TMEM205

Summary

TMEM205 (transmembrane protein 205, HGNC:29631) is a protein-coding gene on chromosome 19p13.2, encoding Transmembrane protein 205 (Q6UW68). In cancer cells, plays a role in resistance to the chemotherapeutic agent cisplatin.

Predicted to be located in membrane.

Source: NCBI Gene 374882 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 41 total
• Druggable target: yes
• MANE Select transcript: NM_198536

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29631
Approved symbol	TMEM205
Name	transmembrane protein 205
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	UNQ501, MBC3205
Ensembl gene	ENSG00000105518
Ensembl biotype	protein_coding
OMIM	613771
Entrez	374882

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 retained_intron

ENST00000354882, ENST00000447337, ENST00000585722, ENST00000586218, ENST00000586590, ENST00000586701, ENST00000586956, ENST00000587948, ENST00000588321, ENST00000588560, ENST00000589555, ENST00000590482, ENST00000590788, ENST00000591677, ENST00000592952, ENST00000593256, ENST00000853514

RefSeq mRNA: 6 — MANE Select: NM_198536 NM_001145416, NM_001321112, NM_001321113, NM_001321114, NM_033408, NM_198536

CCDS: CCDS32909

Canonical transcript exons

ENST00000354882 — 3 exons

Exon	Start	End
ENSE00002823954	11345520	11346268
ENSE00003509593	11342778	11343120
ENSE00003785725	11345252	11345415

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2676 / max 125.1835, expressed in 1794 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179217	17.2676	1794
179216	4.3275	1565
179215	3.1797	1149
179213	1.4012	598
179214	0.5863	281
179219	0.0870	22
179220	0.0415	16
179218	0.0089	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left adrenal gland cortex	UBERON:0035825	98.60	gold quality
right adrenal gland	UBERON:0001233	98.56	gold quality
left adrenal gland	UBERON:0001234	98.53	gold quality
right adrenal gland cortex	UBERON:0035827	98.49	gold quality
right lobe of liver	UBERON:0001114	98.45	gold quality
right lobe of thyroid gland	UBERON:0001119	98.44	gold quality
kidney epithelium	UBERON:0004819	98.43	gold quality
left lobe of thyroid gland	UBERON:0001120	98.31	gold quality
adrenal cortex	UBERON:0001235	98.18	gold quality
metanephros cortex	UBERON:0010533	98.15	gold quality
thyroid gland	UBERON:0002046	97.82	gold quality
apex of heart	UBERON:0002098	97.66	gold quality
adenohypophysis	UBERON:0002196	97.59	gold quality
right frontal lobe	UBERON:0002810	97.56	gold quality
prefrontal cortex	UBERON:0000451	97.55	gold quality
adrenal gland	UBERON:0002369	97.54	gold quality
body of pancreas	UBERON:0001150	97.53	gold quality
right uterine tube	UBERON:0001302	97.50	gold quality
liver	UBERON:0002107	97.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.43	gold quality
anterior cingulate cortex	UBERON:0009835	97.42	gold quality
caudate nucleus	UBERON:0001873	97.41	gold quality
putamen	UBERON:0001874	97.31	gold quality
right atrium auricular region	UBERON:0006631	97.28	gold quality
adult mammalian kidney	UBERON:0000082	97.27	gold quality
nucleus accumbens	UBERON:0001882	97.27	gold quality
pituitary gland	UBERON:0000007	97.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.11	gold quality
hypothalamus	UBERON:0001898	97.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-88	yes	81.23
E-HCAD-5	yes	34.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Results indicate that a novel mechanism for cisplatin resistance is mediated by TMEM205 overexpression. (PMID:20589834)
• The genetic polymorphisms in OCT2, AQP2, AQP9 and TMEM205 may contribute to chemotherapy response in lung cancer patients. (PMID:24643204)
• A recombinant platform to characterize the role of transmembrane protein hTMEM205 in Pt(II)-drug resistance and extrusion. (PMID:32789331)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem205	ENSDARG00000100677
mus_musculus	Tmem205	ENSMUSG00000040883
rattus_norvegicus	Tmem205	ENSRNOG00000011747
caenorhabditis_elegans		WBGENE00002263

Protein

Protein identifiers

Transmembrane protein 205 — Q6UW68 (reviewed: Q6UW68)

All UniProt accessions (7): Q6UW68, K7EJQ9, K7ELQ9, K7EM09, K7EMV9, K7EPR0, K7ER05

UniProt curated annotations — full annotation on UniProt →

Function. In cancer cells, plays a role in resistance to the chemotherapeutic agent cisplatin.

Subcellular location. Membrane.

Tissue specificity. Widely expressed with highest levels in pancreas, followed by adrenal gland, thyroid, liver, mammary gland, prostate, kidney, and retina; lowest levels in skeletal muscle. Overexpressed in cisplatin-resistant cancer cells (at protein level).

Similarity. Belongs to the TMEM205 family.

RefSeq proteins (6): NP_001138888, NP_001308041, NP_001308042, NP_001308043, NP_212133, NP_940938* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025423	TMEM205-like	Domain
IPR042623	TMEM205	Family

Pfam: PF13664

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UW68-F1	93.19	0.81

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 81 (showing top): YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, LEIN_PONS_MARKERS, chr19p13, ASH1L_TARGET_GENES, CEBPZ_TARGET_GENES, DIDO1_TARGET_GENES, HES2_TARGET_GENES, HMG20B_TARGET_GENES, LHX9_TARGET_GENES, NKX2_2_TARGET_GENES, PAX3_TARGET_GENES, PAX7_TARGET_GENES, TEAD2_TARGET_GENES, ZBTB12_TARGET_GENES, ZFHX3_TARGET_GENES

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

622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM205	TMEM14A	Q9Y6G1	637
TMEM205	GRAMD1C	Q8IYS0	464
TMEM205	CCDC159	P0C7I6	451
TMEM205	RAB8A	P24407	447
TMEM205	OCEL1	Q9H607	446
TMEM205	WDR17	Q8IZU2	441
TMEM205	TTC9	Q92623	440
TMEM205	ABCB11	O95342	415
TMEM205	EFR3B	Q9Y2G0	412
TMEM205	MSLNL	Q96KJ4	410
TMEM205	TM9SF3	Q9HD45	402
TMEM205	FKBP10	Q96AY3	399
TMEM205	TMEM213	A2RRL7	398
TMEM205	TMEM88	Q6PEY1	396
TMEM205	NDC1	Q9BTX1	392

IntAct

99 interactions, top by confidence:

A	B	Type	Score
COMT	TMEM205	psi-mi:“MI:0915”(physical association)	0.670
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
PLN	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
TMEM205	TREX1	psi-mi:“MI:0915”(physical association)	0.560
STX6	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
VAMP4	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
STX7	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
GOSR2	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
TMEM205	TMEM140	psi-mi:“MI:0915”(physical association)	0.560
TMEM205	STX8	psi-mi:“MI:0915”(physical association)	0.560
TMEM11	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
SMAGP	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
TMEM205	VRK2	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
TMEM205	ARL6IP6	psi-mi:“MI:0915”(physical association)	0.560
BNIP3	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
HTT	TMEM205	psi-mi:“MI:0915”(physical association)	0.560
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
HMOX2	PRAF2	psi-mi:“MI:0914”(association)	0.530
TMEM205	RBP4	psi-mi:“MI:0914”(association)	0.530

BioGRID (107): TMEM205 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), RBP4 (Affinity Capture-MS), TPM2 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), CORO1A (Affinity Capture-MS)

ESM2 similar proteins: A0A067XMT5, A0A2I1C3V3, A0A4P8DK01, A1L2F6, A4DA06, A7S6Y0, A9UY97, M3APK4, O64761, O97681, P15920, P25338, P58021, P70245, Q06089, Q0WQG8, Q12116, Q18319, Q28GF5, Q28GF8, Q32L10, Q3TUD9, Q4V7N7, Q5F410, Q5R8Y6, Q5REM8, Q60490, Q63175, Q641M3, Q66HF2, Q66HG5, Q6DGF8, Q6GPW4, Q6PD82, Q6UW68, Q7T163, Q8RWW1, Q91XE8, Q920R6, Q940G0

Diamond homologs: A1L2F6, Q28GF8, Q32L10, Q5REM8, Q6GPW4, Q6UW68, Q91XE8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

880 predictions. Top by Δscore:

Variant	Effect	Δscore
19:11343120:GCT:G	acceptor_loss	1.0000
19:11343121:C:CC	acceptor_gain	1.0000
19:11345248:GTAC:G	donor_loss	1.0000
19:11345249:TAC:T	donor_loss	1.0000
19:11343116:TAAAG:T	acceptor_gain	0.9900
19:11343117:AAAG:A	acceptor_gain	0.9900
19:11343118:AAG:A	acceptor_gain	0.9900
19:11343119:AG:A	acceptor_gain	0.9900
19:11343122:T:C	acceptor_loss	0.9900
19:11343125:C:CT	acceptor_gain	0.9900
19:11343126:A:T	acceptor_gain	0.9900
19:11345251:CCTGG:C	donor_gain	0.9900
19:11345414:GC:G	acceptor_gain	0.9900
19:11345414:GCCTG:G	acceptor_loss	0.9900
19:11345415:CC:C	acceptor_gain	0.9900
19:11345415:CCT:C	acceptor_loss	0.9900
19:11345416:C:CC	acceptor_gain	0.9900
19:11345417:T:A	acceptor_loss	0.9900
19:11345419:CAGGG:C	acceptor_gain	0.9900
19:11345423:G:C	acceptor_gain	0.9900
19:11345425:A:C	acceptor_gain	0.9900
19:11345515:CCTAC:C	donor_loss	0.9900
19:11345517:TA:T	donor_loss	0.9900
19:11346056:AT:A	donor_gain	0.9900
19:11346057:T:TA	donor_gain	0.9900
19:11345342:G:GT	donor_gain	0.9800
19:11345381:GGTA:G	donor_loss	0.9800
19:11345382:G:GC	donor_loss	0.9800
19:11345423:G:GC	acceptor_gain	0.9800
19:11345425:A:AC	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000270331 (19:11344732 G>C), RS1001271723 (19:11346682 G>A,T), RS1002544834 (19:11343856 C>T), RS1002597718 (19:11343599 A>G), RS1002668936 (19:11345023 T>A,C,G), RS1003102683 (19:11342352 T>C), RS1003334766 (19:11348208 G>A), RS1004515831 (19:11343937 C>T), RS1005653832 (19:11347526 C>A,T), RS1005939998 (19:11346410 T>C), RS1006451546 (19:11345705 G>A), RS1007118339 (19:11347147 C>G), RS1007461649 (19:11347408 G>A), RS1007507707 (19:11347600 G>A), RS1008004682 (19:11343801 A>C)

Disease associations

OMIM: gene MIM:613771 | 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: yes

ChEMBL targets (1): CHEMBL6067185 (SINGLE PROTEIN)

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs172731	RAB3D, TMEM205		0.00	0
rs896412	RAB3D, TMEM205		0.00	0
rs7251786	CCDC159, PLPPR2, TMEM205		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.08	Kd	8223	nM	CHEMBL5653589
5.08	ED50	8223	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149612: Binding affinity to human TMEM205 incubated for 45 mins by Kinobead based pull down assay	kd	8.2230	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
Cisplatin	increases expression, decreases response to substance, increases reaction, decreases uptake	3
bisphenol A	increases reaction, increases expression, affects binding	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	affects expression	1
beta-lapachone	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
entinostat	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Cadmium	increases abundance, increases expression	1
Estradiol	increases reaction, affects binding	1
Gallic Acid	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652654	Binding	Binding affinity to human TMEM205 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TS89	HAP1 TMEM205 (-) 1	Cancer cell line	Male
CVCL_XU46	HAP1 TMEM205 (-) 2	Cancer cell line	Male
CVCL_XU47	HAP1 TMEM205 (-) 3	Cancer cell line	Male
CVCL_XU48	HAP1 TMEM205 (-) 4	Cancer cell line	Male
CVCL_XU49	HAP1 TMEM205 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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