TMPRSS11E

Summary

TMPRSS11E (transmembrane serine protease 11E, HGNC:24465) is a protein-coding gene on chromosome 4q13.2, encoding Transmembrane protease serine 11E (Q9UL52). Serine protease which possesses both gelatinolytic and caseinolytic activities.

Predicted to enable serine-type peptidase activity. Involved in cognition. Predicted to be located in extracellular region and membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 28983 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_014058

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24465
Approved symbol	TMPRSS11E
Name	transmembrane serine protease 11E
Location	4q13.2
Locus type	gene with protein product
Status	Approved
Aliases	DESC1
Ensembl gene	ENSG00000087128
Ensembl biotype	protein_coding
OMIM	610399
Entrez	28983

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000305363, ENST00000510647

RefSeq mRNA: 1 — MANE Select: NM_014058 NM_014058

CCDS: CCDS33993

Canonical transcript exons

ENST00000305363 — 10 exons

Exon	Start	End
ENSE00001596784	68447463	68447523
ENSE00001660015	68478849	68478991
ENSE00001690619	68471460	68471623
ENSE00001714583	68477369	68477628
ENSE00001740194	68468879	68468946
ENSE00001760089	68496643	68497604
ENSE00001784863	68466631	68466752
ENSE00001789388	68461821	68461945
ENSE00003486034	68474723	68474761
ENSE00003687880	68476261	68476438

Expression profiles

Bgee: expression breadth broad, 94 present calls, max score 99.15.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7045 / max 290.1844, expressed in 230 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47826	1.3887	202
47825	0.3159	85

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.15	gold quality
esophagus mucosa	UBERON:0002469	96.57	gold quality
vagina	UBERON:0000996	85.81	gold quality
minor salivary gland	UBERON:0001830	84.91	gold quality
saliva-secreting gland	UBERON:0001044	84.74	gold quality
tonsil	UBERON:0002372	81.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.17	gold quality
esophagus	UBERON:0001043	72.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	70.19	gold quality
skin of abdomen	UBERON:0001416	64.59	gold quality
zone of skin	UBERON:0000014	62.87	gold quality
skin of leg	UBERON:0001511	61.50	gold quality
islet of Langerhans	UBERON:0000006	61.14	gold quality
urinary bladder	UBERON:0001255	60.93	gold quality
ectocervix	UBERON:0012249	60.65	gold quality
prostate gland	UBERON:0002367	57.66	gold quality
uterine cervix	UBERON:0000002	57.60	gold quality
pancreas	UBERON:0001264	53.87	gold quality
body of pancreas	UBERON:0001150	50.29	gold quality
endocervix	UBERON:0000458	46.62	gold quality
lower esophagus	UBERON:0013473	44.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	44.82	gold quality
right coronary artery	UBERON:0001625	44.49	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	43.79	gold quality
fallopian tube	UBERON:0003889	43.63	gold quality
left uterine tube	UBERON:0001303	42.68	gold quality
right lobe of liver	UBERON:0001114	42.58	gold quality
bone marrow cell	CL:0002092	41.67	gold quality
sural nerve	UBERON:0015488	41.11	silver quality
liver	UBERON:0002107	40.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	182.83
E-CURD-114	yes	11.87
E-ANND-3	yes	4.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting TMPRSS11E, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-6885-3P	99.75	70.36	3187

Literature-anchored findings (GeneRIF, showing 4)

• The domain of DESC1 exhibits a trypsin-like serine proteinase fold with a thrombin-like S1 pocket, a urokinase-type plasminogen activator-type S2 pocket, to accept small residues, and an open hydrophobic S3/S4 cavity to accept large hydrophobic residues. (PMID:17388811)
• study demonstrates that two cellular serine proteases, DESC1 and MSPL, activate influenza viruses and emerging coronaviruses in cell culture and, because of their expression in human lung tissue, might promote viral spread in the infected host (PMID:25122802)
• DESC1 may suppress esophageal squamous cell carcinoma development by sensitizing cells to apoptosis under an apoptotic stimulus through downregulating the EGFR/AKT signaling pathway. (PMID:26856390)
• Elevated expression of the membrane-anchored serine protease TMPRSS11E in NSCLC progression. (PMID:35951670)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	st14b	ENSDARG00000044655
danio_rerio	st14a	ENSDARG00000061173
danio_rerio	tmprss15	ENSDARG00000079393
mus_musculus	Tmprss11e	ENSMUSG00000054537
rattus_norvegicus	Tmprss11e	ENSRNOG00000022255
drosophila_melanogaster	Sb	FBGN0003319
drosophila_melanogaster	CG1632	FBGN0030027
drosophila_melanogaster	CG10587	FBGN0037039
drosophila_melanogaster	CG17242	FBGN0250841

Paralogs (17): PRSS22 (ENSG00000005001), PRSS21 (ENSG00000007038), HPN (ENSG00000105707), TMPRSS13 (ENSG00000137747), ST14 (ENSG00000149418), TMPRSS11D (ENSG00000153802), TMPRSS15 (ENSG00000154646), TMPRSS3 (ENSG00000160183), TMPRSS5 (ENSG00000166682), TMPRSS7 (ENSG00000176040), TMPRSS9 (ENSG00000178297), TMPRSS2 (ENSG00000184012), TMPRSS11B (ENSG00000185873), TMPRSS6 (ENSG00000187045), TMPRSS11A (ENSG00000187054), TMPRSS11F (ENSG00000198092), PRSS41 (ENSG00000215148)

Protein

Protein identifiers

Transmembrane protease serine 11E — Q9UL52 (reviewed: Q9UL52)

Alternative names: Serine protease DESC1, Transmembrane protease serine 11E2

All UniProt accessions (2): Q9UL52, H0Y9G7

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease which possesses both gelatinolytic and caseinolytic activities. Shows a preference for Arg in the P1 position.

Subunit / interactions. Forms a heterodimer with SERPINA5 and SERPINE1.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Expression can only be detected in tissues derived from the head and neck, and in skin, prostate and testis.

Post-translational modifications. N-glycosylated.

Activity regulation. Inhibited by SERPINA5.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_054777* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000082	SEA_dom	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR017329	Pept_S1A_HAT/DESC1	Family
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR036364	SEA_dom_sf	Homologous_superfamily
IPR043504

Pfam: PF00089, PF01390

UniProt features (40 total): strand 15, helix 5, disulfide bond 4, glycosylation site 3, active site 3, chain 2, topological domain 2, domain 2, sequence variant 1, sequence conflict 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2OQ5	X-RAY DIFFRACTION	1.61

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL52-F1	89.93	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 232 (charge relay system); 277 (charge relay system); 373 (charge relay system)

Disulfide bonds (4): 177–297, 217–233, 342–358, 369–398

Glycosylation sites (3): 75, 166, 223

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 61 (showing top): GOBP_COGNITION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, ONDER_CDH1_TARGETS_3_DN, chr4q13, GOBP_PROTEIN_MATURATION, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, RICKMAN_HEAD_AND_NECK_CANCER_E, GOBP_PROTEIN_PROCESSING, BOSCO_EPITHELIAL_DIFFERENTIATION_MODULE, MIR944, MIR6885_3P, MIR519E_5P, MIR515_5P, MIR4778_3P

GO Biological Process (2): proteolysis (GO:0006508), cognition (GO:0050890)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (3): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein metabolic process	1
nervous system process	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS11E	SERPINA5	P05154	833
TMPRSS11E	SERPINE1	P05121	607
TMPRSS11E	ACE2	Q9BYF1	419
TMPRSS11E	SPINT1	O43278	380
TMPRSS11E	OR5M3	Q8NGP4	363
TMPRSS11E	RIPOR3	Q96MK2	349
TMPRSS11E	SLC6A14	Q9UN76	344
TMPRSS11E	TBC1D22B	Q9NU19	343
TMPRSS11E	TMEM117	Q9H0C3	326
TMPRSS11E	STK33	Q9BYT3	326
TMPRSS11E	SH2D7	A6NKC9	325
TMPRSS11E	HRC	P23327	316
TMPRSS11E	SPINT2	O43291	311
TMPRSS11E	PYROXD2	Q8N2H3	298
TMPRSS11E	UNC79	Q9P2D8	291

IntAct

7 interactions, top by confidence:

A	B	Type	Score
MEOX2	TMPRSS11E	psi-mi:“MI:0915”(physical association)	0.560
SBK2	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
TMPRSS11E	RAB4A	psi-mi:“MI:0914”(association)	0.350
TMPRSS11E	SRC	psi-mi:“MI:0914”(association)	0.350
TMPRSS11E	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): MEOX2 (Two-hybrid), DBNL (Affinity Capture-MS), GATM (Affinity Capture-MS), TM2D3 (Affinity Capture-MS), SYT6 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), RAB4A (Affinity Capture-MS), ACOT1 (Affinity Capture-MS), KPRP (Affinity Capture-MS), SRC (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), TMPRSS11E (Affinity Capture-MS)

ESM2 similar proteins: A0A182C2Z2, A0A1S4GMJ4, A6MFK8, B5G6G5, O15393, O60235, O70244, O96900, P00750, P05156, P11214, P19637, P25723, P29598, P79953, P81428, P82807, P83370, P86091, P97435, P98072, P98073, P98074, P98119, P98121, Q05589, Q14C59, Q17800, Q20176, Q4QXT9, Q58L93, Q58L94, Q5QSK2, Q5R5A4, Q5R8J0, Q61129, Q66TN7, Q6DIV5, Q6IE14, Q6ZMR5

Diamond homologs: A0A1B0GVH4, A1L453, A2VE36, E5RG02, F2YMG0, O35205, O35453, O60235, O97370, P03952, P05981, P06868, P08001, P08709, P10323, P14272, P19236, P20231, P22457, P23578, P26262, P29293, P29786, P35035, P35036, P35038, P35039, P35040, P35041, P39675, P49275, P49864, P50342, P69526, P70375, P83748, P98139, Q05511, Q14B25, Q14BX2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1324 predictions. Top by Δscore:

Variant	Effect	Δscore
4:68466625:TTGTA:T	acceptor_loss	1.0000
4:68466626:TGTA:T	acceptor_loss	1.0000
4:68466627:GTAGA:G	acceptor_loss	1.0000
4:68466628:TA:T	acceptor_loss	1.0000
4:68466629:A:AG	acceptor_gain	1.0000
4:68466630:G:A	acceptor_loss	1.0000
4:68466630:G:GG	acceptor_gain	1.0000
4:68466749:AATGG:A	donor_loss	1.0000
4:68466750:ATG:A	donor_gain	1.0000
4:68466750:ATGG:A	donor_loss	1.0000
4:68466751:TGG:T	donor_loss	1.0000
4:68466752:GGT:G	donor_loss	1.0000
4:68466753:G:GG	donor_gain	1.0000
4:68466753:GTAA:G	donor_loss	1.0000
4:68466754:T:G	donor_loss	1.0000
4:68471624:G:GG	donor_gain	1.0000
4:68474758:CATT:C	donor_gain	1.0000
4:68474762:G:GG	donor_gain	1.0000
4:68476255:TTGCA:T	acceptor_loss	1.0000
4:68476256:TGCAG:T	acceptor_loss	1.0000
4:68476257:GCAG:G	acceptor_loss	1.0000
4:68476258:CAG:C	acceptor_loss	1.0000
4:68477625:GATG:G	donor_gain	1.0000
4:68477653:G:GG	donor_gain	1.0000
4:68477660:T:G	donor_gain	1.0000
4:68478847:A:AG	acceptor_gain	1.0000
4:68478847:A:AT	acceptor_loss	1.0000
4:68478848:G:GG	acceptor_gain	1.0000
4:68478990:AGGT:A	donor_loss	1.0000
4:68478991:G:GT	donor_loss	1.0000

AlphaMissense

2769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:68476416:A:C	S229R	0.998
4:68476418:T:A	S229R	0.998
4:68476418:T:G	S229R	0.998
4:68476344:T:A	W205R	0.997
4:68476344:T:C	W205R	0.997
4:68478953:T:A	C358S	0.997
4:68478954:G:C	C358S	0.997
4:68478986:T:A	C369S	0.996
4:68478987:G:C	C369S	0.996
4:68496709:A:C	S393R	0.996
4:68496711:C:A	S393R	0.996
4:68496711:C:G	S393R	0.996
4:68476346:G:C	W205C	0.995
4:68476346:G:T	W205C	0.995
4:68476380:T:A	C217S	0.995
4:68476381:G:C	C217S	0.995
4:68476430:T:G	C233W	0.995
4:68477607:T:C	F316L	0.995
4:68477609:T:A	F316L	0.995
4:68477609:T:G	F316L	0.995
4:68478905:T:A	C342S	0.995
4:68478906:G:C	C342S	0.995
4:68496662:T:C	L377P	0.995
4:68496780:G:C	W416C	0.995
4:68496780:G:T	W416C	0.995
4:68496714:G:C	W394C	0.994
4:68496714:G:T	W394C	0.994
4:68496724:T:A	C398S	0.994
4:68496725:G:C	C398S	0.994
4:68476428:T:A	C233S	0.993

dbSNP variants (sampled 300 via entrez): RS1000091751 (4:68491483 A>G), RS1000113393 (4:68485920 T>G), RS1000120871 (4:68476094 A>C), RS1000181556 (4:68479362 G>A), RS1000208042 (4:68479586 C>T), RS1000360866 (4:68472823 T>C), RS1000395633 (4:68492100 C>A,G,T), RS1000446483 (4:68485605 GT>G), RS1000486279 (4:68467044 G>A), RS1000680107 (4:68480262 G>A), RS1000726099 (4:68474666 G>A), RS1000794133 (4:68473095 G>A), RS1000820313 (4:68468713 G>A), RS1000849465 (4:68469237 A>C), RS1001097866 (4:68474361 G>A,C)

Disease associations

OMIM: gene MIM:610399 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST004602_151	Mean corpuscular volume	6.000000e-09
GCST006611_104	HDL cholesterol	2.000000e-10
GCST006612_35	LDL cholesterol	2.000000e-16
GCST006614_26	Total cholesterol levels	1.000000e-26
GCST007931_60	Medication use (HMG CoA reductase inhibitors)	8.000000e-09
GCST009733_197	Urinary metabolite levels in chronic kidney disease	4.000000e-93
GCST009733_198	Urinary metabolite levels in chronic kidney disease	2.000000e-27
GCST009733_237	Urinary metabolite levels in chronic kidney disease	6.000000e-24
GCST010241_131	Apolipoprotein A1 levels	5.000000e-24
GCST010242_38	HDL cholesterol levels	4.000000e-15
GCST010243_27	Apolipoprotein B levels	1.000000e-20
GCST010245_132	LDL cholesterol levels	7.000000e-24
GCST011346_18	Total cholesterol levels	6.000000e-09
GCST011347_20	Low density lipoprotein cholesterol levels	4.000000e-08
GCST012020_278	Serum metabolite levels	1.000000e-28
GCST012020_279	Serum metabolite levels	2.000000e-13
GCST012020_280	Serum metabolite levels	1.000000e-41
GCST012020_281	Serum metabolite levels	8.000000e-31
GCST012020_282	Serum metabolite levels	2.000000e-13
GCST012020_283	Serum metabolite levels	2.000000e-12
GCST012020_284	Serum metabolite levels	1.000000e-10
GCST90002392_656	Mean corpuscular volume	5.000000e-10
GCST90011900_95	Serum alkaline phosphatase levels	2.000000e-25
GCST90013406_267	Liver enzyme levels (alkaline phosphatase)	1.000000e-50

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0005116	urinary metabolite measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2168047	TMPRSS11E		0.00	0

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	5
trichostatin A	increases expression	2
entinostat	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	affects cotreatment, decreases expression	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	increases expression	1
Methapyrilene	increases methylation	1
Nickel	decreases expression	1
Silicon Dioxide	increases expression	1
Dihydrotestosterone	increases expression	1
Testosterone	affects cotreatment, decreases expression	1
Isotretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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