TMPRSS9

Summary

TMPRSS9 (transmembrane serine protease 9, HGNC:30079) is a protein-coding gene on chromosome 19p13.3, encoding Transmembrane protease serine 9 (Q7Z410). Serase-1 and serase-2 are serine proteases that hydrolyze the peptides N-t-Boc-Gln-Ala-Arg-AMC and N-t-Boc-Gln-Gly-Arg-AMC.

The protein encoded by this gene is a membrane-bound type II serine polyprotease that is cleaved to release three different proteases. Two of the proteases are active and can be inhibited by serine protease inhibitors, and one is thought to be catalytically inactive. This gene enhances the invasive capability of pancreatic cancer cells and may be involved in cancer progression.

Source: NCBI Gene 360200 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 282 total — 2 likely-pathogenic
• GTEx eGene: eQTL in 35 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.33 (unconstrained)
• MANE Select transcript: NM_001395513
• Notable: 282 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30079
Approved symbol	TMPRSS9
Name	transmembrane serine protease 9
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178297
Ensembl biotype	protein_coding
OMIM	610477
Entrez	360200

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000696167

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

ENST00000696167, ENST00000395264, ENST00000587863, ENST00000592650, ENST00000648592, ENST00000649857, ENST00001141936

RefSeq mRNA: 3 — MANE Select: NM_001395513 NM_001385642, NM_001395513, NM_182973

CCDS: CCDS12088, CCDS92484

Canonical transcript exons

ENST00000696167 — 19 exons

Exon	Start	End
ENSE00001274976	2413700	2414018
ENSE00001296744	2415670	2415841
ENSE00001300593	2416538	2416809
ENSE00001305980	2418002	2418138
ENSE00001306827	2424089	2424257
ENSE00001359082	2421854	2422247
ENSE00001668204	2425357	2425493
ENSE00001768525	2425002	2425267
ENSE00003470409	2405374	2405545
ENSE00003568396	2408356	2408630
ENSE00003595010	2410258	2410394
ENSE00003639974	2401975	2402016
ENSE00003677737	2396539	2396666
ENSE00003687399	2403082	2403195
ENSE00003840185	2389761	2389927
ENSE00003966268	2398795	2398862
ENSE00003966269	2360265	2360360
ENSE00003966270	2399018	2399193
ENSE00004799910	2425927	2426261

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 73.43.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1592 / max 30.8571, expressed in 58 samples.

Highest expression (Bgee): lobe of liver, liver, testis, spleen, sural nerve.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TMPRSS9 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 35 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 37 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	2.2e-72	+1.20	19:2414338:C:G
Skin Sun Exposed Lower leg	eqtl	1.8e-33	+0.45	19:2426830:G:C
Cells Cultured fibroblasts	eqtl	1.3e-29	+0.44	19:2426830:G:C
Skin Not Sun Exposed Suprapubic	eqtl	5.8e-23	+0.42	19:2426830:G:C
Esophagus Mucosa	eqtl	4.8e-22	+0.49	19:2426830:G:C
Liver	eqtl	1.5e-17	-0.54	19:2395962:T:C
Nerve Tibial	eqtl	7.7e-14	+0.84	19:2411772:G:A
Adipose Subcutaneous	eqtl	8.7e-12	+0.33	19:2413963:G:C
Thyroid	eqtl	1.5e-11	+0.35	19:2420168:C:CAAA
Testis	eqtl	4.3e-07	-0.37	19:2423279:A:G
Artery Aorta	eqtl	1.9e-06	+0.27	19:2423279:A:G
Brain Cerebellum	eqtl	2.6e-06	+0.50	19:2360808:G:A
Adipose Visceral Omentum	eqtl	3.7e-06	+0.30	19:2426830:G:C
Esophagus Muscularis	eqtl	8.9e-06	+0.26	19:2438121:C:T
Cells EBV-transformed lymphocytes	eqtl	1.7e-05	-0.35	19:2393746:A:T
Muscle Skeletal	eqtl	1.7e-05	+0.48	19:2414689:A:T
Colon Sigmoid	eqtl	2.1e-05	+0.32	19:2360969:A:C
Esophagus Gastroesophageal Junction	eqtl	2.2e-05	+0.29	19:2430234:T:C
Pituitary	eqtl	2.4e-05	+0.44	19:2419548:A:G
Heart Left Ventricle	eqtl	3.1e-05	+0.37	19:2430234:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
173091	0.1405	54
173092	0.0187	12

Top tissues by expression

showing 100 of 132 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	73.43	gold quality
liver	UBERON:0002107	70.92	gold quality
right testis	UBERON:0004534	70.82	gold quality
left testis	UBERON:0004533	70.67	gold quality
testis	UBERON:0000473	69.69	gold quality
spleen	UBERON:0002106	67.73	gold quality
sural nerve	UBERON:0015488	64.70	gold quality
blood	UBERON:0000178	64.48	gold quality
bone marrow cell	CL:0002092	63.62	gold quality
bone marrow	UBERON:0002371	62.80	gold quality
ventricular zone	UBERON:0003053	62.09	gold quality
colonic epithelium	UBERON:0000397	61.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	61.24	gold quality
right coronary artery	UBERON:0001625	61.00	gold quality
stromal cell of endometrium	CL:0002255	60.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	60.24	gold quality
lower esophagus	UBERON:0013473	60.17	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	59.43	gold quality
popliteal artery	UBERON:0002250	59.10	gold quality
tibial artery	UBERON:0007610	59.08	gold quality
right adrenal gland	UBERON:0001233	58.93	gold quality
right adrenal gland cortex	UBERON:0035827	58.62	gold quality
body of pancreas	UBERON:0001150	58.39	gold quality
left adrenal gland	UBERON:0001234	58.19	gold quality
skeletal muscle tissue	UBERON:0001134	58.13	gold quality
ascending aorta	UBERON:0001496	57.76	gold quality
thoracic aorta	UBERON:0001515	57.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	57.60	gold quality
colon	UBERON:0001155	57.53	gold quality
mucosa of stomach	UBERON:0001199	57.43	gold quality
myometrium	UBERON:0001296	57.06	gold quality
left adrenal gland cortex	UBERON:0035825	56.94	gold quality
adrenal gland	UBERON:0002369	56.93	gold quality
descending thoracic aorta	UBERON:0002345	56.86	gold quality
skin of leg	UBERON:0001511	56.73	gold quality
left coronary artery	UBERON:0001626	56.58	gold quality
zone of skin	UBERON:0000014	56.31	gold quality
transverse colon	UBERON:0001157	56.31	gold quality
left uterine tube	UBERON:0001303	55.98	gold quality
fundus of stomach	UBERON:0001160	55.91	gold quality
esophagus	UBERON:0001043	55.85	gold quality
monocyte	CL:0000576	55.81	gold quality
intestine	UBERON:0000160	55.75	gold quality
skin of abdomen	UBERON:0001416	55.61	gold quality
body of uterus	UBERON:0009853	55.33	gold quality
cortex of kidney	UBERON:0001225	54.94	gold quality
leukocyte	CL:0000738	54.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	54.60	gold quality
muscle tissue	UBERON:0002385	54.56	gold quality
uterine cervix	UBERON:0000002	54.47	gold quality
apex of heart	UBERON:0002098	54.18	gold quality
multicellular organism	UBERON:0000468	54.12	gold quality
primary visual cortex	UBERON:0002436	54.10	gold quality
right ovary	UBERON:0002118	54.07	gold quality
left ovary	UBERON:0002119	54.04	gold quality
ovary	UBERON:0000992	53.81	gold quality
granulocyte	CL:0000094	53.65	gold quality
ectocervix	UBERON:0012249	53.25	gold quality
prostate gland	UBERON:0002367	53.14	gold quality
thoracic mammary gland	UBERON:0005200	52.97	gold quality
small intestine	UBERON:0002108	52.63	gold quality
endocervix	UBERON:0000458	52.60	gold quality
muscle of leg	UBERON:0001383	52.38	gold quality
urinary bladder	UBERON:0001255	52.30	gold quality
small intestine Peyer’s patch	UBERON:0003454	52.27	gold quality
temporal lobe	UBERON:0001871	52.17	gold quality
amygdala	UBERON:0001876	52.05	gold quality
prefrontal cortex	UBERON:0000451	52.03	gold quality
esophagus mucosa	UBERON:0002469	51.80	gold quality
vagina	UBERON:0000996	51.68	gold quality
heart left ventricle	UBERON:0002084	51.49	gold quality
right uterine tube	UBERON:0001302	51.46	gold quality
gastrocnemius	UBERON:0001388	51.37	gold quality
placenta	UBERON:0001987	51.29	gold quality
subcutaneous adipose tissue	UBERON:0002190	51.22	gold quality
heart	UBERON:0000948	51.13	gold quality
right atrium auricular region	UBERON:0006631	51.12	gold quality
adrenal tissue	UBERON:0018303	50.92	gold quality
minor salivary gland	UBERON:0001830	50.90	gold quality
right lobe of thyroid gland	UBERON:0001119	50.87	gold quality
saliva-secreting gland	UBERON:0001044	50.83	gold quality
pituitary gland	UBERON:0000007	50.60	gold quality
calcaneal tendon	UBERON:0003701	50.47	silver quality
frontal cortex	UBERON:0001870	50.14	gold quality
pancreas	UBERON:0001264	50.09	gold quality
tonsil	UBERON:0002372	49.82	gold quality
adenohypophysis	UBERON:0002196	49.70	gold quality
adipose tissue	UBERON:0001013	49.65	gold quality
tibial nerve	UBERON:0001323	49.64	gold quality
body of stomach	UBERON:0001161	49.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	49.36	gold quality
stomach	UBERON:0000945	49.30	gold quality
thyroid gland	UBERON:0002046	49.30	gold quality
putamen	UBERON:0001874	49.12	gold quality
cerebellum	UBERON:0002037	49.03	gold quality
left lobe of thyroid gland	UBERON:0001120	48.90	gold quality
cerebellar cortex	UBERON:0002129	48.78	gold quality
endometrium	UBERON:0001295	48.67	gold quality
cerebellar hemisphere	UBERON:0002245	48.62	gold quality
cerebral cortex	UBERON:0000956	48.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.36

HPA expression

RNA tissue specificity: Group enriched

57 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Corpus callosum	tissue	3.0
Postcentral gyrus	tissue	3.0
Hippocampus	tissue	2.8
Nucleus accumbens	tissue	2.6
Locus coeruleus	tissue	2.4
Cerebral cortex	tissue	1.6
Insular cortex	tissue	1.6
Amygdala	tissue	1.5
Choroid plexus	tissue	1.5
Medulla oblongata	tissue	1.5
Substantia nigra	tissue	1.5
Spleen	tissue	1.5
Ventral forebrain	tissue	1.5
Putamen	tissue	1.4
Spinal cord	tissue	1.4
Hippocampal formation	tissue	1.4
Periaqueductal gray	tissue	1.4
Somatosensory cortex	tissue	1.4
Retrosplenial cortex	tissue	1.4
Prefrontal cortex	tissue	1.3
Motor cortex	tissue	1.3
Basal ganglia	tissue	1.3
Midbrain	tissue	1.3
Thalamus	tissue	1.3
Hypothalamus	tissue	1.3
Cerebellum	tissue	1.3
Liver	tissue	1.3
Entorhinal cortex	tissue	1.3
Olfactory bulb	tissue	1.3
Septum	tissue	1.3
Occipital cortex	tissue	1.3
Superior colliculi	tissue	1.2
Retrosplenial and cingulate cortex	tissue	1.2
Pons	tissue	1.1
Temporal cortex	tissue	1.1
Testis	tissue	0.9
Bone marrow	tissue	0.7
Skin 1	tissue	0.5
Skeletal muscle	tissue	0.5
Caudate putamen	tissue	0.5
Breast	tissue	0.4
Pancreas	tissue	0.2
Thymus	tissue	0.2
Pituitary gland	tissue	0.1
Lymph node	tissue	0.1
Retina	tissue	0.1
Ovary	tissue	0.1
Vagina	tissue	0.1
Adipose tissue	tissue	0.1
Salivary gland	tissue	0.1
Endometrium 1	tissue	0.1
Small intestine	tissue	0.1
Gallbladder	tissue	0.1
Duodenum	tissue	0.1
Prostate	tissue	0.1
Adrenal gland	tissue	0.1
Appendix	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Lateral amygdala (5.5), Precentral gyrus (5.0), Flocculonodular lobe (4.0), Pontine raphe nucleus (4.0), Reticulotegmental nucleus (4.0).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 2.02e-43, LOEUF 1.33, missense Z -3.57 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000648592 — one region, missense o/e 1.19.

Literature-anchored findings (GeneRIF, showing 5)

• Polyserase-I is a human polyprotease with the ability to generate independent serine protease domains from a single translation product (PMID:12886014)
• The isolation and characterization of serase-1B, a splice variant of polyserase-1, is reported (accession AB109390.1). (PMID:16872279)
• SNP rs4806846 in TMPRSS9 gene is associated with neuroticism in a European sample. (PMID:23229837)
• These effects were mediated by the efficient conversion of pro-uPA to active uPA and high phosphorylation levels of ERK detected in the PANC-1 cells expressing exogenous polyserase-1. (PMID:24756697)
• Combination of whole exome sequencing and animal modeling identifies TMPRSS9 as a candidate gene for autism spectrum disorder. (PMID:31943016)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmprss9	ENSDARG00000029841
mus_musculus	Tmprss9	ENSMUSG00000059406
rattus_norvegicus	Tmprss9	ENSRNOG00000032429
drosophila_melanogaster	Sb	FBGN0003319
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), TMPRSS2 (ENSG00000184012), TMPRSS11B (ENSG00000185873), TMPRSS6 (ENSG00000187045), TMPRSS11A (ENSG00000187054), TMPRSS11F (ENSG00000198092), PRSS41 (ENSG00000215148)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3612246) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased body weight	1
abnormal social investigation	1
abnormal object recognition memory	1
increased thermal nociceptive threshold	1
abnormal social recognition	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
Drosophila erecta	C0HKA5	100.0%	Diamond
Phytophthora sojae strain P6497	G5AE35	100.0%	Diamond
Pan troglodytes	Q2F9P2	98.7%	Diamond
Pan paniscus	Q2F9P4	98.7%	Diamond
Nomascus leucogenys	Q5G268	98.5%	Diamond
Trachypithecus phayrei	Q5G266	98.3%	Diamond
Macaca mulatta	Q5G267	98.3%	Diamond
Glossina austeni	Q4TTV7	98.2%	Diamond
Salmo salar	P35032	97.8%	Diamond
Tachypleus tridentatus	P28175	97.2%	Diamond
Carcinoscorpius rotundicauda	Q26422	97.2%	Diamond
Bos taurus	P00741	96.8%	Diamond
Pongo pygmaeus	Q5G269	96.7%	Diamond
Manduca sexta	P35045	96.1%	Diamond
Saguinus labiatus	Q5G265	95.5%	Diamond
Oxyuranus microlepidotus	Q58L95	95.1%	Diamond
Pseudonaja textilis	Q1L659	93.6%	Diamond
Tropidechis carinatus	Q4QXT9	93.6%	Diamond
Capra hircus	Q28315	92.7%	Diamond
Papio cynocephalus	P16227	92.6%	Diamond
Lucilia cuprina	P35043	91.5%	Diamond
Desmodus rotundus	P15638	89.9%	Diamond
Cryptophis nigrescens	B5G6G5	89.2%	Diamond
Canis lupus familiaris	P19540	88.5%	Diamond
Acropora millepora	B8V7S0	87.4%	Diamond
Sus scrofa	P00761	86.4%	Diamond
Demansia vestigiata	A6MFK7	85.8%	Diamond
Mesocricetus auratus	P15156	84.7%	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
MIR7108	ncRNA	102466806
TIMM13	protein-coding	26517
GADD45B	protein-coding	4616
LMNB2	protein-coding	84823
LINC01775	ncRNA	101928602
SPPL2B	protein-coding	56928
LSM7	protein-coding	51690
PEAK3	protein-coding	374872
LINGO3	protein-coding	645191

Protein

Protein identifiers

Transmembrane protease serine 9 — Q7Z410 (reviewed: Q7Z410)

Alternative names: Polyserase-I, Polyserine protease 1

All UniProt accessions (2): A0A3B3IU58, Q7Z410

UniProt curated annotations — full annotation on UniProt →

Function. Serase-1 and serase-2 are serine proteases that hydrolyze the peptides N-t-Boc-Gln-Ala-Arg-AMC and N-t-Boc-Gln-Gly-Arg-AMC. In contrast, N-t-Boc-Ala-Phe-Lys-AMC and N-t-Boc-Ala-Pro-Ala-AMC are not significantly hydrolyzed.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in fetal human tissues, such as kidney, liver, lung and brain, and in a variety of tumor cell lines. Weakly expressed in adult tissues including skeletal muscle, liver, placenta and heart.

Post-translational modifications. Proteolytically cleaved to generate 3 independent serine protease chains. The cleaved chains may remain attached to the membrane thanks to disulfide bonds. It is unclear whether cleavage always takes place.

Activity regulation. Inhibited by serine protease inhibitors PMSF and 4-(2-aminoethyl)benzenesulfonyl fluoride, but not by EDTA.

Domain organisation. The serine protease 1 and 2 domains are catalytically active, whereas the serine protease 3 domain lacks the essential Ser residue of the catalytic triad at position 1009 and is predicted to be inactive.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (3): NP_001372571, NP_001382442, NP_892018 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR017324	Tmprss9	Family
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR043504

Pfam: PF00057, PF00089

UniProt features (51 total): disulfide bond 15, sequence variant 7, active site 6, chain 4, domain 4, glycosylation site 4, site 3, region of interest 2, topological domain 2, sequence conflict 2, compositionally biased region 1, transmembrane region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z410-F1	74.96	0.36

Human Protein Atlas

Protein class: Enzymes, Peptidases, Serine-type peptidases, Predicted membrane proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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 (9)

Position	Role
243	charge relay system
292	charge relay system
387	charge relay system
544	charge relay system
592	charge relay system
687	charge relay system
202–203	cleavage
503–504	cleavage
826–827	cleavage

Disulfide bonds (15)

Type	Positions
Disulfide bond	154–166, 161–180, 174–189, 228–244, 326–393, 358–372, 383–412, 529–545, 626–693, 658–672, 683–712, 853–869, 949–1015, 980–994, 1005–1034

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	547, 638, 663, 786

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: 22 (showing top): BRUECKNER_TARGETS_OF_MIRLET7A3_DN, GOBP_PROTEIN_MATURATION, GOBP_ZYMOGEN_ACTIVATION, GOBP_PROTEOLYSIS, chr19p13, GOMF_PEPTIDASE_ACTIVITY, GOBP_PROTEIN_PROCESSING, GOBP_PLASMINOGEN_ACTIVATION, GSE14386_UNTREATED_VS_IFNA_TREATED_ACT_PBMC_MS_PATIENT_UP, SNRNP70_TARGET_GENES, ZNF436_TARGET_GENES, BLANCO_MELO_MERS_COV_INFECTION_MCR5_CELLS_UP, SAFB2_TARGET_GENES, HAY_BONE_MARROW_ERYTHROBLAST, DESCARTES_FETAL_CEREBELLUM_OLIGODENDROCYTES

GO Biological Process (2): plasminogen activation (GO:0031639), 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 (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

13 GO namespaces:

Category	Terms
zymogen activation	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
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 15 of 338 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS9	TIMM13	P62206	758
TMPRSS9	CCDC120	Q96HB5	493
TMPRSS9	ASB12	Q8WXK4	475
TMPRSS9	LDLR	P01130	423
TMPRSS9	ZSCAN10	Q96SZ4	386
TMPRSS9	TMEM229B	Q8NBD8	369
TMPRSS9	LRRTM2	O43300	360
TMPRSS9	ERICH4	A6NGS2	348
TMPRSS9	PRSS36	Q5K4E3	332
TMPRSS9	CPD	O75976	329
TMPRSS9	DUOXA1	Q1HG43	327
TMPRSS9	PARP4	Q9UKK3	323
TMPRSS9	TMPRSS6	Q8IU80	314
TMPRSS9	ST14	Q9Y5Y6	312
TMPRSS9	DCANP1	Q8TF63	303

IntAct

BioGRID (4 interactions; top human partners by supporting records): CUL3 (Affinity Capture-MS), EEA1 (Cross-Linking-MS (XL-MS)), HNRNPH1 (Affinity Capture-RNA), NUDT21 (Affinity Capture-RNA)

Disease & clinical

Genetic variants

Variant evidence for TMPRSS9: 282 ClinVar records (2 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	225
Likely benign	32
Benign	4

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1321299	NM_001395513.1(TMPRSS9):c.1196C>A (p.Ser399Ter)	Likely pathogenic	criteria provided, single submitter	1
4293193	NM_001395513.1(TMPRSS9):c.950del (p.Leu317fs)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore TMPRSS9’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 2,030):

Position(s)	Effect	Δscore	Sites
19:2381457	acceptor_gain	1.0000
19:2389747	acceptor_gain	1.0000
19:2389752	acceptor_gain	1.0000
19:2399194–2399195	donor_loss	1.0000	5
19:2402017–2402018	donor_loss	1.0000	4
19:2405542	donor_gain	1.0000
19:2408354–2408355	acceptor_loss	1.0000	4
19:2410249–2410252	acceptor_gain	1.0000	3
19:2410395–2410396	donor_loss	1.0000	5
19:2416810–2416811	donor_loss	1.0000	5

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Skin Cutaneous Melanoma)

Disease associations

OMIM: gene MIM:610477 | disease phenotypes:

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
complex neurodevelopmental disorder	Limited	Autosomal recessive
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (2): complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

GWAS associations

3 associations:

Study	Trait	p-value
GCST012442_7	Age-related hearing impairment	4e-9
GCST004780_7	Cortisol levels (saliva)	3e-6
GCST001771_1	Neuroticism	8e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0005843	cortisol measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
trichostatin A	affects expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
quinocetone	increases expression	1
bisphenol S	decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Amiodarone	increases expression	1
Endosulfan	increases expression	1
Estradiol	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Thiram	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

showing 60 of 212 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	COMPLETED	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03577756	Not specified	COMPLETED	Neurodevelopmental Assessment of Infants With Cystic Fibrosis
NCT03654248	Not specified	COMPLETED	Let’s Get Organized in Adult Psychiatric/habilitation Care
NCT03659279	Not specified	COMPLETED	Let’s Get Organized Feasibility Study
NCT03722615	Not specified	COMPLETED	Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa
NCT03770832	Not specified	ACTIVE_NOT_RECRUITING	Wearable Sensors and Video Recordings to Monitor Motor Development
NCT03830879	Not specified	RECRUITING	Shenzhen Birth Cohort Study
NCT03835689	Not specified	COMPLETED	Strongest FamiliesTM Neurodevelopmental
NCT03882788	Not specified	COMPLETED	The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
NCT03922087	Not specified	COMPLETED	No-worry Baby Project
NCT03977259	Not specified	ACTIVE_NOT_RECRUITING	Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
NCT04043572	Not specified	UNKNOWN	The Biomarkers of Neurological Disease in Utero Study
NCT04096430	Not specified	RECRUITING	Evaluation of Effectiveness of Child-oriented Goal-setting in Paediatric Rehabilitation (the ENGAGE Approach)
NCT04108273	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children
NCT04201509	Not specified	COMPLETED	Validity of Neurocognitive Assessment Methods in Childhood ADHD