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 peptidase activity. Predicted to be involved in acrosome assembly; positive regulation of sperm capacitation; and protein processing. Predicted to act upstream of or within binding activity of sperm to zona pellucida. Predicted to be located in cytoplasmic vesicle and plasma membrane. Predicted to be active in acrosomal vesicle.

Source: NCBI Gene 283471 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 65 total
• GTEx eGene: eQTL in 2 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.49 (unconstrained)
• MANE Select transcript: NM_182559
• Notable: 65 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 3 — 3 protein_coding

MANE Select: ENST00000398458

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

ENST00000398458, ENST00000551456, ENST00001137983

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.

Highest expression (Bgee): sperm, testis, male germ line stem cell (sensu Vertebrata) in testis, adult organism, primordial germ cell in gonad.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TMPRSS12 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 2 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	5.6e-07	-0.14	12:50862282:A:G
Thyroid	eqtl	1.7e-02	-0.23	12:50829796:G:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
125458	0.1104	3

Top tissues by expression

showing 100 of 221 tissues 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
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
skin of hip	UBERON:0001554	40.23	silver quality
right adrenal gland	UBERON:0001233	40.22	silver quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
oviduct epithelium	UBERON:0004804	40.03	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
deltoid	UBERON:0001476	39.83	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
urethra	UBERON:0000057	39.80	gold quality
adrenal cortex	UBERON:0001235	39.80	silver quality
heart right ventricle	UBERON:0002080	39.79	gold quality
pericardium	UBERON:0002407	39.77	gold quality
layer of synovial tissue	UBERON:0007616	39.77	gold quality
placenta	UBERON:0001987	39.76	silver quality
endothelial cell	CL:0000115	39.75	gold quality
synovial joint	UBERON:0002217	39.70	gold quality
dorsal root ganglion	UBERON:0000044	39.68	gold quality
nipple	UBERON:0002030	39.68	gold quality
bronchial epithelial cell	CL:0002328	39.65	gold quality
decidua	UBERON:0002450	39.65	gold quality
penis	UBERON:0000989	39.64	gold quality
gingiva	UBERON:0001828	39.64	gold quality
bronchus	UBERON:0002185	39.64	gold quality
trigeminal ganglion	UBERON:0001675	39.63	gold quality
tendon of biceps brachii	UBERON:0008188	39.60	gold quality
inferior vagus X ganglion	UBERON:0005363	39.57	gold quality
superior surface of tongue	UBERON:0007371	39.56	gold quality
lower esophagus mucosa	UBERON:0035834	39.56	gold quality
pylorus	UBERON:0001166	39.55	gold quality
stromal cell of endometrium	CL:0002255	39.53	gold quality
renal medulla	UBERON:0000362	39.53	gold quality
left adrenal gland	UBERON:0001234	39.53	silver quality
pons	UBERON:0000988	39.51	gold quality
thymus	UBERON:0002370	39.50	gold quality
medulla oblongata	UBERON:0001896	39.48	gold quality
superior vestibular nucleus	UBERON:0007227	39.47	gold quality
cardia of stomach	UBERON:0001162	39.46	gold quality
colonic mucosa	UBERON:0000317	39.45	gold quality
parietal pleura	UBERON:0002400	39.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	39.40	gold quality
dorsal plus ventral thalamus	UBERON:0001897	39.38	gold quality
tongue	UBERON:0001723	39.37	gold quality
ganglionic eminence	UBERON:0004023	39.37	gold quality
cerebellar vermis	UBERON:0004720	39.37	gold quality
oral cavity	UBERON:0000167	39.35	gold quality
subthalamic nucleus	UBERON:0001906	39.35	gold quality
ventral tegmental area	UBERON:0002691	39.35	gold quality
kidney	UBERON:0002113	39.33	gold quality
trachea	UBERON:0003126	39.33	gold quality
parietal lobe	UBERON:0001872	39.32	gold quality
vena cava	UBERON:0004087	39.31	gold quality
pharyngeal mucosa	UBERON:0000355	39.27	gold quality
substantia nigra pars compacta	UBERON:0001965	39.23	gold quality
visceral pleura	UBERON:0002401	39.23	gold quality
postcentral gyrus	UBERON:0002581	39.23	gold quality
body of tongue	UBERON:0011876	39.22	gold quality
medial globus pallidus	UBERON:0002477	39.18	gold quality
trabecular bone tissue	UBERON:0002483	39.18	gold quality
globus pallidus	UBERON:0001875	39.15	gold quality
substantia nigra pars reticulata	UBERON:0001966	39.11	gold quality
entorhinal cortex	UBERON:0002728	39.05	gold quality
nasal cavity epithelium	UBERON:0005384	39.04	gold quality
lateral nuclear group of thalamus	UBERON:0002736	39.00	gold quality
corpus epididymis	UBERON:0004359	38.98	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

HPA expression

RNA tissue specificity: Tissue enriched

38 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Testis	tissue	20.2
Choroid plexus	tissue	1.8
Postcentral gyrus	tissue	1.5
Nucleus accumbens	tissue	1.1
Hippocampus	tissue	1.0
Locus coeruleus	tissue	0.9
Epididymis	tissue	0.4
Cerebral cortex	tissue	0.3
Basal ganglia	tissue	0.3
Putamen	tissue	0.3
Ventral forebrain	tissue	0.3
Retrosplenial and cingulate cortex	tissue	0.3
Septum	tissue	0.3
Occipital cortex	tissue	0.3
Insular cortex	tissue	0.3
Motor cortex	tissue	0.2
Amygdala	tissue	0.2
Midbrain	tissue	0.2
Hypothalamus	tissue	0.2
Cerebellum	tissue	0.2
Substantia nigra	tissue	0.2
Spinal cord	tissue	0.2
Hippocampal formation	tissue	0.2
Entorhinal cortex	tissue	0.2
Periaqueductal gray	tissue	0.2
Olfactory bulb	tissue	0.2
Somatosensory cortex	tissue	0.2
Retrosplenial cortex	tissue	0.2
Skin 1	tissue	0.1
Breast	tissue	0.1
Prefrontal cortex	tissue	0.1
Retina	tissue	0.1
Pons	tissue	0.1
Medulla oblongata	tissue	0.1
Thalamus	tissue	0.1
Superior colliculi	tissue	0.1
Corpus callosum	tissue	0.1
Temporal cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Vermis (2.0), Flocculonodular lobe (1.9), Cerebellar cortex (1.7), Angular gyrus (white matter) (1.5), Area striata (1.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting TMPRSS12 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 36 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1.04e-09, LOEUF 1.49, missense Z -0.213 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000398458 — one region, missense o/e 1.00.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1922252) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 23 distinct phenotype terms.

Mouse phenotype (MP)	Records
male infertility	3
asthenozoospermia	2
impaired fertilization	1
abnormal spermatogenesis	1
abnormal eye morphology	1
increased vertical activity	1
oligozoospermia	1
impaired sperm capacitation	1
impaired acrosome reaction	1
abnormal sperm physiology	1
decreased male germ cell number	1
abnormal male meiosis	1
decreased fertilization frequency	1
abnormal sperm midpiece morphology	1
abnormal sperm mitochondrial sheath morphology	1
abnormal mitochondrial ATP synthesis coupled electron transport	1
abnormal mitochondrial crista morphology	1
abnormal X-Y chromosome synapsis during male meiosis	1
increased male germ cell apoptosis	1
impaired double-strand DNA break repair	1
decreased sperm progressive motility	1
impaired binding of sperm to zona pellucida	1
impaired sperm migration in female genital tract	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
Pongo abelii	Q5R5E8	99.3%	Diamond
Macaca fascicularis	O46644	94.2%	Diamond
Macaca mulatta	P12545	93.1%	Diamond
Capra hircus	P10626	90.0%	Diamond
Felis catus	Q5R1M5	89.9%	Diamond
Canis lupus familiaris	Q867B0	89.9%	Diamond
Sus scrofa	P00772	89.5%	Diamond
Bos taurus	Q28153	87.9%	Diamond
Oryctolagus cuniculus	P48038	76.7%	Diamond
Ovis aries	Q9GL10	76.5%	Diamond
Cavia porcellus	Q04962	73.2%	Diamond
Salmo salar	Q7SIG3	70.9%	Diamond
Bombus ignitus	B5U2W0	67.2%	Diamond
Bombus pensylvanicus	Q7M4I3	67.2%	Diamond
Drosophila melanogaster	Q9VWU1	66.9%	Diamond
Olivierus martensii	P0C8M2	59.5%	Diamond
Galleria mellonella	A0A6J1W8N1	50.0%	Diamond
Anopheles gambiae	A0A1S4H5M5	48.4%	Diamond
Holotrichia diomphalia	Q9GRW0	47.7%	Diamond
Meleagris gallopavo	Q2UVH8	44.9%	Diamond
Apis mellifera	Q8MQS8	43.2%	Diamond
Tachypleus tridentatus	Q27081	41.5%	Diamond
Halocynthia roretzi	Q966V2	38.5%	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
TMT1A	protein-coding	25840
SLC11A2	protein-coding	4891
HIGD1C	protein-coding	613227
ATF1-AS1	ncRNA	124902932
ATF1	protein-coding	466
DIP2B	protein-coding	57609
LETMD1	protein-coding	25875
CSRNP2	protein-coding	81566

Protein

Protein identifiers

Transmembrane protease serine 12 — Q86WS5 (reviewed: Q86WS5)

All UniProt accessions (2): F8WBX2, Q86WS5

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

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

Protein evidence: Evidence at protein level

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)

Position	Role
122	charge relay system
171	charge relay system
268	charge relay system

Disulfide bonds (4)

Type	Positions
Disulfide bond	107–123, 206–274, 237–253, 264–294

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	219, 249

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: 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 (7): acrosome assembly (GO:0001675), spermatogenesis (GO:0007283), single fertilization (GO:0007338), protein processing (GO:0016485), positive regulation of sperm capacitation (GO:1902492), proteolysis (GO:0006508), 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 (3): acrosomal vesicle (GO:0001669), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410)

GO top-level categories

29 GO namespaces:

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
fertilization	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
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
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

showing 15 of 832 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS12	RNF215	Q9Y6U7	650
TMPRSS12	PRSS37	A4D1T9	645
TMPRSS12	ERGIC2	Q96RQ1	549
TMPRSS12	ZNF10	P21506	548
TMPRSS12	DRC9	Q9H095	479
TMPRSS12	TPPP2	P59282	470
TMPRSS12	BCCIP	Q9P287	447
TMPRSS12	PGAM2	P15259	370
TMPRSS12	SYCP1	Q15431	370
TMPRSS12	KLC3	Q6P597	370
TMPRSS12	AGFG1	P52594	370
TMPRSS12	GPR150	Q8NGU9	364
TMPRSS12	OR6M1	Q8NGM8	360
TMPRSS12	SSMEM1	Q8WWF3	355
TMPRSS12	HEMGN	Q9BXL5	354

IntAct

Human interaction partners of TMPRSS12 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
FZD6	association	0.530	2
SOAT1	association	0.530	1
NPC1	association	0.350	1

BioGRID (33 interactions; top human partners by supporting records): ABCA3 (Affinity Capture-MS; 2 records), ALG9 (Affinity Capture-MS; 2 records), DPY19L4 (Affinity Capture-MS; 2 records), FZD6 (Affinity Capture-MS; 2 records), PIGB (Affinity Capture-MS; 2 records), PKD2 (Affinity Capture-MS; 2 records), POMT1 (Affinity Capture-MS; 2 records), SIDT2 (Affinity Capture-MS; 2 records), SLC47A1 (Affinity Capture-MS; 2 records), SNCA (Affinity Capture-MS; 2 records), SOAT1 (Affinity Capture-MS; 2 records), AMIGO1 (Affinity Capture-MS), BRCA1 (Two-hybrid), CLPTM1 (Affinity Capture-MS), FZD2 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for TMPRSS12: 65 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 10 predictions of 464):

Position(s)	Effect	Δscore	Sites
12:50843130	donor_gain	0.9900
12:50843134	donor_gain	0.9900
12:50843138	donor_gain	0.9900
12:50843152	donor_gain	0.9900
12:50843179	donor_gain	0.9900
12:50843005	donor_gain	0.9800
12:50858855	donor_gain	0.9800
12:50843049	donor_gain	0.9700
12:50843080	donor_gain	0.9700
12:50843095	donor_gain	0.9600

AlphaMissense

536 missense substitutions predicted likely pathogenic (of 2,269 scored), across 131 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
D267	8	0.976	0.989
D171	8	0.957	0.984
D262	8	0.936	0.973
H122	8	0.884	0.943
S268	8	0.865	0.978
C253	7	0.986	0.994
C123	7	0.982	0.992
C264	7	0.981	0.990
C237	7	0.976	0.992
C206	7	0.973	0.991
W211	7	0.973	0.995
C274	7	0.971	0.988
C294	7	0.971	0.988
C107	7	0.966	0.985
C191	7	0.962	0.977
W91	7	0.945	0.991
W133	7	0.933	0.987
F163	7	0.920	0.979
W312	7	0.903	0.984
S94	7	0.899	0.989

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene `` | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST90011898_63	Alanine aminotransferase levels	1e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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)

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