:CCTA:C	acceptor_loss	0.9900
11:129857309:CTAGA:C	acceptor_loss	0.9900
11:129857310:TAG:T	acceptor_loss	0.9900
11:129857311:AGA:A	acceptor_loss	0.9900

AlphaMissense

1815 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:129852516:A:C	S12R	0.994
11:129852518:T:A	S12R	0.994
11:129852518:T:G	S12R	0.994
11:129855857:A:C	S179R	0.993
11:129855859:T:A	S179R	0.993
11:129855859:T:G	S179R	0.993
11:129855881:T:A	W187R	0.993
11:129855881:T:C	W187R	0.993
11:129857354:G:C	W204C	0.990
11:129857354:G:T	W204C	0.990
11:129852513:G:T	G11W	0.989
11:129857352:T:A	W204R	0.988
11:129857352:T:C	W204R	0.988
11:129855875:G:A	G185R	0.987
11:129855875:G:C	G185R	0.987
11:129857403:T:A	W221R	0.986
11:129857403:T:C	W221R	0.986
11:129852514:G:A	G11E	0.985
11:129854690:T:A	W87R	0.984
11:129854690:T:C	W87R	0.984
11:129857328:T:C	F196L	0.984
11:129857330:C:A	F196L	0.984
11:129857330:C:G	F196L	0.984
11:129852534:G:A	G18R	0.982
11:129852534:G:C	G18R	0.982
11:129855852:G:C	R177P	0.981
11:129855800:A:C	S160R	0.980
11:129855802:T:A	S160R	0.980
11:129855802:T:G	S160R	0.980
11:129855876:G:A	G185E	0.980

dbSNP variants (sampled 300 via entrez): RS1000057972 (11:129830713 T>C), RS1000071978 (11:129837582 G>A,C), RS1000202642 (11:129859387 A>T), RS1000225718 (11:129843886 A>C), RS1000257925 (11:129856360 C>A,T), RS1000279311 (11:129844875 T>C), RS1000349073 (11:129849426 A>G), RS1000351517 (11:129824932 A>G), RS1000400474 (11:129837290 CTTTTT>C,CTT,CTTTT,CTTTTTT), RS1000481145 (11:129851401 A>G), RS1000496200 (11:129841929 TAAAAG>T), RS1000590952 (11:129855310 G>A), RS1000622122 (11:129855077 C>G,T), RS1000829472 (11:129849700 C>T), RS1000879653 (11:129853867 C>G)

Disease associations

OMIM: gene MIM:621075 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001369_3	Type 2 diabetes	3.000000e-07
GCST001420_3	Breast cancer	5.000000e-07
GCST001762_103	Obesity-related traits	7.000000e-06
GCST003542_66	Night sleep phenotypes	1.000000e-06
GCST008180_7	Spontaneous preterm birth with premature rupture of membranes	5.000000e-06
GCST012020_139	Serum metabolite levels	2.000000e-12
GCST012194_6	Obsessive-compulsive traits	3.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight
EFO:0007827	nighttime rest measurement
EFO:0006917	spontaneous preterm birth

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, decreases reaction, affects cotreatment, increases expression	5
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	4
Particulate Matter	increases abundance, increases expression	3
bisphenol A	affects expression, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Smoke	increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
chloroacetaldehyde	decreases expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
sodium arsenite	increases expression	1
tobacco tar	decreases reaction, increases expression	1
benzo(e)pyrene	decreases methylation	1
diallyl disulfide	decreases reaction, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
hydroquinone	increases expression	1
casticin	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
ormosil	decreases expression, affects binding	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Cidofovir	decreases expression	1
Caffeine	affects phosphorylation	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	decreases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Clodronic Acid	decreases expression	1

Clinical trials (associated diseases)

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