TMEM139

Summary

TMEM139 (transmembrane protein 139, HGNC:22058) is a protein-coding gene on chromosome 7q34, encoding Transmembrane protein 139 (Q8IV31). May be involved in cellular trafficking of proteins such as SLC4A1.

Predicted to be located in membrane.

Source: NCBI Gene 135932 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_001282876

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22058
Approved symbol	TMEM139
Name	transmembrane protein 139
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90586
Ensembl gene	ENSG00000178826
Ensembl biotype	protein_coding
OMIM	616524
Entrez	135932

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000359333, ENST00000409102, ENST00000409244, ENST00000409541, ENST00000410004, ENST00000471161, ENST00000480421, ENST00000482420, ENST00000487419, ENST00000882990, ENST00000882991, ENST00000882992, ENST00000927660, ENST00000946923

RefSeq mRNA: 6 — MANE Select: NM_001282876 NM_001242773, NM_001242774, NM_001242775, NM_001282876, NM_001282877, NM_153345

CCDS: CCDS5878

Canonical transcript exons

ENST00000359333 — 3 exons

Exon	Start	End
ENSE00001249174	143285941	143286202
ENSE00001952566	143284958	143285445
ENSE00003618605	143286424	143288048

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 95.73.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0956 / max 92.3124, expressed in 308 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81761	1.0956	308

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	95.73	gold quality
mucosa of transverse colon	UBERON:0004991	95.16	gold quality
jejunal mucosa	UBERON:0000399	94.56	gold quality
kidney epithelium	UBERON:0004819	94.43	gold quality
metanephros cortex	UBERON:0010533	93.61	gold quality
duodenum	UBERON:0002114	92.41	gold quality
adult mammalian kidney	UBERON:0000082	91.05	gold quality
kidney	UBERON:0002113	88.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.49	gold quality
cortex of kidney	UBERON:0001225	87.89	gold quality
right uterine tube	UBERON:0001302	87.42	gold quality
renal medulla	UBERON:0000362	87.03	gold quality
spinal cord	UBERON:0002240	86.12	gold quality
apex of heart	UBERON:0002098	85.59	gold quality
placenta	UBERON:0001987	85.39	gold quality
metanephros	UBERON:0000081	84.42	gold quality
left lobe of thyroid gland	UBERON:0001120	83.66	gold quality
right lobe of thyroid gland	UBERON:0001119	83.61	gold quality
pancreatic ductal cell	CL:0002079	83.48	silver quality
small intestine	UBERON:0002108	83.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.87	gold quality
thyroid gland	UBERON:0002046	82.64	gold quality
nasal cavity epithelium	UBERON:0005384	82.63	silver quality
right lobe of liver	UBERON:0001114	82.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.49	gold quality
gall bladder	UBERON:0002110	81.23	gold quality
right lung	UBERON:0002167	80.88	gold quality
body of pancreas	UBERON:0001150	80.82	gold quality
oviduct epithelium	UBERON:0004804	80.82	gold quality
transverse colon	UBERON:0001157	80.50	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.26
E-CURD-10	no	381.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting TMEM139, 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-570-3P	99.96	72.41	4910
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-744-3P	97.99	67.76	637
HSA-MIR-219B-5P	97.91	65.80	531
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-6501-5P	97.41	68.24	712
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-769-3P	97.06	64.83	464
HSA-MIR-6730-3P	97.03	67.54	889
HSA-MIR-6750-3P	96.79	67.50	740
HSA-MIR-3907	96.76	65.04	662

Literature-anchored findings (GeneRIF, showing 2)

• presented data demonstrate that TMEM139 interacts with kAE1 and promotes its intracellular trafficking (PMID:26049106)
• TMEM139 prevents NSCLC metastasis by inhibiting lysosomal degradation of E-cadherin. (PMID:35302694)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem139	ENSMUSG00000071506
rattus_norvegicus	Tmem139	ENSRNOG00000063089

Protein

Protein identifiers

Transmembrane protein 139 — Q8IV31 (reviewed: Q8IV31)

All UniProt accessions (1): Q8IV31

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in cellular trafficking of proteins such as SLC4A1.

Subunit / interactions. Interacts with isoform 2 of SLC4A1.

Subcellular location. Membrane.

RefSeq proteins (6): NP_001229702, NP_001229703, NP_001229704, NP_001269805, NP_001269806, NP_699176 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038805	TMEM139	Family

UniProt features (11 total): sequence conflict 2, topological domain 2, modified residue 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IV31-F1	64.82	0.13

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): 146, 155

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): AREB6_01, GGGTGGRR_PAX4_03, GOZGIT_ESR1_TARGETS_UP, MIKKELSEN_ES_ICP_WITH_H3K4ME3, CHEMNITZ_RESPONSE_TO_PROSTAGLANDIN_E2_DN, FORTSCHEGGER_PHF8_TARGETS_DN, LIM_MAMMARY_STEM_CELL_DN, FOXJ2_TARGET_GENES, SOX10_TARGET_GENES, ZFHX3_TARGET_GENES, ZNF22_TARGET_GENES, ZNF768_TARGET_GENES, MIR570_3P, MIR4306, MIR4644

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

200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM139	PROSER3	Q2NL68	528
TMEM139	THTPA	Q9BU02	506
TMEM139	CFAP119	A1A4V9	480
TMEM139	SLC4A1	P02730	478
TMEM139	PDCD7	Q8N8D1	379
TMEM139	TRAPPC9	Q96Q05	350
TMEM139	ZNF532	Q9HCE3	325
TMEM139	INAVA	Q3KP66	324
TMEM139	ZNF398	Q8TD17	312
TMEM139	OSGEP	Q9NPF4	305
TMEM139	FIGN	Q5HY92	298
TMEM139	PIPOX	Q9P0Z9	295
TMEM139	GJB5	O95377	293
TMEM139	PHKG2	P11800	290
TMEM139	PDE8B	O95263	273

IntAct

122 interactions, top by confidence:

A	B	Type	Score
KCNK1	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
NSG1	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
TMEM19	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
SFTPC	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
PLPP4	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0C	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
PPGB	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
CYB5B	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
TMEM107	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
TMEM139	UBIAD1	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
TMEM139	NINJ2	psi-mi:“MI:0915”(physical association)	0.560
PMP22	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
SEC22B	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
TMEM139	BCL2L2	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
MALL	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
NKG7	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
SLC35A1	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
TMEM139	SLC30A8	psi-mi:“MI:0915”(physical association)	0.560
TMEM139	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
TMEM139	NAPB	psi-mi:“MI:0915”(physical association)	0.560
TMEM139	CMTM5	psi-mi:“MI:0915”(physical association)	0.560
TMEM139	MARCHF5	psi-mi:“MI:0915”(physical association)	0.560
MIP	TMEM139	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (48): TRIM68 (Affinity Capture-MS), RPS6KA3 (Affinity Capture-MS), RPS6KA3 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), TMEM139 (Two-hybrid), TMEM139 (Two-hybrid), TMEM139 (Two-hybrid), TMEM139 (Two-hybrid), TMEM139 (Two-hybrid), TMEM139 (Two-hybrid), TMEM139 (Two-hybrid), TMEM139 (Two-hybrid), TMEM139 (Two-hybrid), TMEM139 (Two-hybrid), TMEM139 (Two-hybrid)

ESM2 similar proteins: A0A1B0GW64, A0PJX4, A2RRU4, A4D2P6, A6QM06, D4A6L0, E1BBQ2, F1LQY6, G3V9M2, O60320, O95644, P29590, P49796, P49797, P55199, P81408, P97260, Q12770, Q13387, Q15884, Q3UPR0, Q4FZH1, Q5HZJ5, Q5MNU5, Q5T848, Q69Z89, Q6A044, Q6GQT6, Q70EL4, Q8BGE4, Q8BHW5, Q8BUM9, Q8BX43, Q8C419, Q8IV31, Q8N112, Q8NDY8, Q8QZV0, Q8WV15, Q91WM6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

389 predictions. Top by Δscore:

Variant	Effect	Δscore
7:143286422:AG:A	acceptor_gain	1.0000
7:143286423:GG:G	acceptor_gain	1.0000
7:143286419:CTCA:C	acceptor_loss	0.9900
7:143286421:CAGGG:C	acceptor_loss	0.9900
7:143286422:A:AG	acceptor_gain	0.9900
7:143286422:AGG:A	acceptor_gain	0.9900
7:143286423:G:GG	acceptor_gain	0.9900
7:143286423:GGG:G	acceptor_gain	0.9900
7:143286423:GGGA:G	acceptor_gain	0.9900
7:143286423:GGGAC:G	acceptor_gain	0.9900
7:143283287:A:G	acceptor_gain	0.9700
7:143285365:T:TA	acceptor_gain	0.9700
7:143280046:AGGT:A	donor_loss	0.9600
7:143280048:G:A	donor_loss	0.9600
7:143280049:T:A	donor_loss	0.9600
7:143286089:ATTG:A	acceptor_gain	0.9600
7:143283319:T:A	acceptor_gain	0.9500
7:143285346:A:AG	acceptor_gain	0.9500
7:143285347:G:GG	acceptor_gain	0.9500
7:143285347:GTTGT:G	acceptor_gain	0.9500
7:143286089:ATT:A	acceptor_gain	0.9400
7:143280048:G:GG	donor_gain	0.9300
7:143283286:A:AG	acceptor_gain	0.9300
7:143285347:GTT:G	acceptor_gain	0.9200
7:143285359:T:TA	acceptor_gain	0.9100
7:143286087:ACATT:A	acceptor_gain	0.9000
7:143285444:GG:G	donor_gain	0.8900
7:143285445:GG:G	donor_gain	0.8900
7:143286121:T:TA	acceptor_gain	0.8900
7:143283314:A:AG	acceptor_gain	0.8800

AlphaMissense

1376 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:143286437:T:C	F87L	0.983
7:143286439:T:A	F87L	0.983
7:143286439:T:G	F87L	0.983
7:143286800:T:C	F208L	0.980
7:143286802:T:A	F208L	0.980
7:143286802:T:G	F208L	0.980
7:143286030:G:A	G25R	0.969
7:143286030:G:C	G25R	0.969
7:143286096:G:C	G47R	0.966
7:143286438:T:G	F87C	0.960
7:143286093:G:C	G46R	0.957
7:143286031:G:A	G25E	0.947
7:143286097:G:A	G47D	0.939
7:143286009:T:C	C18R	0.931
7:143286012:T:C	C19R	0.927
7:143286094:G:A	G46D	0.919
7:143286438:T:C	F87S	0.910
7:143286073:C:A	A39D	0.905
7:143286518:T:G	Y114D	0.898
7:143286801:T:G	F208C	0.897
7:143286030:G:T	G25W	0.896
7:143286430:T:A	N84K	0.892
7:143286430:T:G	N84K	0.892
7:143286801:T:C	F208S	0.890
7:143286437:T:A	F87I	0.888
7:143286518:T:C	Y114H	0.884
7:143286761:T:C	Y195H	0.859
7:143286437:T:G	F87V	0.843
7:143286753:C:A	P192H	0.843
7:143286518:T:A	Y114N	0.839

dbSNP variants (sampled 300 via entrez): RS1000525435 (7:143285162 T>G), RS1000593564 (7:143283825 C>A,T), RS1000856564 (7:143287015 A>C), RS1000956468 (7:143285533 G>A), RS1001391691 (7:143284403 TGAA>T), RS1002289718 (7:143287723 A>G), RS1003120910 (7:143284357 T>C), RS1003311207 (7:143284016 G>C), RS1003393955 (7:143287525 C>T), RS1003416108 (7:143284591 G>T), RS1003469824 (7:143285926 T>A,G), RS1003833014 (7:143287794 AC>A), RS1004191626 (7:143284939 C>G,T), RS1004330057 (7:143283199 GT>G), RS1004361276 (7:143283692 CT>C)

Disease associations

OMIM: gene MIM:616524 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	3
Estradiol	affects cotreatment, decreases expression	3
Acetaminophen	decreases expression, affects response to substance	2
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
avobenzone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Progesterone	decreases expression	1

Clinical trials (associated diseases)

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