TMPRSS11A

Summary

TMPRSS11A (transmembrane serine protease 11A, HGNC:27954) is a protein-coding gene on chromosome 4q13.2, encoding Transmembrane protease serine 11A (Q6ZMR5). Probable serine protease which may play a role in cellular senescence.

Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region and plasma membrane.

Source: NCBI Gene 339967 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 69 total
• MANE Select transcript: NM_001114387

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27954
Approved symbol	TMPRSS11A
Name	transmembrane serine protease 11A
Location	4q13.2
Locus type	gene with protein product
Status	Approved
Aliases	ECRG1, HATL1, HESP
Ensembl gene	ENSG00000187054
Ensembl biotype	protein_coding
OMIM	611704
Entrez	339967

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000334830, ENST00000508048, ENST00000513536, ENST00000714500, ENST00000714501, ENST00000714502

RefSeq mRNA: 2 — MANE Select: NM_001114387 NM_001114387, NM_182606

CCDS: CCDS3519, CCDS47065

Canonical transcript exons

ENST00000508048 — 10 exons

Exon	Start	End
ENSE00001339072	67946450	67946571
ENSE00001524188	67944519	67944637
ENSE00002021898	67963383	67963493
ENSE00004024172	67924128	67924166
ENSE00004024173	67909395	67911503
ENSE00004024174	67931993	67932060
ENSE00004024176	67918973	67919232
ENSE00004024179	67929880	67930040
ENSE00004024181	67914588	67914730
ENSE00004024182	67922755	67922926

Expression profiles

Bgee: expression breadth broad, 41 present calls, max score 93.41.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2420 / max 83.5621, expressed in 22 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52321	0.1998	19
52323	0.0239	9
52322	0.0148	6
52320	0.0036	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus mucosa	UBERON:0002469	93.41	gold quality
lower esophagus mucosa	UBERON:0035834	88.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.14	gold quality
vagina	UBERON:0000996	82.27	gold quality
tonsil	UBERON:0002372	70.90	gold quality
esophagus	UBERON:0001043	66.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	57.80	gold quality
ectocervix	UBERON:0012249	54.22	gold quality
uterine cervix	UBERON:0000002	52.04	gold quality
minor salivary gland	UBERON:0001830	49.64	gold quality
bone marrow cell	CL:0002092	48.18	gold quality
saliva-secreting gland	UBERON:0001044	48.09	gold quality
corpus callosum	UBERON:0002336	46.88	silver quality
ventricular zone	UBERON:0003053	44.02	silver quality
urinary bladder	UBERON:0001255	43.87	gold quality
right coronary artery	UBERON:0001625	41.64	silver quality
colonic epithelium	UBERON:0000397	41.40	gold quality
bone marrow	UBERON:0002371	37.88	gold quality
primary visual cortex	UBERON:0002436	37.34	gold quality
ganglionic eminence	UBERON:0004023	37.20	gold quality
granulocyte	CL:0000094	36.83	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	36.65	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
lower esophagus	UBERON:0013473	36.41	gold quality
liver	UBERON:0002107	36.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	36.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.84	gold quality
cortex of kidney	UBERON:0001225	35.76	silver quality
prostate gland	UBERON:0002367	35.74	gold quality
gall bladder	UBERON:0002110	35.02	silver quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting TMPRSS11A, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-3122	99.50	66.33	821

Literature-anchored findings (GeneRIF, showing 10)

• findings indicate that ECRG1 may be a candidate tumor suppressor gene for esophageal cancer involved in cell-cycle control (PMID:17971341)
• DNA polymorphisms in the coding region of ECRG1 are associated with poor outcome after surgical resection in esophageal carcinoma. (PMID:19052822)
• no significant association between single nucleotide polymorphisms Arg/Arg, Arg/Gln and Gln/Gln and survival in oral squamous cell carcinoma (PMID:19394797)
• Data show that ECRG4 interacts directly with ECRG1 to upregulate p21 protein expression, induce cell cycle G1 phase block and inhibit cancer cells proliferation in ESCC. (PMID:21288367)
• A statistically significantly increased risk of ESCC was found to be associated with the ECRG1 Arg/Gln and Gln/Gln genotype. (PMID:21517269)
• Data show that the allele types of ECRG1 were Arg/Arg (54.2%), Arg/Gln (45.8%) and Gln/Gln (0.00%), and the allele types of FGFR4 amino acid 388 were Arg/Arg (8.3%), Arg/Gly (54.2%) and Gly/Gly (37.5%). (PMID:23481570)
• This suggests that substitution of the arginine in the conserved catalytic domain of the ECRG1 protein might reduce its catalytic capacity by impacting its 3-dimensional conformation, thereby causing the genetic susceptibility to ESCC. [review] (PMID:23548972)
• ECRG1 Arg290Gln polymorphism significantly affects the susceptibility but not the prognosis of esophageal squamous cell carcinoma patients in low-risk north Indian population. (PMID:23869757)
• show that TMPRSS11A, another member of the TTSP family, cleaves and activates the influenza A virus (FLUAV) HA and the Middle East respiratory syndrome coronavirus spike protein (MERS-S). (PMID:29976755)
• Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease. (PMID:32675285)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	st14b	ENSDARG00000044655
danio_rerio	st14a	ENSDARG00000061173
danio_rerio		ENSDARG00000062758
danio_rerio	tmprss15	ENSDARG00000079393
mus_musculus	Tmprss11a	ENSMUSG00000072845
rattus_norvegicus	Tmprss11a	ENSRNOG00000046764
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), TMPRSS11B (ENSG00000185873), TMPRSS6 (ENSG00000187045), TMPRSS11F (ENSG00000198092), PRSS41 (ENSG00000215148)

Protein

Protein identifiers

Transmembrane protease serine 11A — Q6ZMR5 (reviewed: Q6ZMR5)

Alternative names: Airway trypsin-like protease 1, Epidermal type-II transmembrane serine protease, Esophageal cancer-susceptibility gene 1 protein

All UniProt accessions (5): A0A0A0MR82, A0AAQ5BI39, A0AAQ5BIA6, Q6ZMR5, H0YAL9

UniProt curated annotations — full annotation on UniProt →

Function. Probable serine protease which may play a role in cellular senescence. Overexpression inhibits cell growth and induce G1 cell cycle arrest.

Subunit / interactions. May interact with ZBTB17.

Subcellular location. Membrane.

Tissue specificity. Expressed in esophagus, liver, colon and lung. Down-regulated in esophagus cancers.

Similarity. Belongs to the peptidase S1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZMR5-2	2	yes
Q6ZMR5-1	1

RefSeq proteins (2): NP_001107859, NP_872412 (=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

Enzyme classification (BRENDA):

• EC 3.4.21.B61 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (24 total): sequence conflict 8, disulfide bond 3, active site 3, topological domain 2, glycosylation site 2, domain 2, chain 1, splice variant 1, sequence variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9P1C	X-RAY DIFFRACTION	2.54

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMR5-F1	87.78	0.63

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): 227 (charge relay system); 272 (charge relay system); 368 (charge relay system)

Disulfide bonds (3): 212–228, 337–353, 364–393

Glycosylation sites (2): 303, 153

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 42 (showing top): chr4q13, GOBP_PROTEIN_MATURATION, WTGAAAT_UNKNOWN, HAND1E47_01, LEIN_CHOROID_PLEXUS_MARKERS, WGGAATGY_TEF1_Q6, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOBP_PROTEIN_PROCESSING, BOSCO_EPITHELIAL_DIFFERENTIATION_MODULE, ICSBP_Q6, GSE13522_CTRL_VS_T_CRUZI_G_STRAIN_INF_SKIN_DN, HMGA1_TARGET_GENES, MIR6867_5P, MIR7_1_3P

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 (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
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

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS11A	FURIN	P09958	613
TMPRSS11A	CTSL	P07711	591
TMPRSS11A	ACE2	Q9BYF1	577
TMPRSS11A	CDKN1A	P38936	497
TMPRSS11A	ANPEP	P15144	462
TMPRSS11A	TOP3B	O95985	455
TMPRSS11A	DPP4	P27487	419
TMPRSS11A	OR5AK2	Q8NH90	411
TMPRSS11A	ECRG4	Q9H1Z8	399
TMPRSS11A	AP2A2	O94973	396
TMPRSS11A	AP2M1	P20172	382
TMPRSS11A	SPINT2	O43291	381
TMPRSS11A	RAB14	P35287	379
TMPRSS11A	CTSB	P07858	375
TMPRSS11A	SPINK7	P58062	373

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TMPRSS11A	S	psi-mi:“MI:0570”(protein cleavage)	0.440
MYC		psi-mi:“MI:0914”(association)	0.350
TMPRSS11A	PAK4	psi-mi:“MI:0914”(association)	0.350
TMPRSS11A	PCDH1	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): SERPINB6 (Affinity Capture-MS), PAK4 (Affinity Capture-MS), ACADL (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), PSG3 (Affinity Capture-MS), TMEM11 (Affinity Capture-MS), TMPRSS11A (Biochemical Activity), ACADL (Affinity Capture-MS), PSG3 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), TMEM11 (Affinity Capture-MS), PAK4 (Affinity Capture-MS), ACE2 (Biochemical Activity), RSPRY1 (Affinity Capture-MS), PAK4 (Affinity Capture-MS)

ESM2 similar proteins: A0A126GUP6, A0A1S4H5M5, A0A1S4H5S2, A6MFK7, B5U2W0, F5HKX0, O60235, O88947, O97366, P00740, P05049, P13582, P15120, P15638, P16292, P16293, P16294, P19540, P21902, P25155, P29598, P49150, P81428, P82807, P83370, P98121, Q14C59, Q27081, Q27083, Q2VG86, Q3UQ41, Q49QW1, Q4QXT9, Q63207, Q6ZMR5, Q7PEV7, Q7QBP4, Q804X6, Q8I6K0, Q8MZM7

Diamond homologs: A0A1S4GMJ4, A6NIE9, A8JUP7, G3V801, O08762, O42207, O60235, P00741, P00745, P00762, P00765, P03951, P05049, P07477, P07478, P0CW18, P15120, P16292, P16295, P19799, P29786, P29787, P35030, P35039, P69525, P79953, Q14B25, Q14BX2, Q14C59, Q1JRP2, Q27081, Q28278, Q28315, Q28412, Q29463, Q2KJ63, Q2VG86, Q5G265, Q5U405, Q6BEA2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

69 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

1954 predictions. Top by Δscore:

Variant	Effect	Δscore
4:67914581:AACTT:A	donor_loss	1.0000
4:67914582:ACTTA:A	donor_loss	1.0000
4:67914583:CTT:C	donor_loss	1.0000
4:67914584:TTA:T	donor_loss	1.0000
4:67914585:T:TG	donor_loss	1.0000
4:67914586:A:AC	donor_gain	1.0000
4:67914586:AC:A	donor_gain	1.0000
4:67914586:ACCCT:A	donor_loss	1.0000
4:67914587:C:CA	donor_loss	1.0000
4:67914587:C:CC	donor_gain	1.0000
4:67914587:CC:C	donor_gain	1.0000
4:67914587:CCCTG:C	donor_gain	1.0000
4:67914726:TTCCC:T	acceptor_gain	1.0000
4:67914728:CCC:C	acceptor_gain	1.0000
4:67914728:CCCCT:C	acceptor_gain	1.0000
4:67914729:CC:C	acceptor_gain	1.0000
4:67914729:CCCT:C	acceptor_gain	1.0000
4:67914730:CC:C	acceptor_gain	1.0000
4:67914731:C:CC	acceptor_gain	1.0000
4:67914731:C:T	acceptor_gain	1.0000
4:67914731:CTTA:C	acceptor_loss	1.0000
4:67914732:T:C	acceptor_gain	1.0000
4:67922748:AACTT:A	donor_loss	1.0000
4:67922749:ACTT:A	donor_loss	1.0000
4:67922751:TTA:T	donor_loss	1.0000
4:67922752:TA:T	donor_loss	1.0000
4:67922753:A:AC	donor_gain	1.0000
4:67922753:ACTT:A	donor_gain	1.0000
4:67922754:C:CA	donor_gain	1.0000
4:67922754:C:T	donor_loss	1.0000

AlphaMissense

2742 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:67914625:C:G	C356S	0.999
4:67914626:A:T	C356S	0.999
4:67914673:C:G	C340S	0.998
4:67914674:A:T	C340S	0.998
4:67918992:A:C	F314L	0.998
4:67918992:A:T	F314L	0.998
4:67918994:A:G	F314L	0.998
4:67911366:C:A	W414C	0.997
4:67911366:C:G	W414C	0.997
4:67911421:C:G	C396S	0.997
4:67911422:A:T	C396S	0.997
4:67911432:C:A	W392C	0.997
4:67911432:C:G	W392C	0.997
4:67914624:A:C	C356W	0.997
4:67914625:C:T	C356Y	0.997
4:67919105:C:G	A277P	0.997
4:67922763:G:C	C231W	0.997
4:67922812:C:G	C215S	0.997
4:67922813:A:T	C215S	0.997
4:67922849:A:G	W203R	0.997
4:67922849:A:T	W203R	0.997
4:67911435:G:C	S391R	0.996
4:67911435:G:T	S391R	0.996
4:67911437:T:G	S391R	0.996
4:67911445:C:T	G388E	0.996
4:67911493:C:A	G372V	0.996
4:67911494:C:A	G372W	0.996
4:67914592:C:G	C367S	0.996
4:67914593:A:T	C367S	0.996
4:67914626:A:G	C356R	0.996

dbSNP variants (sampled 300 via entrez): RS1000001551 (4:67917155 C>G), RS1000018024 (4:67938727 G>A), RS1000122246 (4:67929187 C>T), RS1000159763 (4:67913942 T>C), RS10001655 (4:67942728 G>C,T), RS10001742 (4:67942829 G>A,C), RS1000266738 (4:67954854 A>G), RS1000321624 (4:67935018 GA>G,GAA), RS1000435154 (4:67919911 G>A), RS1000442077 (4:67928906 G>C), RS1000447674 (4:67960885 A>G), RS1000471511 (4:67928594 C>T), RS1000511160 (4:67956016 T>G), RS1000607364 (4:67956399 T>G), RS1000613659 (4:67915847 C>T)

Disease associations

OMIM: gene MIM:611704 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006921_13	Regular attendance at a pub or social club	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009592	social interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases expression	2
bisphenol A	increases methylation	1
glycidyl methacrylate	increases expression	1
sodium arsenite	increases expression	1
monomethylarsonous acid	increases expression	1
Allergens	increases expression	1

Clinical trials (associated diseases)

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