TMEM209

Summary

TMEM209 (transmembrane protein 209, HGNC:21898) is a protein-coding gene on chromosome 7q32.2, encoding Transmembrane protein 209 (Q96SK2). Nuclear envelope protein which in association with NUP205, may be involved in nuclear transport of various nuclear proteins in addition to MYC.

Predicted to be located in Golgi apparatus and nuclear envelope. Predicted to be active in membrane.

Source: NCBI Gene 84928 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_032842

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21898
Approved symbol	TMEM209
Name	transmembrane protein 209
Location	7q32.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14803, NET31
Ensembl gene	ENSG00000146842
Ensembl biotype	protein_coding
Entrez	84928

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 retained_intron

ENST00000397622, ENST00000462753, ENST00000467599, ENST00000471077, ENST00000471985, ENST00000473456, ENST00000479804, ENST00000869343, ENST00000869344, ENST00000869345, ENST00000936282, ENST00000936283, ENST00000951223

RefSeq mRNA: 3 — MANE Select: NM_032842 NM_001301163, NM_001363478, NM_032842

CCDS: CCDS47712, CCDS75661, CCDS87547

Canonical transcript exons

ENST00000397622 — 15 exons

Exon	Start	End
ENSE00000977721	130203788	130203846
ENSE00000977722	130202532	130202663
ENSE00000977726	130184184	130184255
ENSE00000977727	130181623	130181719
ENSE00000977728	130178402	130178527
ENSE00000977729	130175512	130175609
ENSE00000977730	130173825	130173939
ENSE00000977731	130173632	130173729
ENSE00000977732	130170400	130170473
ENSE00001206911	130185192	130185367
ENSE00001206917	130192622	130192823
ENSE00001399878	130201850	130202091
ENSE00001529430	130164713	130166505
ENSE00002231198	130205373	130205406
ENSE00003756718	130203974	130204110

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 91.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.9776 / max 341.5905, expressed in 1797 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86115	21.2219	1795
86116	0.7476	427
86117	0.0082	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	91.81	gold quality
germinal epithelium of ovary	UBERON:0001304	88.44	gold quality
pigmented layer of retina	UBERON:0001782	88.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.96	gold quality
left adrenal gland	UBERON:0001234	86.96	gold quality
right adrenal gland	UBERON:0001233	86.88	gold quality
right adrenal gland cortex	UBERON:0035827	86.86	gold quality
adrenal gland	UBERON:0002369	86.63	gold quality
palpebral conjunctiva	UBERON:0001812	86.21	gold quality
left adrenal gland cortex	UBERON:0035825	86.02	gold quality
secondary oocyte	CL:0000655	85.71	gold quality
adrenal cortex	UBERON:0001235	85.15	gold quality
islet of Langerhans	UBERON:0000006	85.08	gold quality
tibia	UBERON:0000979	84.65	gold quality
epithelium of nasopharynx	UBERON:0001951	84.63	gold quality
colonic epithelium	UBERON:0000397	84.50	gold quality
visceral pleura	UBERON:0002401	84.41	gold quality
jejunal mucosa	UBERON:0000399	84.28	gold quality
parietal pleura	UBERON:0002400	84.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.23	gold quality
calcaneal tendon	UBERON:0003701	84.12	gold quality
corpus epididymis	UBERON:0004359	83.71	gold quality
pleura	UBERON:0000977	83.50	gold quality
rectum	UBERON:0001052	82.94	gold quality
oocyte	CL:0000023	82.48	gold quality
endometrium	UBERON:0001295	82.37	gold quality
stromal cell of endometrium	CL:0002255	82.08	gold quality
tonsil	UBERON:0002372	81.60	gold quality
ventricular zone	UBERON:0003053	81.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

95 targeting TMEM209, 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-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
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-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4659A-3P	99.80	72.62	4248

Literature-anchored findings (GeneRIF, showing 1)

• Findings indicate that TMEM209 overexpression and TMEM209-NUP205 interaction are critical drivers of lung cancer proliferation. (PMID:22719065)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem209	ENSDARG00000039340
mus_musculus	Tmem209	ENSMUSG00000029782
rattus_norvegicus	Tmem209	ENSRNOG00000028219
drosophila_melanogaster	CG6479	FBGN0036710
caenorhabditis_elegans		WBGENE00007186

Protein

Protein identifiers

Transmembrane protein 209 — Q96SK2 (reviewed: Q96SK2)

All UniProt accessions (4): Q96SK2, A0A140VJX5, C9J5K4, C9JYX1

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear envelope protein which in association with NUP205, may be involved in nuclear transport of various nuclear proteins in addition to MYC.

Subunit / interactions. Interacts with NUP205.

Subcellular location. Membrane. Nucleus envelope. Golgi apparatus. Cytoplasm.

Tissue specificity. Expressed in the testis.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96SK2-1	1	yes
Q96SK2-2	2
Q96SK2-3	3
Q96SK2-4	4

RefSeq proteins (3): NP_001288092, NP_001350407, NP_116231* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019176	Cytochrome_B561-rel	Family

Pfam: PF09786

UniProt features (26 total): modified residue 7, splice variant 4, region of interest 3, compositionally biased region 3, transmembrane region 2, glycosylation site 2, sequence variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96SK2-F1	69.68	0.30

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 (7): 11, 98, 201, 222, 248, 278, 9

Glycosylation sites (2): 57, 274

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 144 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, HNF3ALPHA_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, EFC_Q6, chr7q32, HFH3_01, DODD_NASOPHARYNGEAL_CARCINOMA_UP, RYTTCCTG_ETS2_B, FISCHER_DREAM_TARGETS, ZHANG_BREAST_CANCER_PROGENITORS_UP, ACEVEDO_LIVER_CANCER_UP, FOX_Q2, GOCC_NUCLEAR_ENVELOPE, NUYTTEN_EZH2_TARGETS_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (5): nuclear envelope (GO:0005635), Golgi apparatus (GO:0005794), membrane (GO:0016020), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
nucleus	1
organelle envelope	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

800 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM209	NUP205	Q92621	721
TMEM209	TMEM126A	Q9H061	528
TMEM209	TMEM53	Q6P2H8	505
TMEM209	TSGA13	Q96PP4	475
TMEM209	NCLN	Q969V3	474
TMEM209	PLPP7	Q8NBV4	453
TMEM209	LYRM7	Q5U5X0	450
TMEM209	CGGBP1	Q9UFW8	450
TMEM209	PUM3	Q15397	443
TMEM209	DDO	Q99489	442
TMEM209	CYBC1	Q9BQA9	433
TMEM209	ABHD10	Q9NUJ1	424
TMEM209	MIX23	Q4VC31	424
TMEM209	SCCPDH	Q8NBX0	419
TMEM209	ERMP1	Q7Z2K6	411

IntAct

80 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
TMEM209	APOL2	psi-mi:“MI:0915”(physical association)	0.400
TMEM209	NAB2	psi-mi:“MI:0915”(physical association)	0.400
Tuba3a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Nup98	POM121C	psi-mi:“MI:0914”(association)	0.350
Nup107	POM121C	psi-mi:“MI:0914”(association)	0.350
Nup155	AP3B1	psi-mi:“MI:0914”(association)	0.350
Ranbp2	POM121C	psi-mi:“MI:0914”(association)	0.350
Rcc1	WDR46	psi-mi:“MI:0914”(association)	0.350
Ube2i	POM121C	psi-mi:“MI:0914”(association)	0.350
Smn1	CLNS1A	psi-mi:“MI:0914”(association)	0.350
NUP153	POM121C	psi-mi:“MI:0914”(association)	0.350
SEH1L	POM121C	psi-mi:“MI:0914”(association)	0.350
UBE2I	NUP155	psi-mi:“MI:0914”(association)	0.350
TUBA1C	TCP11L2	psi-mi:“MI:0914”(association)	0.350
NUP107	POM121C	psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350

BioGRID (210): TMEM209 (Synthetic Growth Defect), TMEM209 (Affinity Capture-MS), TMEM209 (Proximity Label-MS), TMEM209 (Proximity Label-MS), TMEM209 (Proximity Label-MS), TMEM209 (Proximity Label-MS), TMEM209 (Proximity Label-MS), TMEM209 (Affinity Capture-MS), TMEM209 (Affinity Capture-MS), TMEM209 (Affinity Capture-MS), TMEM209 (Affinity Capture-MS), TMEM209 (Affinity Capture-MS), TMEM209 (Affinity Capture-MS), TMEM209 (Affinity Capture-MS), TMEM209 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUI7, A1DL98, A1L1K4, A4V8B4, A6QLJ4, A6ZMG4, A6ZR60, A7NVJ4, A9JR56, B3LLZ8, C5E1C7, C7GWA2, C8ZEW0, O13916, O60153, P0C2W9, P15130, P16135, P20486, P27271, P28974, P35198, P40063, P84395, Q04438, Q28EW5, Q28GG3, Q4V853, Q5FVD7, Q5R4F8, Q5R977, Q5RD94, Q5U550, Q66657, Q68EK9, Q68FR5, Q6AX78, Q6C3T0, Q751I6, Q7T2A3

Diamond homologs: Q03564, Q5M7R3, Q68FR5, Q6GPP7, Q8BRG8, Q96SK2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of Ribonucleoproteins into the Host Nucleus	6	31.5×	8e-06
Postmitotic nuclear pore complex (NPC) reformation	5	30.0×	3e-05
Nuclear import of Rev protein	6	29.6×	8e-06
SUMOylation of SUMOylation proteins	6	28.8×	8e-06
IPs transport between nucleus and cytosol	5	28.0×	3e-05
IP3 and IP4 transport between cytosol and nucleus	5	28.0×	3e-05
IP6 and IP7 transport between cytosol and nucleus	5	28.0×	3e-05
Regulation of Glucokinase by Glucokinase Regulatory Protein	5	26.2×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2264 predictions. Top by Δscore:

Variant	Effect	Δscore
7:130170470:TGCCC:T	acceptor_loss	1.0000
7:130170472:CCCTG:C	acceptor_loss	1.0000
7:130170473:CCTGG:C	acceptor_loss	1.0000
7:130170474:C:CC	acceptor_gain	1.0000
7:130170474:CT:C	acceptor_loss	1.0000
7:130170475:T:A	acceptor_loss	1.0000
7:130173819:TTATA:T	donor_loss	1.0000
7:130173820:TATA:T	donor_loss	1.0000
7:130173821:ATACC:A	donor_loss	1.0000
7:130173822:TACC:T	donor_loss	1.0000
7:130173823:A:C	donor_loss	1.0000
7:130173824:C:CA	donor_loss	1.0000
7:130184182:A:AC	donor_gain	1.0000
7:130184183:C:CC	donor_gain	1.0000
7:130184183:CATT:C	donor_gain	1.0000
7:130184183:CATTT:C	donor_gain	1.0000
7:130185187:CTTA:C	donor_loss	1.0000
7:130185188:TTA:T	donor_loss	1.0000
7:130185189:TA:T	donor_loss	1.0000
7:130185190:A:AC	donor_gain	1.0000
7:130185191:C:CC	donor_gain	1.0000
7:130185191:C:CG	donor_loss	1.0000
7:130185191:CCT:C	donor_gain	1.0000
7:130185364:CTCC:C	acceptor_gain	1.0000
7:130185365:TCC:T	acceptor_gain	1.0000
7:130185366:CC:C	acceptor_gain	1.0000
7:130185366:CCC:C	acceptor_gain	1.0000
7:130185367:CC:C	acceptor_gain	1.0000
7:130185368:C:CA	acceptor_loss	1.0000
7:130185368:C:CC	acceptor_gain	1.0000

AlphaMissense

3684 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:130166482:C:T	G552D	0.999
7:130166483:C:G	G552R	0.999
7:130181719:A:G	W342R	0.999
7:130181719:A:T	W342R	0.999
7:130166483:C:A	G552C	0.998
7:130166494:A:G	L548P	0.998
7:130173666:A:G	L508P	0.998
7:130173863:A:G	F474S	0.998
7:130173909:C:G	D459H	0.998
7:130173911:A:G	L458P	0.998
7:130175520:C:G	D446H	0.998
7:130175606:A:G	L417P	0.998
7:130181703:A:T	I347K	0.998
7:130184187:T:A	R340S	0.998
7:130184187:T:G	R340S	0.998
7:130184188:C:G	R340T	0.998
7:130166475:A:C	N554K	0.997
7:130166475:A:T	N554K	0.997
7:130166482:C:A	G552V	0.997
7:130166494:A:C	L548R	0.997
7:130166494:A:T	L548H	0.997
7:130170403:A:G	L543P	0.997
7:130175541:A:G	W439R	0.997
7:130175541:A:T	W439R	0.997
7:130175574:A:G	W428R	0.997
7:130175574:A:T	W428R	0.997
7:130178446:A:G	L401P	0.997
7:130166492:C:G	G549R	0.996
7:130166496:A:C	N547K	0.996
7:130166496:A:T	N547K	0.996

dbSNP variants (sampled 300 via entrez): RS1000055450 (7:130196502 G>A), RS1000063546 (7:130189712 A>G), RS1000072824 (7:130173230 T>C), RS1000146722 (7:130192021 T>C), RS1000199900 (7:130199284 C>G), RS1000248991 (7:130185771 C>T), RS1000301121 (7:130186154 TTAAC>T), RS1000331890 (7:130179927 C>G), RS1000404867 (7:130192640 G>A), RS1000417330 (7:130186085 G>A), RS1000502851 (7:130198085 C>T), RS1000672080 (7:130192405 C>G,T), RS1000689896 (7:130174850 G>C), RS1000733693 (7:130192958 T>A), RS1000751946 (7:130184383 A>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

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression, increases expression	4
trichostatin A	affects cotreatment, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Ozone	decreases expression, increases abundance, affects expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Coal	decreases expression, increases abundance	1
Estradiol	affects expression	1
Hydrogen Peroxide	increases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression, increases abundance	1
Testosterone	increases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TS90	HAP1 TMEM209 (-) 1	Cancer cell line	Male
CVCL_TS91	HAP1 TMEM209 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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