TMEM208

Summary

TMEM208 (transmembrane protein 208, HGNC:25015) is a protein-coding gene on chromosome 16q22.1, encoding Transmembrane protein 208 (Q9BTX3). May function as a negative regulator of endoplasmic reticulum-stress induced autophagy.

This gene encodes a highly conserved protein which is localized in the endoplasmic reticulum (ER). The protein is linked to autophagy and ER stress. Knockdown of this gene increased autophagy and triggered ER stress. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 29100 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_014187

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25015
Approved symbol	TMEM208
Name	transmembrane protein 208
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	HSPC171, hSND2, SND2
Ensembl gene	ENSG00000168701
Ensembl biotype	protein_coding
OMIM	620781
Entrez	29100

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 retained_intron, 3 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000304800, ENST00000561586, ENST00000562235, ENST00000563168, ENST00000563271, ENST00000563426, ENST00000563953, ENST00000564087, ENST00000564649, ENST00000565201, ENST00000566486, ENST00000567193

RefSeq mRNA: 2 — MANE Select: NM_014187 NM_001318217, NM_014187

CCDS: CCDS45511, CCDS81996

Canonical transcript exons

ENST00000304800 — 6 exons

Exon	Start	End
ENSE00003501681	67227130	67227224
ENSE00003504156	67228976	67229278
ENSE00003579378	67228355	67228414
ENSE00003617716	67227836	67227931
ENSE00003621671	67228495	67228631
ENSE00003664069	67228797	67228881

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 96.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.3055 / max 172.4219, expressed in 1821 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154608	31.3055	1821

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	96.88	gold quality
right adrenal gland	UBERON:0001233	96.62	gold quality
left adrenal gland	UBERON:0001234	96.58	gold quality
left adrenal gland cortex	UBERON:0035825	96.58	gold quality
right lobe of liver	UBERON:0001114	96.51	gold quality
right adrenal gland cortex	UBERON:0035827	96.33	gold quality
adenohypophysis	UBERON:0002196	96.14	gold quality
mucosa of transverse colon	UBERON:0004991	96.07	gold quality
adrenal cortex	UBERON:0001235	95.90	gold quality
body of pancreas	UBERON:0001150	95.51	gold quality
pituitary gland	UBERON:0000007	95.34	gold quality
periodontal ligament	UBERON:0008266	95.28	gold quality
adrenal gland	UBERON:0002369	95.26	gold quality
pancreas	UBERON:0001264	95.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.66	gold quality
stromal cell of endometrium	CL:0002255	94.53	gold quality
metanephros cortex	UBERON:0010533	94.41	gold quality
body of stomach	UBERON:0001161	94.35	gold quality
right lobe of thyroid gland	UBERON:0001119	94.33	gold quality
left lobe of thyroid gland	UBERON:0001120	94.04	gold quality
minor salivary gland	UBERON:0001830	93.79	gold quality
prefrontal cortex	UBERON:0000451	93.59	gold quality
rectum	UBERON:0001052	93.55	gold quality
lower esophagus mucosa	UBERON:0035834	93.45	gold quality
anterior cingulate cortex	UBERON:0009835	93.36	gold quality
liver	UBERON:0002107	93.24	gold quality
cingulate cortex	UBERON:0003027	93.24	gold quality
thyroid gland	UBERON:0002046	93.16	gold quality
granulocyte	CL:0000094	92.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.98	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	85.77
E-MTAB-9467	yes	49.44
E-CURD-122	yes	37.49
E-HCAD-5	yes	34.27
E-CURD-46	yes	13.78
E-HCAD-1	yes	10.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting TMEM208, 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-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-588	96.45	68.36	1127
HSA-MIR-95-3P	89.95	66.87	81

Literature-anchored findings (GeneRIF, showing 6)

• novel ER-located protein regulates both ER stress and autophagy (PMID:23691174)
• Snd2 protein represents an alternative targeting factor to the endoplasmic reticulum in human cells. (PMID:28862756)
• hSnd2/TMEM208 is an HIF-1alpha-targeted gene and contains a WH2 motif. (PMID:32002553)
• Human SND2 mediates ER targeting of GPI-anchored proteins with low hydrophobic GPI attachment signals. (PMID:33838053)
• Loss of the endoplasmic reticulum protein Tmem208 affects cell polarity, development, and viability. (PMID:38381787)
• Exploring the Role and Prognostic Value of TMEM208 in Head and Neck Squamous Cell Carcinoma. (PMID:38546073)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem208	ENSDARG00000068291
mus_musculus	Tmem208	ENSMUSG00000014856
rattus_norvegicus	Tmem208	ENSRNOG00000015974
drosophila_melanogaster	CG8320	FBGN0034059
caenorhabditis_elegans	tmem-208	WBGENE00011033

Protein

Protein identifiers

Transmembrane protein 208 — Q9BTX3 (reviewed: Q9BTX3)

All UniProt accessions (4): Q9BTX3, H3BMW4, J3KRY7, J3QRY9

UniProt curated annotations — full annotation on UniProt →

Function. May function as a negative regulator of endoplasmic reticulum-stress induced autophagy.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the TMEM208 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BTX3-1	1	yes
Q9BTX3-2	2

RefSeq proteins (2): NP_001305146, NP_054906* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008506	SND2/TMEM208	Family

Pfam: PF05620

UniProt features (12 total): transmembrane region 3, sequence variant 3, chain 1, sequence conflict 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTX3-F1	78.49	0.24

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 (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, chr16q22, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, AP2_Q3, GOBP_PROTEIN_MATURATION, ELK1_01, NRF2_01, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOBP_PROTEOLYSIS, BLALOCK_ALZHEIMERS_DISEASE_DN, SCGGAAGY_ELK1_02, GOCC_ORGANELLE_SUBCOMPARTMENT, STAT5A_01, MGGAAGTG_GABP_B, ATGGYGGA_UNKNOWN

GO Biological Process (2): vacuolar protein processing (GO:0006624), autophagy (GO:0006914)

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

GO Cellular Component (4): vacuole (GO:0005773), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular membrane-bounded organelle	2
vacuole	1
protein processing	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

926 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM208	WDR83OS	Q9Y284	650
TMEM208	FBXL8	Q96CD0	616
TMEM208	GET3	O43681	580
TMEM208	GET1	O00258	572
TMEM208	SND1	Q7KZF4	515
TMEM208	TMEM101	Q96IK0	510
TMEM208	GET4	Q7L5D6	490
TMEM208	RBM42	Q9BTD8	488
TMEM208	SLC35B1	P78383	477
TMEM208	TMEM59L	Q9UK28	475
TMEM208	SEC61A1	P38378	471
TMEM208	ARFGEF1	Q9Y6D6	468
TMEM208	TMEM115	Q12893	468
TMEM208	WDFY4	Q6ZS81	453
TMEM208	CAMLG	P49069	449

IntAct

73 interactions, top by confidence:

A	B	Type	Score
TMEM208	C10orf67	psi-mi:“MI:0915”(physical association)	0.560
TMEM208	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
TMEM208	SPG21	psi-mi:“MI:0915”(physical association)	0.560
	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
TMEM208	NDRG4	psi-mi:“MI:0915”(physical association)	0.560
SCARA5	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
KCNJ6	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
GPR152	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
REEP2	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
RNF19B	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
SLC30A8	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
EBP	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
STOM	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
TMEM208	GPRC5D	psi-mi:“MI:0915”(physical association)	0.560
TMEM208	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
C10orf67	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
TMEM208	REEP4	psi-mi:“MI:0915”(physical association)	0.560
TMEM208	TMX2	psi-mi:“MI:0915”(physical association)	0.560
MFSD14B	TMEM208	psi-mi:“MI:0915”(physical association)	0.560
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
TMEM208	CD63	psi-mi:“MI:0914”(association)	0.350
REEP5	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM208	SCAMP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): TMEM208 (Affinity Capture-MS), TMEM208 (Affinity Capture-MS), TMEM208 (Affinity Capture-MS), TMEM208 (Affinity Capture-MS), TMEM208 (Affinity Capture-MS), TMEM208 (Affinity Capture-MS), TMEM208 (Affinity Capture-MS), TMEM208 (Two-hybrid), TRPC6 (Affinity Capture-Western), TMEM208 (Affinity Capture-Western), TMEM208 (Co-localization), TRPC6 (Co-localization), TMEM208 (Positive Genetic), TMEM208 (Two-hybrid), TMEM208 (Two-hybrid)

ESM2 similar proteins: A1CIM7, A1CW41, A1ZA77, A2Q9P5, A3LRT4, A4RE85, A4RME3, A5DRE8, A5JYQ9, A6SFL7, A8N1Z1, B0Y4Q8, B2ALT5, B5XB24, O14193, O42940, O44953, O94673, P34669, P38166, P38264, Q0CSZ7, Q0IHJ0, Q0UV43, Q18449, Q1E9X9, Q2UUK2, Q3SZZ5, Q4V7N7, Q4WQJ5, Q54UB0, Q5ZK32, Q61CQ8, Q6BVH1, Q6GR43, Q6NYP0, Q6P011, Q6PBF7, Q7SGB6, Q86I95

Diamond homologs: A1ZA77, Q0IHJ0, Q3SZZ5, Q54UB0, Q5ZK32, Q6NYP0, Q9BTX3, Q9CR96

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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 small molecules	6	8.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

728 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67227831:TGCA:T	acceptor_loss	1.0000
16:67227832:GCA:G	acceptor_loss	1.0000
16:67227833:CAGC:C	acceptor_loss	1.0000
16:67227834:A:AG	acceptor_gain	1.0000
16:67227834:AGCC:A	acceptor_loss	1.0000
16:67227835:G:GA	acceptor_gain	1.0000
16:67227835:GC:G	acceptor_gain	1.0000
16:67227835:GCC:G	acceptor_gain	1.0000
16:67227835:GCCC:G	acceptor_gain	1.0000
16:67227835:GCCCA:G	acceptor_gain	1.0000
16:67227927:CCAAT:C	donor_gain	1.0000
16:67227928:CAAT:C	donor_gain	1.0000
16:67227928:CAATG:C	donor_loss	1.0000
16:67227929:AAT:A	donor_gain	1.0000
16:67227930:AT:A	donor_gain	1.0000
16:67227931:TGT:T	donor_loss	1.0000
16:67227932:G:GG	donor_gain	1.0000
16:67227932:GT:G	donor_loss	1.0000
16:67228413:GG:G	donor_gain	1.0000
16:67228414:GG:G	donor_gain	1.0000
16:67228415:G:GG	donor_gain	1.0000
16:67228492:CA:C	acceptor_loss	1.0000
16:67228493:A:AG	acceptor_gain	1.0000
16:67228493:AG:A	acceptor_loss	1.0000
16:67228493:AGTT:A	acceptor_gain	1.0000
16:67228493:AGTTG:A	acceptor_gain	1.0000
16:67228494:G:GC	acceptor_gain	1.0000
16:67228494:GT:G	acceptor_gain	1.0000
16:67228494:GTT:G	acceptor_gain	1.0000
16:67228494:GTTG:G	acceptor_gain	1.0000

AlphaMissense

1119 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67228607:T:A	L92H	0.999
16:67228806:G:C	K103N	0.999
16:67228806:G:T	K103N	0.999
16:67228510:A:C	S60R	0.998
16:67228512:T:A	S60R	0.998
16:67228512:T:G	S60R	0.998
16:67228607:T:C	L92P	0.998
16:67228843:A:C	S116R	0.998
16:67228845:C:A	S116R	0.998
16:67228845:C:G	S116R	0.998
16:67228873:T:A	W126R	0.998
16:67228873:T:C	W126R	0.998
16:67228989:C:A	A133D	0.998
16:67227885:A:T	N19I	0.997
16:67228531:A:C	S67R	0.997
16:67228533:C:A	S67R	0.997
16:67228533:C:G	S67R	0.997
16:67227861:G:A	G11E	0.996
16:67227886:C:A	N19K	0.996
16:67227886:C:G	N19K	0.996
16:67228802:T:C	L102P	0.996
16:67228807:G:C	D104H	0.996
16:67228808:A:C	D104A	0.996
16:67228809:T:A	D104E	0.996
16:67228809:T:G	D104E	0.996
16:67228864:T:A	W123R	0.996
16:67228864:T:C	W123R	0.996
16:67227860:G:A	G11R	0.995
16:67227860:G:C	G11R	0.995
16:67227884:A:C	N19H	0.995

dbSNP variants (sampled 300 via entrez): RS1001202273 (16:67227536 C>G), RS1002357307 (16:67228170 C>T), RS1002839456 (16:67227932 G>A,T), RS1003099010 (16:67226903 C>A,T), RS1003123024 (16:67227985 T>C), RS1003461732 (16:67226739 G>A,C), RS1003941777 (16:67226113 G>GATA), RS1005645736 (16:67226798 A>G,T), RS1006117998 (16:67229407 T>C), RS1007115283 (16:67227135 T>C), RS1007443951 (16:67225573 C>A), RS1008042699 (16:67228741 T>A), RS1009500793 (16:67226420 A>C), RS1009860154 (16:67226031 G>A), RS1010245135 (16:67226922 A>G)

Disease associations

OMIM: gene MIM:620781 | 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

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	2
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
quercitrin	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
zinc chromate	increases abundance, increases expression	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
abrine	increases expression	1
Decitabine	affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects expression	1
Copper	affects binding, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3JM	Abcam HEK293T TMEM208 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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