TMPRSS12

Summary

TMPRSS12 (transmembrane serine protease 12, HGNC:28779) is a protein-coding gene on chromosome 12q13.12, encoding Transmembrane protease serine 12 (Q86WS5). Required for male fertility.

Predicted to enable serine-type endopeptidase activity. Predicted to be involved in acrosome assembly and positive regulation of sperm capacitation. Predicted to act upstream of or within binding activity of sperm to zona pellucida and protein processing. Predicted to be located in acrosomal vesicle.

Source: NCBI Gene 283471 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_182559

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28779
Approved symbol	TMPRSS12
Name	transmembrane serine protease 12
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	MGC57341, CT151
Ensembl gene	ENSG00000186452
Ensembl biotype	protein_coding
Entrez	283471

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000398458, ENST00000551456

RefSeq mRNA: 1 — MANE Select: NM_182559 NM_182559

CCDS: CCDS44881

Canonical transcript exons

ENST00000398458 — 5 exons

Exon	Start	End
ENSE00001337221	50885246	50885388
ENSE00001337223	50858785	50859053
ENSE00001337227	50887262	50887884
ENSE00001644560	50843842	50844037
ENSE00002338286	50842926	50843151

Expression profiles

Bgee: expression breadth broad, 37 present calls, max score 86.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1104 / max 114.5756, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125458	0.1104	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	86.78	gold quality
left testis	UBERON:0004533	83.67	gold quality
right testis	UBERON:0004534	82.41	gold quality
testis	UBERON:0000473	81.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.99	gold quality
adult organism	UBERON:0007023	72.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	44.51	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	43.40	gold quality
ventricular zone	UBERON:0003053	43.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
oocyte	CL:0000023	43.26	gold quality
cortical plate	UBERON:0005343	43.23	gold quality
right adrenal gland cortex	UBERON:0035827	43.07	gold quality
islet of Langerhans	UBERON:0000006	42.89	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
skeletal muscle tissue	UBERON:0001134	42.16	gold quality
nasal cavity mucosa	UBERON:0001826	41.97	silver quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
muscle tissue	UBERON:0002385	41.04	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
metanephros cortex	UBERON:0010533	40.98	gold quality
metanephros	UBERON:0000081	40.69	silver quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting TMPRSS12, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-496	98.66	69.80	931
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-6773-3P	98.17	65.51	1213

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmprss12	ENSMUSG00000045631
rattus_norvegicus	Tmprss12	ENSRNOG00000031099

Paralogs (14): PRSS33 (ENSG00000103355), PLAT (ENSG00000104368), PLG (ENSG00000122194), PLGLB2 (ENSG00000125551), PRSS37 (ENSG00000165076), PRSS27 (ENSG00000172382), KLK15 (ENSG00000174562), PLGLB1 (ENSG00000183281), PRSS57 (ENSG00000185198), OVCH1 (ENSG00000187950), PRSS48 (ENSG00000189099), GZMM (ENSG00000197540), KLK9 (ENSG00000213022), PRSS50 (ENSG00000283706)

Protein

Protein identifiers

Transmembrane protease serine 12 — Q86WS5 (reviewed: Q86WS5)

All UniProt accessions (2): Q86WS5, F8WBX2

UniProt curated annotations — full annotation on UniProt →

Function. Required for male fertility. Plays a critical role in sperm capacitation and acrosome reactions during fertilization, and also plays a role in the regulation of proteins involved in spermatogenesis. Regulates protein pathways that promote chromosomal synapsis formation, double-strand break repair, formation of the inner mitochondrial membrane cristae and apoptosis in developing sperm. Required for normal sperm motility and binding to the zona pellucida, potentially via a role in ADAM3 protein maturation.

Subcellular location. Cell membrane. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. In testis, expressed in spermatocytes and spermatids (at protein level).

Miscellaneous. Expressed in colorectal cancer (at protein level).

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_872365* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

UniProt features (25 total): sequence variant 9, disulfide bond 4, active site 3, glycosylation site 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WS5-F1	81.14	0.57

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): 122 (charge relay system); 171 (charge relay system); 268 (charge relay system)

Disulfide bonds (4): 107–123, 206–274, 237–253, 264–294

Glycosylation sites (2): 219, 249

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_SINGLE_FERTILIZATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_CELL_MATURATION, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_PROTEIN_MATURATION, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_CELL_MATURATION, GOBP_SPERM_EGG_RECOGNITION

GO Biological Process (8): acrosome assembly (GO:0001675), spermatogenesis (GO:0007283), binding of sperm to zona pellucida (GO:0007339), protein processing (GO:0016485), positive regulation of sperm capacitation (GO:1902492), proteolysis (GO:0006508), single fertilization (GO:0007338), cell differentiation (GO:0030154)

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): acrosomal vesicle (GO:0001669), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
spermatid development	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
male gamete generation	1
sperm-egg recognition	1
proteolysis	1
protein maturation	1
sperm capacitation	1
positive regulation of multicellular organismal process	1
regulation of sperm capacitation	1
positive regulation of cell maturation	1
positive regulation of reproductive process	1
protein metabolic process	1
fertilization	1
cellular developmental 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
secretory granule	1
membrane	1
cell periphery	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS12	RNF215	Q9Y6U7	666
TMPRSS12	ERGIC2	Q96RQ1	571
TMPRSS12	ZNF10	P21506	544
TMPRSS12	TPPP2	P59282	507
TMPRSS12	FAM217A	Q8IXS0	478
TMPRSS12	SPATA31D4	Q6ZUB0	473
TMPRSS12	FAM170B	A6NMN3	438
TMPRSS12	OR6M1	Q8NGM8	436
TMPRSS12	HEMGN	Q9BXL5	433
TMPRSS12	SSMEM1	Q8WWF3	431
TMPRSS12	OR8H3	Q8N146	417
TMPRSS12	RSPH10B2	B2RC85	399
TMPRSS12	XAGE3	Q8WTP9	394
TMPRSS12	SPANXN5	Q5MJ07	391
TMPRSS12	TMPRSS11B	Q86T26	390

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TMPRSS12	FZD6	psi-mi:“MI:0914”(association)	0.530
TMPRSS12	SOAT1	psi-mi:“MI:0914”(association)	0.530
TMPRSS12	NPC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): BRCA1 (Two-hybrid), PIGB (Affinity Capture-MS), SNCA (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), PKD2 (Affinity Capture-MS), DPY19L4 (Affinity Capture-MS), SIDT2 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), FZD6 (Affinity Capture-MS), ZMPSTE24 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), SLC47A1 (Affinity Capture-MS), POMT1 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), FZD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVH4, A1L453, A4D1T9, A6H6T1, A8MTI9, A8QL53, A8QL57, B5U6Y3, E5RG02, O35453, O70169, P00745, P04070, P08709, P0CG03, P0DJE9, P22891, Q14BX2, Q28278, Q28661, Q2F9P2, Q2F9P4, Q2TV78, Q3V0Q7, Q402U7, Q4R7Y7, Q5FBW1, Q5M8S2, Q6AXZ6, Q6AY28, Q6IE62, Q6IE63, Q6PEW0, Q6UWB4, Q76HL1, Q7M756, Q7M761, Q7RTY5, Q7RTY7, Q7Z5A4

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	51
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

845 predictions. Top by Δscore:

Variant	Effect	Δscore
12:50843129:G:GT	donor_gain	1.0000
12:50843094:GC:G	donor_gain	0.9900
12:50843100:G:GT	donor_gain	0.9900
12:50843130:G:T	donor_gain	0.9900
12:50843133:G:GT	donor_gain	0.9900
12:50843134:G:T	donor_gain	0.9900
12:50843138:G:T	donor_gain	0.9900
12:50843152:G:T	donor_gain	0.9900
12:50843179:G:GT	donor_gain	0.9900
12:50843179:G:T	donor_gain	0.9900
12:50858783:A:AG	acceptor_gain	0.9900
12:50858783:AGC:A	acceptor_gain	0.9900
12:50858784:G:GG	acceptor_gain	0.9900
12:50858784:GC:G	acceptor_gain	0.9900
12:50858784:GCG:G	acceptor_gain	0.9900
12:50885387:GG:G	donor_gain	0.9900
12:50885388:GG:G	donor_gain	0.9900
12:50843044:G:GT	donor_gain	0.9800
12:50843099:GGCC:G	donor_gain	0.9800
12:50843152:G:GT	donor_gain	0.9800
12:50858855:A:G	donor_gain	0.9800
12:50843005:G:T	donor_gain	0.9700
12:50843049:C:T	donor_gain	0.9700
12:50843080:C:T	donor_gain	0.9700
12:50843111:G:GT	donor_gain	0.9700
12:50843134:G:GT	donor_gain	0.9700
12:50843150:GGGCA:G	donor_gain	0.9700
12:50843151:GGCAG:G	donor_gain	0.9700
12:50843841:GATT:G	acceptor_gain	0.9700
12:50843930:G:GA	donor_gain	0.9700

AlphaMissense

2269 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:50859034:G:C	W211C	0.995
12:50859034:G:T	W211C	0.995
12:50885350:T:A	C253S	0.994
12:50885351:G:C	C253S	0.994
12:50844023:C:G	C123W	0.992
12:50858918:G:C	A173P	0.992
12:50885302:T:A	C237S	0.992
12:50885303:G:C	C237S	0.992
12:50843925:T:A	W91R	0.991
12:50843925:T:C	W91R	0.991
12:50859017:T:C	C206R	0.991
12:50887271:G:T	G269W	0.991
12:50844022:G:A	C123Y	0.990
12:50859032:T:A	W211R	0.990
12:50859032:T:C	W211R	0.990
12:50885351:G:A	C253Y	0.990
12:50885384:G:A	C264Y	0.990
12:50887322:G:A	G286R	0.990
12:50887322:G:C	G286R	0.990
12:50887331:A:C	S289R	0.990
12:50887333:T:A	S289R	0.990
12:50887333:T:G	S289R	0.990
12:50843927:G:C	W91C	0.989
12:50843927:G:T	W91C	0.989
12:50843934:A:C	S94R	0.989
12:50843936:C:A	S94R	0.989
12:50843936:C:G	S94R	0.989
12:50859017:T:A	C206S	0.989
12:50859018:G:C	C206S	0.989
12:50859019:T:G	C206W	0.989

dbSNP variants (sampled 300 via entrez): RS1000120927 (12:50871486 T>C), RS1000275469 (12:50865566 T>G), RS1000327831 (12:50851319 T>C), RS1000356291 (12:50881698 C>T), RS1000417537 (12:50874809 T>TA), RS1000443929 (12:50851025 A>C), RS1000476840 (12:50859188 A>G,T), RS1000489207 (12:50873095 C>A,T), RS1000509737 (12:50860438 G>A), RS1000609346 (12:50867344 G>T), RS1000700802 (12:50876283 A>C), RS1000777256 (12:50852993 A>G), RS1000945938 (12:50847908 T>A), RS1001109991 (12:50886880 C>T), RS1001172399 (12:50847795 G>A)

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

1 associations (top):

Study	Trait	p-value
GCST90011898_16	Alanine aminotransferase levels	1.000000e-10

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
(+)-JQ1 compound	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1

Clinical trials (associated diseases)

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