TMPRSS11F

Summary

TMPRSS11F (transmembrane serine protease 11F, HGNC:29994) is a protein-coding gene on chromosome 4q13.2, encoding Transmembrane protease serine 11F (Q6ZWK6). Probable serine protease.

Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within establishment of skin barrier. Located in cell surface.

Source: NCBI Gene 389208 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_207407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29994
Approved symbol	TMPRSS11F
Name	transmembrane serine protease 11F
Location	4q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16046, HATL4
Ensembl gene	ENSG00000198092
Ensembl biotype	protein_coding
Entrez	389208

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000356291

RefSeq mRNA: 1 — MANE Select: NM_207407 NM_207407

CCDS: CCDS3520

Canonical transcript exons

ENST00000356291 — 10 exons

Exon	Start	End
ENSE00001400809	68073942	68074009
ENSE00001401666	68072323	68072486
ENSE00001403735	68069969	68070007
ENSE00001404332	68053198	68054067
ENSE00001406908	68068618	68068819
ENSE00001408488	68059326	68059468
ENSE00001410103	68064685	68064944
ENSE00001432020	68098887	68099038
ENSE00001432599	68129810	68129869
ENSE00001434065	68090523	68090641

Expression profiles

Bgee: expression breadth broad, 34 present calls, max score 80.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0687 / max 12.0973, expressed in 27 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52325	0.0687	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	80.29	gold quality
esophagus mucosa	UBERON:0002469	80.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.55	gold quality
skin of leg	UBERON:0001511	70.63	gold quality
zone of skin	UBERON:0000014	70.33	gold quality
skin of abdomen	UBERON:0001416	69.52	gold quality
vagina	UBERON:0000996	67.75	gold quality
tonsil	UBERON:0002372	59.43	gold quality
esophagus	UBERON:0001043	55.85	gold quality
placenta	UBERON:0001987	46.51	gold quality
ectocervix	UBERON:0012249	46.26	gold quality
uterine cervix	UBERON:0000002	43.14	gold quality
bone marrow cell	CL:0002092	42.03	gold quality
colonic epithelium	UBERON:0000397	41.63	gold quality
primary visual cortex	UBERON:0002436	41.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	40.30	gold quality
ventricular zone	UBERON:0003053	40.13	gold quality
stromal cell of endometrium	CL:0002255	39.12	gold quality
granulocyte	CL:0000094	38.95	gold quality
superior frontal gyrus	UBERON:0002661	38.82	gold quality
skeletal muscle tissue	UBERON:0001134	38.81	silver quality
minor salivary gland	UBERON:0001830	38.42	gold quality
sural nerve	UBERON:0015488	37.92	gold quality
saliva-secreting gland	UBERON:0001044	37.59	gold quality
ganglionic eminence	UBERON:0004023	37.26	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow	UBERON:0002371	35.85	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.53	gold quality
endometrium	UBERON:0001295	34.96	gold quality
corpus callosum	UBERON:0002336	34.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting TMPRSS11F, 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-3646	100.00	73.56	5283
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-516A-3P	99.46	67.96	1378

Literature-anchored findings (GeneRIF, showing 2)

• Study reveals a role of HAT-L4 in the epidermal barrier function to prevent body fluid loss, providing another example of cell membrane-bound serine proteases in epidermal development and function. (PMID:28338078)
• Results indicate that ectopic HAT-L4 expression is a pathological mechanism in neutrophils and monocytes from acute myeloid leukemia (AML) and that HAT-L4 may be used as a cell surface marker for AML blast detection. (PMID:30843660)

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	Tmprss11f	ENSMUSG00000048764
rattus_norvegicus	Tmprss11f	ENSRNOG00000002005
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), TMPRSS11A (ENSG00000187054), PRSS41 (ENSG00000215148)

Protein

Protein identifiers

Transmembrane protease serine 11F — Q6ZWK6 (reviewed: Q6ZWK6)

Alternative names: Airway trypsin-like protease 4

All UniProt accessions (1): Q6ZWK6

UniProt curated annotations — full annotation on UniProt →

Function. Probable serine protease.

Subcellular location. Membrane.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_997290* (*=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 (15 total): disulfide bond 3, active site 3, topological domain 2, sequence variant 2, domain 2, chain 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZWK6-F1	87.70	0.61

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): 248 (charge relay system); 293 (charge relay system); 389 (charge relay system)

Disulfide bonds (3): 358–374, 385–413, 233–249

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, CCAWYNNGAAR_UNKNOWN, GOCC_CELL_SURFACE, chr4q13, GOBP_PROTEIN_MATURATION, TGANTCA_AP1_C, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_SKIN_DEVELOPMENT, TAL1BETAE47_01, TGGAAA_NFAT_Q4_01, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, TAL1BETAITF2_01, GOBP_PROTEIN_PROCESSING, GREB1_TARGET_GENES

GO Biological Process (2): proteolysis (GO:0006508), establishment of skin barrier (GO:0061436)

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): extracellular region (GO:0005576), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein metabolic process	1
skin epidermis development	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

506 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS11F	RPS15	P11174	366
TMPRSS11F	AGRN	O00468	328
TMPRSS11F	DNAJB14	Q8TBM8	321
TMPRSS11F	RIT2	Q99578	319
TMPRSS11F	TCP11	Q8WWU5	316
TMPRSS11F	TSPYL1	Q9H0U9	312
TMPRSS11F	ADAM32	Q8TC27	307
TMPRSS11F	ADAM30	Q9UKF2	301
TMPRSS11F	MARCHF4	Q9P2E8	290
TMPRSS11F	M9MMK7	M9MMK7	290
TMPRSS11F	PGLYRP3	Q96LB9	287
TMPRSS11F	TESK1	Q15569	285
TMPRSS11F	ADAD1	Q96M93	284
TMPRSS11F	SEMG2	Q02383	279
TMPRSS11F	SLC6A18	Q96N87	271

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TMPRSS11F	VDAC1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): TMPRSS11F (Proximity Label-MS), EEF2 (Cross-Linking-MS (XL-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: 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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2241 predictions. Top by Δscore:

Variant	Effect	Δscore
4:68059321:CTTA:C	donor_loss	1.0000
4:68059322:TTA:T	donor_loss	1.0000
4:68059323:TACC:T	donor_loss	1.0000
4:68059324:A:C	donor_loss	1.0000
4:68059325:CCTTA:C	donor_gain	1.0000
4:68059468:CCTAT:C	acceptor_gain	1.0000
4:68059469:C:CC	acceptor_gain	1.0000
4:68059472:T:TC	acceptor_gain	1.0000
4:68059477:CAAA:C	acceptor_gain	1.0000
4:68059480:A:AC	acceptor_gain	1.0000
4:68059480:A:C	acceptor_gain	1.0000
4:68069967:A:AC	donor_gain	1.0000
4:68069968:C:CC	donor_gain	1.0000
4:68069968:CGA:C	donor_gain	1.0000
4:68072321:A:AC	donor_gain	1.0000
4:68072322:C:CC	donor_gain	1.0000
4:68072322:CG:C	donor_gain	1.0000
4:68072482:CTGGA:C	acceptor_gain	1.0000
4:68072483:TGGA:T	acceptor_gain	1.0000
4:68072487:C:CC	acceptor_gain	1.0000
4:68090516:AGCTT:A	donor_loss	1.0000
4:68090517:GCTTA:G	donor_loss	1.0000
4:68090518:CTT:C	donor_loss	1.0000
4:68090519:TTACC:T	donor_loss	1.0000
4:68090520:TACCA:T	donor_loss	1.0000
4:68090521:ACCAT:A	donor_loss	1.0000
4:68090522:CCATT:C	donor_gain	1.0000
4:68098885:AC:A	donor_gain	1.0000
4:68098886:CC:C	donor_gain	1.0000
4:68099034:CAGGT:C	acceptor_gain	1.0000

AlphaMissense

2874 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:68059411:C:G	C358S	0.998
4:68059412:A:T	C358S	0.998
4:68053933:C:A	W431C	0.997
4:68053933:C:G	W431C	0.997
4:68059363:C:G	C374S	0.997
4:68059364:A:T	C374S	0.997
4:68064704:A:C	F332L	0.997
4:68064704:A:T	F332L	0.997
4:68064706:A:G	F332L	0.997
4:68054048:A:G	L393P	0.996
4:68064817:C:G	A295P	0.996
4:68068626:G:C	C249W	0.996
4:68068675:C:G	C233S	0.996
4:68068676:A:T	C233S	0.996
4:68068715:A:G	W220R	0.996
4:68068715:A:T	W220R	0.996
4:68068721:A:G	W218R	0.996
4:68068721:A:T	W218R	0.996
4:68054002:A:C	S408R	0.995
4:68054002:A:T	S408R	0.995
4:68054004:T:G	S408R	0.995
4:68059330:C:G	C385S	0.995
4:68059331:A:T	C385S	0.995
4:68059362:A:C	C374W	0.995
4:68059363:C:T	C374Y	0.995
4:68059364:A:G	C374R	0.995
4:68059411:C:T	C358Y	0.995
4:68059412:A:G	C358R	0.995
4:68064822:T:A	D293V	0.995
4:68053999:C:A	W409C	0.994

dbSNP variants (sampled 300 via entrez): RS1000121497 (4:68070711 T>C,G), RS1000124008 (4:68063348 C>A,T), RS1000124088 (4:68101275 T>C), RS1000148256 (4:68111076 C>A,T), RS1000192090 (4:68092883 C>A,T), RS1000201841 (4:68104650 T>A), RS1000212526 (4:68109479 T>C), RS1000245126 (4:68064341 T>C,G), RS1000254124 (4:68104832 C>G), RS10003334 (4:68115994 C>T), RS1000402854 (4:68093182 C>G), RS10004522 (4:68068588 G>A,T), RS10004940 (4:68091190 C>T), RS1000499220 (4:68110676 G>A,T), RS1000514701 (4:68060052 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

2 associations (top):

Study	Trait	p-value
GCST003123_13	Severe influenza A (H1N1) infection	3.000000e-09
GCST004068_59	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ethyl-p-hydroxybenzoate	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
abrine	increases expression	1
Benzo(a)pyrene	increases methylation, decreases methylation	1
Lipopolysaccharides	increases expression, affects cotreatment, affects response to substance	1
Cyclosporine	increases methylation	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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