TMPRSS12

protein-coding

transmembrane serine protease 12, the group of Type II transmembrane serine proteases

Gene summary

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. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_182559.3

Inheritance

—

ClinVar variants

U:54B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr12:50,842,920-50,887,884

External References & Databases

Ensembl (ENSG00000186452)

Transcript & Mutation Effects

hg38 • Region Span ~45.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMPRSS12 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 60

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182559.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			51 clinvar	8 clinvar		59
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	54	9	0	63

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182559.3	RefSeq	NP_872365.2	5	MANE Select
ENST00000398458.4	Ensembl	ENSP00000381476.3	5	MANE Select
ENST00000551456.5	Ensembl	ENSP00000447259.1	4	Standard
ENST00001137983.1	Ensembl	ENSP00000812068.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

serine-type endopeptidase activity

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398458
Coding exons: 5
Length: 44965
Individuals with no LoFs: 124633
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 124666
p: 0.000132

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.00472	178	178	0.999	0.00000945	2206
Missense (PolyPhen)		35	43.524	0.80415		572
Synonymous	1.02	58	68.8	0.843	0.00000392	684
Loss of Function	0.564	9	11.0	0.817	5.28e-7	155

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.00039	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000065	0.000062	rare
South Asian	0.00025	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0867

Intolerance Scores

RVIS EVS: 0.82
RVIS percentile EVS: 87.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.133

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium