TMEM45A

Summary

TMEM45A (transmembrane protein 45A, HGNC:25480) is a protein-coding gene on chromosome 3q12.2, encoding Transmembrane protein 45A (Q9NWC5).

Predicted to be located in membrane.

Source: NCBI Gene 55076 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_018004

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25480
Approved symbol	TMEM45A
Name	transmembrane protein 45A
Location	3q12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10134, DERP7
Ensembl gene	ENSG00000181458
Ensembl biotype	protein_coding
OMIM	616928
Entrez	55076

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 31 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000323523, ENST00000403410, ENST00000449609, ENST00000462884, ENST00000485260, ENST00000488904, ENST00000489060, ENST00000860730, ENST00000860731, ENST00000860732, ENST00000860733, ENST00000860734, ENST00000860735, ENST00000860736, ENST00000860737, ENST00000860738, ENST00000860739, ENST00000860740, ENST00000860741, ENST00000860742, ENST00000860743, ENST00000860744, ENST00000860745, ENST00000860746, ENST00000860747, ENST00000860748, ENST00000860749, ENST00000860750, ENST00000860751, ENST00000860752, ENST00000860753, ENST00000915410, ENST00000915411, ENST00000950666, ENST00000950667

RefSeq mRNA: 2 — MANE Select: NM_018004 NM_001363876, NM_018004

CCDS: CCDS2937, CCDS87113

Canonical transcript exons

ENST00000323523 — 6 exons

Exon	Start	End
ENSE00001226114	100558405	100558589
ENSE00001517566	100492619	100492928
ENSE00003469893	100576925	100577444
ENSE00003524166	100555209	100555401
ENSE00003542373	100556760	100556972
ENSE00003603782	100568822	100568967

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 99.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.9229 / max 847.1278, expressed in 1470 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37611	9.5580	1403
37613	3.4959	939
37616	1.7650	184
37614	1.2634	488
37612	0.3810	191
202861	0.2398	121
37615	0.1106	29
37617	0.1093	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
penis	UBERON:0000989	99.81	gold quality
mammalian vulva	UBERON:0000997	99.79	gold quality
upper leg skin	UBERON:0004262	99.76	gold quality
upper arm skin	UBERON:0004263	99.64	gold quality
skin of hip	UBERON:0001554	99.51	gold quality
skin of abdomen	UBERON:0001416	99.34	gold quality
nipple	UBERON:0002030	99.31	gold quality
decidua	UBERON:0002450	99.23	gold quality
zone of skin	UBERON:0000014	99.14	gold quality
skin of leg	UBERON:0001511	99.04	gold quality
gingival epithelium	UBERON:0001949	98.76	gold quality
gingiva	UBERON:0001828	97.89	gold quality
tongue squamous epithelium	UBERON:0006919	97.65	gold quality
cervix epithelium	UBERON:0004801	97.47	gold quality
pericardium	UBERON:0002407	97.41	gold quality
cervix squamous epithelium	UBERON:0006922	97.26	gold quality
cartilage tissue	UBERON:0002418	96.41	gold quality
bronchial epithelial cell	CL:0002328	95.72	gold quality
tibia	UBERON:0000979	95.67	gold quality
stromal cell of endometrium	CL:0002255	95.54	gold quality
vagina	UBERON:0000996	94.85	gold quality
periodontal ligament	UBERON:0008266	94.22	gold quality
right lobe of liver	UBERON:0001114	94.09	gold quality
liver	UBERON:0002107	94.03	gold quality
parietal pleura	UBERON:0002400	93.41	gold quality
parotid gland	UBERON:0001831	92.62	gold quality
pleura	UBERON:0000977	92.60	gold quality
uterine cervix	UBERON:0000002	92.55	gold quality
smooth muscle tissue	UBERON:0001135	92.48	gold quality
hair follicle	UBERON:0002073	91.90	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-97	yes	1936.40
E-GEOD-130473	yes	1893.04
E-MTAB-6701	yes	1087.43
E-MTAB-7008	yes	330.90
E-MTAB-5061	yes	15.17
E-HCAD-13	yes	13.28
E-CURD-112	yes	6.07
E-GEOD-106540	no	2304.72
E-GEOD-150728	no	1488.20
E-ENAD-20	no	426.01
E-MTAB-9067	no	3.63
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting TMEM45A, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-519D-5P	99.41	69.30	2057

Literature-anchored findings (GeneRIF, showing 10)

• Data suggest that high levels of TMEM45A expression in tumors may be indicative of potential resistance to cancer therapy, making TMEM45A an interesting biomarker for resistance. (PMID:22954140)
• TMEM45A expression is correlated to epidermal keratinization (PMID:24689342)
• knockdown of TMEM45A also inhibited cell adhesion as well as cell invasion. More importantly, suppression of TMEM45A notably downregulated the expression of TGF-b1, TGF-b2, RhoA and ROCK2. (PMID:25872785)
• our study suggests that TMEM45A may work as an oncogene and a new effective therapeutic target for glioma treatment. (PMID:26722455)
• Knockdown of TMEM45A overcomes multidrug resistance and epithelial-mesenchymal transition in human colorectal cancer cells through inhibition of TGF-beta signalling pathway. (PMID:31788833)
• Characterization of the role of TMEM45A in cancer cell sensitivity to cisplatin. (PMID:31801939)
• Transmembrane protein 45A regulates the proliferation, migration, and invasion of glioma cells through nuclear factor kappa-B. (PMID:32568829)
• TMEM45A Affects Proliferation, Apoptosis, Epithelial-Mesenchymal Transition, Migration, Invasion and Cisplatin Resistance of HPV-Positive Cervical Cancer Cell Lines. (PMID:34143331)
• Association of Variants in TMEM45A With Keratoglobus. (PMID:34410316)
• Pan-cancer analysis of TMEM45A and exploration of its prognostic value and mechanism in gastric cancer. (PMID:39097870)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem45a	ENSDARG00000070743
mus_musculus	Tmem45a	ENSMUSG00000022754
mus_musculus	Tmem45a2	ENSMUSG00000046748
rattus_norvegicus	Tmem45a	ENSRNOG00000042975
rattus_norvegicus	Tmem45a2	ENSRNOG00000051418

Paralogs (2): TMEM45B (ENSG00000151715), TEDDM1 (ENSG00000203730)

Protein

Protein identifiers

Transmembrane protein 45A — Q9NWC5 (reviewed: Q9NWC5)

Alternative names: DNA polymerase-transactivated protein 4, Dermal papilla-derived protein 7

All UniProt accessions (3): C9J9Z5, Q9NWC5, J3KQ06

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the TMEM45 family.

RefSeq proteins (2): NP_001350805, NP_060474* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006904	DUF716	Family
IPR042127	TMEM45	Family

Pfam: PF04819

UniProt features (14 total): helix 7, transmembrane region 5, chain 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7OQZ	ELECTRON MICROSCOPY	3.27

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWC5-F1	92.06	0.79

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, JAEGER_METASTASIS_DN, GTTAAAG_MIR302B, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, MARTINEZ_RB1_TARGETS_UP, GERY_CEBP_TARGETS, ROZANOV_MMP14_TARGETS_UP, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX5_DN, TSENG_IRS1_TARGETS_DN

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

608 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM45A	MINDY3	Q9H8M7	868
TMEM45A	GHITM	Q9H3K2	787
TMEM45A	COPS7A	Q9UBW8	714
TMEM45A	TMEM9	Q9P0T7	711
TMEM45A	TMEM14A	Q9Y6G1	599
TMEM45A	TMEM158	Q8WZ71	578
TMEM45A	TMEM88	Q6PEY1	541
TMEM45A	ARL6IP5	O75915	540
TMEM45A	ANO1	Q5XXA6	489
TMEM45A	TMEM25	Q86YD3	483
TMEM45A	PDCL	Q13371	480
TMEM45A	CD209	Q9NNX6	458
TMEM45A	NDC1	Q9BTX1	447
TMEM45A	TMEM213	A2RRL7	447
TMEM45A	PEDS1	A5PLL7	446

IntAct

36 interactions, top by confidence:

A	B	Type	Score
TMEM19	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
ERMP1	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
SSMEM1	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
ARLN	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
GJA8	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
APOA2	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
PLN	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
	TMEM45A	psi-mi:“MI:0915”(physical association)	0.560
TMEM45A	KCTD5	psi-mi:“MI:0915”(physical association)	0.400
M	TMEM45A	psi-mi:“MI:0915”(physical association)	0.370
Kctd5		psi-mi:“MI:0914”(association)	0.350
TMEM45A	MYH1	psi-mi:“MI:0914”(association)	0.350
TMEM45A	SSMEM1	psi-mi:“MI:0915”(physical association)	0.000
ARLN	TMEM45A	psi-mi:“MI:0915”(physical association)	0.000
TMEM45A	GJA8	psi-mi:“MI:0915”(physical association)	0.000
APOA2	TMEM45A	psi-mi:“MI:0915”(physical association)	0.000
PLN	TMEM45A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): TMEM45A (Affinity Capture-MS), TMEM45A (Two-hybrid), TMEM45A (Two-hybrid), TMEM45A (Two-hybrid), TMEM45A (Two-hybrid), TMEM45A (Two-hybrid), TMEM45A (Two-hybrid), TMEM45A (Two-hybrid), TUSC5 (Two-hybrid), PLN (Two-hybrid), MYH1 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), WNT5A (Affinity Capture-MS), KCTD17 (Affinity Capture-MS), ICK (Affinity Capture-MS)

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, Q810U2, Q8CHM9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1356 predictions. Top by Δscore:

Variant	Effect	Δscore
3:100558403:A:AG	acceptor_gain	1.0000
3:100558404:G:GG	acceptor_gain	1.0000
3:100558551:TC:T	donor_gain	1.0000
3:100558586:TCAGG:T	donor_loss	1.0000
3:100558588:AGGTG:A	donor_loss	1.0000
3:100558589:GGT:G	donor_loss	1.0000
3:100558590:GT:G	donor_loss	1.0000
3:100558591:T:A	donor_loss	1.0000
3:100568813:A:AG	acceptor_gain	1.0000
3:100568814:A:G	acceptor_gain	1.0000
3:100568817:TACAG:T	acceptor_loss	1.0000
3:100568819:CAGA:C	acceptor_loss	1.0000
3:100568820:A:AG	acceptor_gain	1.0000
3:100568820:AGA:A	acceptor_loss	1.0000
3:100568821:G:A	acceptor_loss	1.0000
3:100568821:G:GG	acceptor_gain	1.0000
3:100568821:GATT:G	acceptor_gain	1.0000
3:100576920:CTCA:C	acceptor_loss	1.0000
3:100576923:A:AG	acceptor_gain	1.0000
3:100576923:AG:A	acceptor_gain	1.0000
3:100576923:AGGTT:A	acceptor_gain	1.0000
3:100576924:G:GC	acceptor_loss	1.0000
3:100576924:G:GG	acceptor_gain	1.0000
3:100576924:GG:G	acceptor_gain	1.0000
3:100576924:GGT:G	acceptor_gain	1.0000
3:100576924:GGTT:G	acceptor_gain	1.0000
3:100576924:GGTTG:G	acceptor_gain	1.0000
3:100556862:T:G	donor_gain	0.9900
3:100558399:CATCA:C	acceptor_loss	0.9900
3:100558400:A:AG	acceptor_gain	0.9900

AlphaMissense

1798 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:100558578:T:A	W193R	0.983
3:100558578:T:C	W193R	0.983
3:100558554:A:C	S185R	0.979
3:100558556:T:A	S185R	0.979
3:100558556:T:G	S185R	0.979
3:100568863:G:C	W210C	0.979
3:100568863:G:T	W210C	0.979
3:100568912:T:A	W227R	0.977
3:100568912:T:C	W227R	0.977
3:100555263:G:C	G18R	0.976
3:100556846:T:A	W93R	0.971
3:100556846:T:C	W93R	0.971
3:100556886:G:A	G106D	0.971
3:100568861:T:A	W210R	0.970
3:100568861:T:C	W210R	0.970
3:100558572:G:A	G191R	0.969
3:100558572:G:C	G191R	0.969
3:100555264:G:A	G18D	0.964
3:100558575:A:C	S192R	0.963
3:100558577:C:A	S192R	0.963
3:100558577:C:G	S192R	0.963
3:100555243:G:A	G11E	0.962
3:100558573:G:A	G191E	0.961
3:100558491:G:C	G164R	0.959
3:100555242:G:A	G11R	0.957
3:100555242:G:C	G11R	0.957
3:100556885:G:C	G106R	0.957
3:100555232:T:A	H7Q	0.955
3:100555232:T:G	H7Q	0.955
3:100558572:G:T	G191W	0.955

dbSNP variants (sampled 300 via entrez): RS1000011637 (3:100576008 T>C), RS1000032369 (3:100544810 G>A), RS1000097879 (3:100542458 A>G,T), RS1000102076 (3:100575798 A>G), RS1000118276 (3:100538201 G>A), RS1000209714 (3:100564473 TG>T), RS1000242353 (3:100523198 A>G), RS1000290713 (3:100567714 C>A), RS1000291692 (3:100505639 G>A), RS1000293564 (3:100577830 C>T), RS1000316382 (3:100522837 C>T), RS1000320675 (3:100505454 A>C), RS1000332069 (3:100524900 GA>G), RS1000383149 (3:100525141 CTG>C), RS1000422366 (3:100561216 G>A)

Disease associations

OMIM: gene MIM:616928 | 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
GCST004574_5	Skin aging (microtopography measurement)	1.000000e-06
GCST010002_434	Refractive error	5.000000e-25

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oxygen	decreases reaction, increases expression	6
methylmercuric chloride	decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Arsenic	increases abundance, increases ubiquitination, decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	increases expression	2
Particulate Matter	increases abundance, decreases expression	2
aristolochic acid I	decreases expression	1
1-cyclopropyl-4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl)pyridin-2-yl)piperazine	decreases reaction, increases expression	1
sotorasib	affects cotreatment, decreases expression	1
tungsten carbide	increases expression, affects cotreatment	1
bisphenol A	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
zinc chloride	decreases reaction, increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression, decreases reaction	1
nickel chloride	increases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1

Clinical trials (associated diseases)

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