TMPRSS13

Summary

TMPRSS13 (transmembrane serine protease 13, HGNC:29808) is a protein-coding gene on chromosome 11q23.3, encoding Transmembrane protease serine 13 (Q9BYE2). Serine protease.

This gene encodes a member of the type II transmembrane serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Transmembrane serine proteases are regulated by protease inhibitors and known to function in development, homeostasis, infection, and tumorigenesis. This protein facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins.

Source: NCBI Gene 84000 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 93 total
• GTEx eGene: eQTL in 11 tissues, sQTL in 8 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.97 (unconstrained)
• MANE Select transcript: NM_001077263
• Notable: 93 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29808
Approved symbol	TMPRSS13
Name	transmembrane serine protease 13
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MSPL, MSPS
Ensembl gene	ENSG00000137747
Ensembl biotype	protein_coding
OMIM	610050
Entrez	84000

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000524993

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 2, TSL 3: 1

ENST00000524993, ENST00000430170, ENST00000445164, ENST00000525794, ENST00000526090, ENST00000528135, ENST00000528626, ENST00000966153, ENST00001017064, ENST00001017065, ENST00001143388

RefSeq mRNA: 4 — MANE Select: NM_001077263 NM_001077263, NM_001206789, NM_001206790, NM_001244995

CCDS: CCDS41721, CCDS55788, CCDS55789, CCDS58185

Canonical transcript exons

ENST00000524993 — 13 exons

Exon	Start	End
ENSE00000930746	117911768	117911860
ENSE00000930747	117910707	117910750
ENSE00000991437	117917170	117917274
ENSE00000991442	117905638	117905736
ENSE00001053164	117903959	117904101
ENSE00001209120	117903655	117903807
ENSE00002142359	117929287	117929402
ENSE00002179716	117900641	117902265
ENSE00003515382	117918409	117918838
ENSE00003570318	117914392	117914514
ENSE00003685985	117913777	117913906
ENSE00003988831	117908612	117908784
ENSE00003988841	117909806	117909968

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 91.73.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4986 / max 48.5061, expressed in 313 samples.

Highest expression (Bgee): upper arm skin, skin of leg, skin of abdomen, zone of skin, lower esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TMPRSS13 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 8 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	3.7e-132	+1.24	11:117903431:C:G
Skin Not Sun Exposed Suprapubic	sqtl	2.5e-107	+1.25	11:117903431:C:G
Esophagus Mucosa	sqtl	1.4e-87	+1.25	11:117903431:C:G
Esophagus Mucosa	eqtl	2.5e-78	-0.50	11:117929454:C:T
Skin Sun Exposed Lower leg	eqtl	4.4e-47	-0.18	11:117929368:T:C
Skin Not Sun Exposed Suprapubic	eqtl	5.2e-28	-0.19	11:117929368:T:C
Thyroid	sqtl	1.2e-17	+0.63	11:117903431:C:G
Lung	sqtl	2.9e-13	-0.58	11:117905180:C:A
Minor Salivary Gland	eqtl	8.4e-12	-0.47	11:117929208:T:C
Lung	eqtl	1.4e-06	+0.21	11:117812850:A:C
Minor Salivary Gland	sqtl	1.5e-05	+0.90	11:117903431:C:G
Whole Blood	eqtl	2.5e-03	+0.17	11:117993114:T:C
Thyroid	eqtl	6.4e-03	+0.14	11:117929208:T:C
Breast Mammary Tissue	sqtl	6.5e-03	-0.38	11:117897694:A:G
Pancreas	sqtl	8.6e-03	+1.84	11:117397773:T:C
Adipose Subcutaneous	eqtl	9.2e-03	+0.14	11:117993114:T:C
Adrenal Gland	eqtl	1.5e-02	+0.67	11:117878400:G:C
Colon Sigmoid	eqtl	1.6e-02	+0.22	11:117993114:T:C
Cells EBV-transformed lymphocytes	eqtl	3.8e-02	+0.26	11:117855759:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
122544	1.4986	313

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	91.73	gold quality
skin of leg	UBERON:0001511	89.86	gold quality
skin of abdomen	UBERON:0001416	87.93	gold quality
zone of skin	UBERON:0000014	87.39	gold quality
lower esophagus mucosa	UBERON:0035834	85.26	gold quality
esophagus mucosa	UBERON:0002469	82.61	gold quality
nasal cavity epithelium	UBERON:0005384	82.21	gold quality
gingival epithelium	UBERON:0001949	80.67	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	80.61	gold quality
minor salivary gland	UBERON:0001830	79.95	gold quality
saliva-secreting gland	UBERON:0001044	79.54	gold quality
heart right ventricle	UBERON:0002080	79.28	gold quality
mouth mucosa	UBERON:0003729	79.28	gold quality
cortical plate	UBERON:0005343	79.14	gold quality
sperm	CL:0000019	78.99	gold quality
gingiva	UBERON:0001828	78.60	gold quality
amniotic fluid	UBERON:0000173	77.83	gold quality
right lobe of thyroid gland	UBERON:0001119	77.64	gold quality
left lobe of thyroid gland	UBERON:0001120	76.53	gold quality
vena cava	UBERON:0004087	76.45	gold quality
cerebellar vermis	UBERON:0004720	76.37	gold quality
upper leg skin	UBERON:0004262	76.14	gold quality
endothelial cell	CL:0000115	76.13	gold quality
thyroid gland	UBERON:0002046	75.62	gold quality
vastus lateralis	UBERON:0001379	74.28	gold quality
superficial temporal artery	UBERON:0001614	74.27	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.02	gold quality
palpebral conjunctiva	UBERON:0001812	73.51	gold quality
buccal mucosa cell	CL:0002336	73.23	silver quality
quadriceps femoris	UBERON:0001377	72.65	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	71.91	gold quality
body of tongue	UBERON:0011876	71.79	gold quality
biceps brachii	UBERON:0001507	71.66	gold quality
tonsil	UBERON:0002372	71.31	gold quality
epithelial cell of pancreas	CL:0000083	71.29	gold quality
vagina	UBERON:0000996	71.29	gold quality
granulocyte	CL:0000094	71.27	gold quality
cardia of stomach	UBERON:0001162	71.21	gold quality
subthalamic nucleus	UBERON:0001906	71.21	gold quality
inferior vagus X ganglion	UBERON:0005363	71.17	gold quality
lateral globus pallidus	UBERON:0002476	70.87	gold quality
pons	UBERON:0000988	70.83	gold quality
dorsal plus ventral thalamus	UBERON:0001897	70.78	gold quality
lateral nuclear group of thalamus	UBERON:0002736	70.67	gold quality
ventral tegmental area	UBERON:0002691	70.64	gold quality
substantia nigra pars reticulata	UBERON:0001966	70.50	gold quality
pharyngeal mucosa	UBERON:0000355	70.40	gold quality
tongue	UBERON:0001723	70.32	gold quality
esophagus squamous epithelium	UBERON:0006920	70.11	gold quality
substantia nigra pars compacta	UBERON:0001965	70.10	gold quality
pericardium	UBERON:0002407	70.09	gold quality
nipple	UBERON:0002030	70.08	silver quality
saphenous vein	UBERON:0007318	69.82	gold quality
trachea	UBERON:0003126	69.81	gold quality
Brodmann (1909) area 46	UBERON:0006483	69.69	gold quality
pylorus	UBERON:0001166	69.58	gold quality
secondary oocyte	CL:0000655	69.52	gold quality
medulla oblongata	UBERON:0001896	69.50	gold quality
islet of Langerhans	UBERON:0000006	69.49	gold quality
placenta	UBERON:0001987	69.36	gold quality
superior surface of tongue	UBERON:0007371	69.35	gold quality
superior vestibular nucleus	UBERON:0007227	69.26	gold quality
globus pallidus	UBERON:0001875	69.01	gold quality
nasal cavity mucosa	UBERON:0001826	68.86	gold quality
right lung	UBERON:0002167	68.82	gold quality
renal medulla	UBERON:0000362	68.78	gold quality
epithelium of mammary gland	UBERON:0003244	68.27	silver quality
medial globus pallidus	UBERON:0002477	68.14	gold quality
mammary duct	UBERON:0001765	68.11	silver quality
penis	UBERON:0000989	68.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	67.97	gold quality
mammalian vulva	UBERON:0000997	67.96	silver quality
entorhinal cortex	UBERON:0002728	67.84	gold quality
Brodmann (1909) area 23	UBERON:0013554	67.58	gold quality
parietal lobe	UBERON:0001872	67.02	gold quality
pancreas	UBERON:0001264	66.94	gold quality
decidua	UBERON:0002450	66.88	gold quality
cartilage tissue	UBERON:0002418	66.84	gold quality
thymus	UBERON:0002370	66.72	silver quality
trigeminal ganglion	UBERON:0001675	66.63	gold quality
postcentral gyrus	UBERON:0002581	66.53	gold quality
upper lobe of left lung	UBERON:0008952	66.46	gold quality
trabecular bone tissue	UBERON:0002483	66.36	gold quality
middle temporal gyrus	UBERON:0002771	66.34	gold quality
leukocyte	CL:0000738	65.97	gold quality
dorsal root ganglion	UBERON:0000044	65.93	gold quality
monocyte	CL:0000576	65.83	gold quality
body of pancreas	UBERON:0001150	65.34	gold quality
synovial joint	UBERON:0002217	65.29	gold quality
upper lobe of lung	UBERON:0008948	65.02	gold quality
myocardium	UBERON:0002349	64.74	gold quality
oral cavity	UBERON:0000167	64.58	silver quality
lymph node	UBERON:0000029	64.27	gold quality
esophagus	UBERON:0001043	64.20	gold quality
oocyte	CL:0000023	64.08	gold quality
seminal vesicle	UBERON:0000998	64.04	gold quality
layer of synovial tissue	UBERON:0007616	63.98	gold quality
urethra	UBERON:0000057	63.58	gold quality
mammary gland	UBERON:0001911	63.52	gold quality
lung	UBERON:0002048	63.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	10.38
E-ANND-3	yes	5.42

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 69 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Skin 1	tissue	26.7
Vagina	tissue	8.5
Esophagus	tissue	7.7
Breast	tissue	6.6
Cervix	tissue	6.3
Thyroid gland	tissue	5.0
Tonsil	tissue	4.5
Salivary gland	tissue	4.0
Lung	tissue	3.6
Placenta	tissue	2.8
Hippocampus	tissue	2.5
Postcentral gyrus	tissue	2.2
Pancreas	tissue	1.7
Nucleus accumbens	tissue	1.7
Lymph node	tissue	1.2
Locus coeruleus	tissue	1.2
Choroid plexus	tissue	1.1
Spleen	tissue	1.1
Thymus	tissue	0.9
Cerebral cortex	tissue	0.8
Prostate	tissue	0.8
Somatosensory cortex	tissue	0.8
Appendix	tissue	0.7
Occipital cortex	tissue	0.7
Epididymis	tissue	0.6
Temporal cortex	tissue	0.6
Urinary bladder	tissue	0.5
Endometrium 1	tissue	0.5
Bone marrow	tissue	0.5
Testis	tissue	0.4
Rectum	tissue	0.4
Colon	tissue	0.4
Motor cortex	tissue	0.4
Small intestine	tissue	0.4
Hippocampal formation	tissue	0.4
Entorhinal cortex	tissue	0.4
Retrosplenial and cingulate cortex	tissue	0.4
Olfactory bulb	tissue	0.4
Prefrontal cortex	tissue	0.3
Basal ganglia	tissue	0.3
Putamen	tissue	0.3
Hypothalamus	tissue	0.3
Superior colliculi	tissue	0.3
Gallbladder	tissue	0.3
Kidney	tissue	0.3
Duodenum	tissue	0.3
Spinal cord	tissue	0.3
Ventral forebrain	tissue	0.3
Fallopian tube	tissue	0.3
Retrosplenial cortex	tissue	0.3
Insular cortex	tissue	0.3
Pituitary gland	tissue	0.2
Pons	tissue	0.2
Adipose tissue	tissue	0.2
Skeletal muscle	tissue	0.2
Smooth muscle	tissue	0.2
Amygdala	tissue	0.2
Midbrain	tissue	0.2
Medulla oblongata	tissue	0.2
Thalamus	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Hippocampus, CA3 (3.6), Posterior cingulate cortex (3.1), Hippocampus, CA1 (2.9), Dentate gyrus (2.7), Parietal operculum (2.5).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 3.2e-13, LOEUF 0.967, missense Z 1.61 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000524993 — one region, missense o/e 0.84.

Literature-anchored findings (GeneRIF, showing 11)

• cloning of MSPL/TMPRSS13, which may play roles in the proteolytic processing of prohormones, precursors of growth factors, and also play roles in the pathogenicity of many viruses and bacteria in vivo (PMID:17981585)
• The authors report that serine proteases, MSPL and its splice variant TMPRSS13, are novel candidates for proteases processing HA proteins of highly pathogenic avian influenza (HPAI) viruses. (PMID:20219906)
• results suggest that TMPRSS13 functions as an HGF-converting protease, the activity of which may be regulated by HAI-1 (PMID:20977675)
• 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)
• The data provide novel insight into the cellular properties of TMPRSS13 and highlight phosphorylation of TMPRSS13 as a novel post-translational modification of this TTSP family member and potentially other members of this family of proteases. (PMID:28710277)
• TMPRSS13 promotes cell survival, invasion, and resistance to drug-induced apoptosis in colorectal cancer. (PMID:32807808)
• The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy. (PMID:32868877)
• TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein. (PMID:33671076)
• Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza. (PMID:33820827)
• Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization. (PMID:34562451)
• IL4I1 binds to TMPRSS13 and competes with SARS-CoV-2 spike. (PMID:36131918)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmprss13b	ENSDARG00000077573
mus_musculus	Tmprss13	ENSMUSG00000037129
rattus_norvegicus	Tmprss13	ENSRNOG00000016397
drosophila_melanogaster	Sb	FBGN0003319
drosophila_melanogaster	CG17242	FBGN0250841

Paralogs (17): PRSS22 (ENSG00000005001), PRSS21 (ENSG00000007038), TMPRSS11E (ENSG00000087128), HPN (ENSG00000105707), 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2682935) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal epidermis stratum corneum morphology	1
short vibrissae	1
impaired skin barrier function	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Phytophthora sojae strain P6497	G5AE35	100.0%	Diamond
Phytophthora sojae	Q945T8	100.0%	Diamond
Pongo abelii	Q5R5E8	99.3%	Diamond
Pan troglodytes	Q5G271	99.2%	Diamond
Nomascus leucogenys	Q5G268	98.5%	Diamond
Gorilla gorilla gorilla	Q5G270	98.5%	Diamond
Trachypithecus phayrei	Q5G266	98.3%	Diamond
Macaca mulatta	Q5G267	98.3%	Diamond
Felis catus	Q9BH09	97.7%	Diamond
Pongo pygmaeus	Q5G269	96.7%	Diamond
Saguinus labiatus	Q5G265	95.5%	Diamond
Macaca fascicularis	O46644	94.2%	Diamond
Bos taurus	P06868	92.9%	Diamond
Capra hircus	Q28315	92.7%	Diamond
Papio cynocephalus	P16227	92.6%	Diamond
Desmodus rotundus	P15638	89.9%	Diamond
Canis lupus familiaris	Q867B0	89.9%	Diamond
Sus scrofa	P00772	89.5%	Diamond
Cryptophis nigrescens	B5G6G5	89.2%	Diamond
Acropora millepora	B8V7S0	87.4%	Diamond
Ovis aries	P81286	86.3%	Diamond
Pseudechis porphyriacus	Q58L93	86.1%	Diamond
Meriones unguiculatus	P50342	84.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
IL10RA	protein-coding	3587
TMPRSS4	protein-coding	56649
SCN4B	protein-coding	6330
FXYD6-AS1	ncRNA	123706543
CEP164	protein-coding	22897
FXYD2	protein-coding	486
FXYD6	protein-coding	53826
DSCAML1	protein-coding	57453
SMIM35	protein-coding	100526771
FXYD6-FXYD2	protein-coding	100533181

Protein

Protein identifiers

Transmembrane protease serine 13 — Q9BYE2 (reviewed: Q9BYE2)

Alternative names: Membrane-type mosaic serine protease

All UniProt accessions (2): Q9BYE2, E9PR79

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease. Cleaves the proform of PRSS8/prostasin to form the active protein. Cleaves the proform of HGF to form the active protein which promotes MAPK signaling. Promotes the formation of the stratum corneum and subsequently the epidermal barrier in embryos.

Subunit / interactions. Interacts with SPINT1/HAI-1; the interaction promotes the phosphorylation and cell membrane localization of TMPRSS13. Interacts with SPINT2/HAI-2; the interaction promotes the phosphorylation and cell membrane localization of TMPRSS13.

Subcellular location. Cell membrane. Secreted. Cytoplasm.

Tissue specificity. Expressed in placenta. Predominantly expressed in lung, placenta, pancreas, and prostate. Expressed in lung, placenta, pancreas, and prostate. Weakly expressed in testis and peripheral blood lymphocytes.

Post-translational modifications. The inactive zymogen is post-translationally modified and then trafficked to the cell surface, whereby it undergoes autocatalytic cleavage resulting in an activated form that is released extracellularly. Phosphorylation is required for localization at the cell surface. Phosphorylation increases following inhibition of protease activity by SPINT2/HAI-2. N-glycosylation of Asn-405 and Asn-445 is required for exit from the endoplasmic reticulum and trafficking to the cell surface. Also required for autocleavage of the zymogen, activation and secretion of the mature protein.

Activity regulation. Cleavage of HGF is inhibited by SPINT1/HAI-1 via the BPTI/Kunitz inhibitor 1 domain.

Polymorphism. The repeat A-S-P-A-[GLQR] is polymorphic and the number of copies varies between 12 to 14.

Similarity. Belongs to the peptidase S1 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9BYE2-1	1, MSPL	yes
Q9BYE2-2	2
Q9BYE2-3	3, MSPS
Q9BYE2-4	4
Q9BYE2-6	6

RefSeq proteins (4): NP_001070731, NP_001193718, NP_001193719, NP_001231924 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001190	SRCR	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR017327	Peptidase_S1A_TMPRSS13	Family
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR036772	SRCR-like_dom_sf	Homologous_superfamily
IPR043504

Pfam: PF00089, PF15494

Enzyme classification (BRENDA)

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

UniProt features (108 total): strand 26, repeat 16, mutagenesis site 10, helix 7, disulfide bond 6, splice variant 6, region of interest 5, compositionally biased region 5, sequence conflict 5, turn 4, glycosylation site 4, domain 3, active site 3, topological domain 2, site 2, sequence variant 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
6KD5	Crystal structure of the extracellular domain of MSPL/TMPRSS13 in complex with …	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYE2-F1	75.14	0.51

Human Protein Atlas

Protein class: Enzymes, Peptidases, Serine-type peptidases, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; plasma membrane

Antibody reliability (HPA): IF approved

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 (5)

Position	Role
366	charge relay system
414	charge relay system
511	charge relay system
228–229	cleavage; by autolysis; required for cell surface localization and secretion
325	required for autocleavage and prss8 cleavage

Disulfide bonds (6)

Type	Positions
Disulfide bond	250–314, 263–317, 351–367, 448–517, 480–496, 507–535

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	255, 292, 405, 445

Mutagenesis-validated functional residues (10)

Position	Phenotype
196	no effect on autocleavage.
201	no effect on autocleavage.
210	no effect on autocleavage.
228	significantly reduces autocleavage and cleavage of substrates. abolishes phosphorylation when inhibited by spint2/hai-2, also reduces …
255	no effect on autocleavage. no effect on prss8 cleavage and activation.
292	no effect on autocleavage. no effect on prss8 cleavage and activation.
325	abolishes autocleavage. abolishes prss8 cleavage and activation. increases localization to the cell surface. no effect on glycosylation.
405	loss of localization to the cell surface even in the presence of the inhibitor spint2. reduces prss8 cleavage and activation. no effect on …
445	reduces autocleavage. loss of localization to the cell surface even in the presence of the inhibitor spint2. reduces prss8 cleavage and …
511	abolishes autocleavage. abolishes serine protease activity including prss8 cleavage and activation. increases localization to the cell …

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 79 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_PROTEIN_MATURATION, GOCC_BLOOD_MICROPARTICLE, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, MIKKELSEN_MCV6_LCP_WITH_H3K27ME3, GOBP_PROTEIN_PROCESSING, LIM_MAMMARY_STEM_CELL_DN, GSE13522_WT_VS_IFNAR_KO_SKING_T_CRUZI_Y_STRAIN_INF_UP, GLI1_TARGET_GENES, GREB1_TARGET_GENES, ZNF768_TARGET_GENES, MIR8485, MIR4795_3P

GO Biological Process (2): protein processing (GO:0016485), proteolysis (GO:0006508)

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 (5): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020), blood microparticle (GO:0072562), extracellular region (GO:0005576)

GO top-level categories

16 GO namespaces:

Category	Terms
cellular anatomical structure	4
proteolysis	1
protein maturation	1
protein metabolic 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
intracellular anatomical structure	1
membrane	1
cell periphery	1
extracellular region	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
blood microparticle	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 550 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS13	ERV3-1	Q14264	656
TMPRSS13	ERVFRD-1	P60508	652
TMPRSS13	ERVW-1	Q9UQF0	568
TMPRSS13	FURIN	P09958	547
TMPRSS13	SPINT1	O43278	498
TMPRSS13	KRTAP4-5	Q9BYR2	492
TMPRSS13	ACE2	Q9BYF1	487
TMPRSS13	SPINT2	O43291	481
TMPRSS13	TEKT5	Q96M29	421
TMPRSS13	SLC46A2	Q9BY10	417
TMPRSS13	GOLGA8B	A8MQT2	390
TMPRSS13	CTSL	P07711	374
TMPRSS13	DEPDC4	Q8N2C3	371
TMPRSS13	PRSS36	Q5K4E3	370
TMPRSS13	ADAM8	P78325	364

IntAct

Human interaction partners of TMPRSS13 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
PROS1	association	0.350	1
TOR1A	association	0.350	1

BioGRID (107 interactions; top human partners by supporting records): IL4I1 (Co-localization; 4 records), ADAM10 (Affinity Capture-MS), ADAM9 (Affinity Capture-MS), ADAMTS1 (Affinity Capture-MS), ADPGK (Affinity Capture-MS), AIRE (Affinity Capture-MS), ALCAM (Affinity Capture-MS), ALG9 (Affinity Capture-MS), ARL2BP (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), B4GALT4 (Affinity Capture-MS), B4GALT5 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), C1GALT1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for TMPRSS13: 93 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	3
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 1,188):

Position(s)	Effect	Δscore	Sites
11:117904112	acceptor_gain	1.0000
11:117904117	acceptor_gain	1.0000
11:117911780	donor_gain	1.0000
11:117911861–117911862	acceptor_loss	1.0000	5
11:117911865	acceptor_gain	1.0000
11:117914390–117914391	donor_loss	1.0000	5
11:117929339	donor_gain	1.0000
11:117902266–117902267	acceptor_loss	0.9900	6
11:117903653–117903654	donor_loss	0.9900	5
11:117903808–117903809	acceptor_loss	0.9900	5

AlphaMissense

987 missense substitutions predicted likely pathogenic (of 3,664 scored), across 237 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M494	9	0.985	0.997
M558	9	0.757	0.878
D510	8	0.998	0.999
D414	8	0.997	1.000
D505	8	0.997	0.999
H366	8	0.994	0.998
S511	8	0.991	0.997
S530	8	0.991	0.999
H349	8	0.946	0.989
D222	8	0.928	0.973
D411	8	0.892	0.950
F368	8	0.889	0.983
F229	8	0.881	0.985
C367	7	0.999	1.000
C496	7	0.999	1.000
C507	7	0.999	1.000
C535	7	0.999	1.000
C351	7	0.998	0.999
C480	7	0.998	1.000
W531	7	0.998	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:610050 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, affects methylation	2
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	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
(+)-JQ1 compound	decreases expression	1
Acetaminophen	decreases expression	1
Vehicle Emissions	increases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Estradiol	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.