TMPRSS11B

Summary

TMPRSS11B (transmembrane serine protease 11B, HGNC:25398) is a protein-coding gene on chromosome 4q13.2, encoding Transmembrane protease serine 11B (Q86T26). Serine protease.

Enables serine-type peptidase activity. Predicted to be involved in proteolysis. Located in plasma membrane.

Source: NCBI Gene 132724 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_182502

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25398
Approved symbol	TMPRSS11B
Name	transmembrane serine protease 11B
Location	4q13.2
Locus type	gene with protein product
Status	Approved
Aliases	HATL5
Ensembl gene	ENSG00000185873
Ensembl biotype	protein_coding
Entrez	132724

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 retained_intron, 1 protein_coding

ENST00000332644, ENST00000502365, ENST00000510856

RefSeq mRNA: 1 — MANE Select: NM_182502 NM_182502

CCDS: CCDS3521

Canonical transcript exons

ENST00000332644 — 10 exons

Exon	Start	End
ENSE00001310512	68226653	68228072
ENSE00001340982	68229257	68229516
ENSE00001340983	68231203	68231380
ENSE00001340985	68232378	68232416
ENSE00002034657	68245551	68245694
ENSE00003536600	68241689	68241804
ENSE00003543224	68236002	68236069
ENSE00003561513	68236151	68236266
ENSE00003602909	68228742	68228884
ENSE00003629864	68234463	68234623

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 99.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.2619 / max 657.3806, expressed in 22 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52329	1.2619	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.74	gold quality
pharyngeal mucosa	UBERON:0000355	99.59	gold quality
oral cavity	UBERON:0000167	99.31	gold quality
body of tongue	UBERON:0011876	98.77	gold quality
esophagus mucosa	UBERON:0002469	97.83	gold quality
esophagus squamous epithelium	UBERON:0006920	97.45	gold quality
tongue	UBERON:0001723	95.79	gold quality
gingiva	UBERON:0001828	95.10	gold quality
gingival epithelium	UBERON:0001949	93.78	gold quality
superior surface of tongue	UBERON:0007371	91.97	gold quality
amniotic fluid	UBERON:0000173	89.54	gold quality
vagina	UBERON:0000996	85.04	gold quality
sperm	CL:0000019	84.36	gold quality
buccal mucosa cell	CL:0002336	81.15	gold quality
tonsil	UBERON:0002372	77.89	gold quality
esophagus	UBERON:0001043	77.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.60	gold quality
palpebral conjunctiva	UBERON:0001812	74.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.49	gold quality
epithelium of nasopharynx	UBERON:0001951	70.70	gold quality
ectocervix	UBERON:0012249	68.19	gold quality
mouth mucosa	UBERON:0003729	67.32	gold quality
nasal cavity epithelium	UBERON:0005384	65.57	silver quality
minor salivary gland	UBERON:0001830	63.02	gold quality
uterine cervix	UBERON:0000002	62.79	gold quality
saliva-secreting gland	UBERON:0001044	57.37	gold quality
right coronary artery	UBERON:0001625	54.69	gold quality
lower esophagus	UBERON:0013473	54.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	54.08	gold quality
left uterine tube	UBERON:0001303	51.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	12876.20
E-ANND-3	yes	4.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting TMPRSS11B, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AG	99.77	69.25	1492

Literature-anchored findings (GeneRIF, showing 2)

• Data indicate that TMPRSS11b (BC126195), encoding human airway trypsin-like protease 5 (HATL5), is localized on the cell surface of differentiated epithelial cells in the stratified squamous epithelia of cervix, esophagus, and oral cavity. (PMID:24498351)
• These findings establish an oncogenic role for TMPRSS11B and provide support for the development of therapies that target this enzyme at the surface of cancer cells. (PMID:30463017)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	st14b	ENSDARG00000044655
danio_rerio	st14a	ENSDARG00000061173
danio_rerio		ENSDARG00000062758
danio_rerio	tmprss15	ENSDARG00000079393
drosophila_melanogaster	Sb	FBGN0003319
drosophila_melanogaster	CG1632	FBGN0030027
drosophila_melanogaster	CG10587	FBGN0037039
drosophila_melanogaster	CG17242	FBGN0250841

Paralogs (17): PRSS22 (ENSG00000005001), PRSS21 (ENSG00000007038), TMPRSS11E (ENSG00000087128), HPN (ENSG00000105707), TMPRSS13 (ENSG00000137747), ST14 (ENSG00000149418), TMPRSS11D (ENSG00000153802), TMPRSS15 (ENSG00000154646), TMPRSS3 (ENSG00000160183), TMPRSS5 (ENSG00000166682), TMPRSS7 (ENSG00000176040), TMPRSS9 (ENSG00000178297), TMPRSS2 (ENSG00000184012), TMPRSS6 (ENSG00000187045), TMPRSS11A (ENSG00000187054), TMPRSS11F (ENSG00000198092), PRSS41 (ENSG00000215148)

Protein

Protein identifiers

Transmembrane protease serine 11B — Q86T26 (reviewed: Q86T26)

Alternative names: Airway trypsin-like protease 5

All UniProt accessions (1): Q86T26

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease.

Subcellular location. Cell membrane.

Activity regulation. Inhibited by aprotinin, leupeptin, benzamidine, SERPINA1, SPINT1 and SPINT2.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_872308* (*=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
IPR036364	SEA_dom_sf	Homologous_superfamily
IPR043504

Pfam: PF00089, PF01390

UniProt features (18 total): glycosylation site 3, disulfide bond 3, sequence variant 3, active site 3, topological domain 2, domain 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86T26-F1	91.68	0.81

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): 225 (charge relay system); 270 (charge relay system); 366 (charge relay system)

Disulfide bonds (3): 210–226, 335–351, 362–391

Glycosylation sites (3): 107, 315, 72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, chr4q13, GOBP_PROTEIN_MATURATION, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, RICKMAN_HEAD_AND_NECK_CANCER_E, GOBP_PROTEIN_PROCESSING, RAO_BOUND_BY_SALL4_ISOFORM_A, BOSCO_EPITHELIAL_DIFFERENTIATION_MODULE, MIR3662, MIR374A_5P, MIR374B_5P, MIR4427, MIR4325

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (4): serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (4): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), extracellular region (GO:0005576), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS11B	CRNN	Q9UBG3	474
TMPRSS11B	DPP4	P27487	407
TMPRSS11B	SCEL	O95171	403
TMPRSS11B	ANPEP	P15144	402
TMPRSS11B	TMPRSS12	Q86WS5	390
TMPRSS11B	RAB14	P35287	350
TMPRSS11B	RPS15	P11174	348
TMPRSS11B	ACE2	Q9BYF1	339
TMPRSS11B	FAM3D	Q96BQ1	331
TMPRSS11B	KRTDAP	P60985	324
TMPRSS11B	CHMP2A	O43633	321
TMPRSS11B	AADACL2	Q6P093	321
TMPRSS11B	CRISP3	P54108	316
TMPRSS11B	VSIG10L	Q86VR7	313
TMPRSS11B	SPINK7	P58062	310

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TMPRSS11B		psi-mi:“MI:0914”(association)	0.350
TMPRSS11B	ADAM10	psi-mi:“MI:0914”(association)	0.350
TMPRSS11B	SCAMP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (516): EPHA7 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), TMEM8A (Affinity Capture-MS), SEMA4F (Affinity Capture-MS), ADAMTS2 (Affinity Capture-MS), FZD2 (Affinity Capture-MS), GLRB (Affinity Capture-MS), DCBLD2 (Affinity Capture-MS), DHFRL1 (Affinity Capture-MS), EDEM2 (Affinity Capture-MS), HLA-A (Affinity Capture-MS), TMEM67 (Affinity Capture-MS), BACE2 (Affinity Capture-MS), SLC16A10 (Affinity Capture-MS), CTAGE5 (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: A0A126GUP6, A0A182C2Z2, A0A1S4H5M5, A8JUP7, B5U2W0, B7YZU2, F5HKX0, O15393, O35453, O60235, O60259, O97366, P00774, P03951, P03952, P05049, P05981, P08419, P09871, P10323, P13582, P14272, P21902, P23578, P25155, P26262, P28175, P29293, P31394, P33587, P35035, P35036, P35037, P35039, P35041, P35045, P35046, P35047, P40313, P48038

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1440 predictions. Top by Δscore:

Variant	Effect	Δscore
4:68228069:CATT:C	acceptor_gain	1.0000
4:68228737:CATA:C	donor_loss	1.0000
4:68228739:TAC:T	donor_loss	1.0000
4:68228740:A:T	donor_loss	1.0000
4:68228741:C:CG	donor_loss	1.0000
4:68232372:A:C	donor_gain	1.0000
4:68232376:A:AC	donor_gain	1.0000
4:68232377:C:CC	donor_gain	1.0000
4:68232415:TT:T	acceptor_gain	1.0000
4:68232415:TTC:T	acceptor_loss	1.0000
4:68232416:TCTG:T	acceptor_loss	1.0000
4:68232417:C:CC	acceptor_gain	1.0000
4:68232417:C:T	acceptor_loss	1.0000
4:68232418:T:A	acceptor_loss	1.0000
4:68232423:G:C	acceptor_gain	1.0000
4:68232423:G:GC	acceptor_gain	1.0000
4:68236000:A:AC	donor_gain	1.0000
4:68236001:C:CC	donor_gain	1.0000
4:68236067:CAT:C	acceptor_gain	1.0000
4:68236070:C:CC	acceptor_gain	1.0000
4:68236146:TTTA:T	donor_loss	1.0000
4:68236147:TTAC:T	donor_loss	1.0000
4:68236148:TACCT:T	donor_loss	1.0000
4:68236149:A:T	donor_loss	1.0000
4:68241683:ACTC:A	donor_loss	1.0000
4:68241684:CTC:C	donor_loss	1.0000
4:68241686:CAC:C	donor_loss	1.0000
4:68241686:CACCA:C	donor_gain	1.0000
4:68241687:A:AC	donor_gain	1.0000
4:68241687:A:AT	donor_loss	1.0000

AlphaMissense

2763 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:68227935:C:A	W409C	0.946
4:68227935:C:G	W409C	0.946
4:68229276:C:A	W309C	0.943
4:68229276:C:G	W309C	0.943
4:68228004:G:C	S386R	0.942
4:68228004:G:T	S386R	0.942
4:68228006:T:G	S386R	0.942
4:68231208:A:C	F227L	0.929
4:68231208:A:T	F227L	0.929
4:68231210:A:G	F227L	0.929
4:68228779:C:G	C351S	0.928
4:68228780:A:T	C351S	0.928
4:68231295:C:A	W198C	0.927
4:68231295:C:G	W198C	0.927
4:68228827:C:G	C335S	0.921
4:68228828:A:T	C335S	0.921
4:68231286:G:C	S201R	0.920
4:68231286:G:T	S201R	0.920
4:68231288:T:G	S201R	0.920
4:68231297:A:G	W198R	0.915
4:68231297:A:T	W198R	0.915
4:68229278:A:G	W309R	0.904
4:68229278:A:T	W309R	0.904
4:68234581:G:C	F117L	0.901
4:68234581:G:T	F117L	0.901
4:68234583:A:G	F117L	0.901
4:68229389:C:G	A272P	0.900
4:68227937:A:G	W409R	0.895
4:68227937:A:T	W409R	0.895
4:68231234:A:G	W219R	0.891

dbSNP variants (sampled 300 via entrez): RS1000045419 (4:68243220 C>A), RS1000073285 (4:68238540 T>A,C), RS1000100470 (4:68238624 G>A,T), RS10001898 (4:68230676 T>C), RS1000351397 (4:68245207 T>C), RS1000492837 (4:68231359 T>C), RS1000570496 (4:68232187 T>A), RS10006271 (4:68247227 T>C), RS10006952 (4:68232875 C>T), RS1000775720 (4:68231085 T>C), RS10009365 (4:68240976 G>A), RS1001312896 (4:68241450 C>T), RS10014409 (4:68247542 G>A,T), RS1001777527 (4:68239772 G>T), RS10017863 (4:68231976 T>C)

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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	decreases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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