Proteases are a group of enzymes implicated in numerous human pathologies, including inflammatory diseases, cancer, cardiovascular diseases,... We have catalogued a total of 80 human hereditary diseases caused by mutations in protease-coding genes, which implies that more than 10% of the human protease genes are involved in human pathologies. They are classified in three groups: loss of function, gain of function, and an heterogeneous group including non-protease homologs (np), putative proteases, and hedgehog proteins with only autoprocessing activity. Type of inheritance is indicated by R (recessive) or D (dominant).
| Protease |
Gene |
Locus |
Disease |
OMIM |
Inher. |
Function |
Animal Model |
| angiotensin converting enzyme |
ACE |
17q23 |
Renal tubular dysgenesis |
106180 |
R |
Loss |
KO resembles disease |
| aminoacylase 1 |
ACY1 |
3p21 |
Aminoacylase 1 deficiency |
104620 |
R |
Loss |
- |
| ADAM9 |
ADAM9 |
8p11 |
Cone-rod dystrophy |
612775 |
- |
Loss |
KO resembles disease |
| ADAM10 |
ADAM10 |
15q21 |
Late-onset Alzheimer's disease |
602192 |
Incomplete |
Gain/Loss |
- |
| ADAMTS-10 |
ADAMTS10 |
19p13 |
Weill-Marchesani syndrome |
277600 |
R |
Loss |
- |
| ADAMTS-13 |
ADAMTS13 |
9q34 |
Thrombotic thombocytopenic purpura |
274150 |
R |
Loss |
- |
| AGAMTS-17 |
ADAMTS17 |
15q26 |
Weill-Marchesani syndrome |
277600 |
R |
Loss |
- |
| procollagen I N-endopeptidase |
ADAMTS2 |
5q23 |
Ehlers-Danlos syndrome type VIIC |
225410 |
R |
Loss |
KO resembles disease |
| glycosylasparaginase |
AGA |
4q34 |
Aspartylglucosaminuria |
208400 |
R |
Loss |
KO resembles disease |
| aspartoacylase (np) |
ASPA |
17p13 |
Canavan disease |
271900 |
R |
Loss |
KO resembles disease |
| complement factor B |
BF |
6p21 |
Atypical hemolytic uremic syndrome |
235400 |
R |
Gain |
- |
| complement component C1r |
C1R |
12p13 |
C1r deficiency |
216950 |
R |
Loss |
- |
| complement component C1s |
C1S |
12p13 |
C1s deficiency |
120580 |
R |
Loss |
- |
| complement component 2 |
C2 |
6p21 |
C2 deficiency |
217000 |
R |
Loss |
Guinea pig model resembles disease |
| calpain 3 |
CAPN3 |
15q15 |
Limb-girdle muscular dystrophy type 2A |
253600 |
R |
Loss |
KO resembles disease |
| caspase-10 |
CASP10 |
2q33 |
Autoimmune lymphoproliferative syndrome (II) |
603909 |
D,R |
Loss |
No mouse ortholog |
| caspase-8 |
CASP8 |
2q33 |
Autoimmune lymphoproliferative syndrome (I) |
601859 |
R |
Loss |
KO embryonic lethality |
| tripeptidyl-peptidase I |
CLN2 |
11p15 |
Neuronal ceroid lipofuscinosis |
204500 |
R |
Loss |
- |
| carboxypeptidase A6 |
CPA6 |
8q13 |
Duane retraction syndrome |
126800 |
R |
Loss |
- |
| carboxypeptidase E |
CPE |
4q33 |
Hyperproinsulinemia and diabetes |
125853 |
R |
Loss |
Fat mouse resembles disease |
| carboxypeptidase N |
CPN1 |
10q24 |
Carboxypeptidase N deficiency |
212070 |
R |
Loss |
- |
| chymotrypsin C |
CTRC |
1p36 |
Hereditary pancreatitis |
167800 |
D |
Loss |
- |
| cathepsin C |
CTSC |
11q14 |
Papillon-Lefevre and Haim-Munk syndromes |
245000 |
R |
Loss |
KO does not resemble disease |
| cathepsin D |
CTSD |
11p15 |
Neuronal ceroid lipofuscinosis |
610127 |
R |
Loss |
KO resembles disease |
| cathepsin K |
CTSK |
1q21 |
Pycnodysostosis |
265800 |
R |
Loss |
KO resembles disease |
| cylindromatosis protein |
CYLD1 |
16q12 |
Cylindromatosis |
132700 |
D |
Loss |
- |
| complement factor D |
DF |
19p13 |
DF deficiency |
134350 |
R |
Loss |
KO resembles disease |
| desert hedgehog protein |
DHH |
12q13 |
Partial gonadal dysgenesis |
607080 |
R |
Loss |
KO resembles disease |
| DJ-1 (putative protease) |
DJ-1 |
1p36 |
Parkinson disease type VII |
606324 |
R |
Loss |
KO partially resembles disease |
| dihydropyrimidinase (np) |
DPYS |
8q22 |
Dihydropyrimidinase deficiency |
222748 |
R |
Loss |
- |
| endothelin-converting enzyme 1 |
ECE1 |
1p36 |
Hirschprung disease |
142623 |
D |
Loss |
KO partially resembles disease |
| neutrophil elastase |
ELA2 |
19p13 |
Cyclic neutropenia |
162800 |
D |
Gain |
KO more susceptible to bacterial sepsis |
| coagulation factor Xa |
F10 |
13q34 |
Factor X deficiency |
227600 |
R |
Loss |
KO embryonic lethality or fatal neonatal bleeding |
| coagulation factor Xia |
F11 |
4q35 |
Factor XI deficiency |
264900 |
R |
Loss |
Cattle and dog models resemble disease |
| coagulation factor XIIa |
F12 |
5q35 |
Factor XII deficiency |
234000 |
R |
Loss |
- |
| coagulation factor XIIa |
F12 |
5q35 |
Hereditary angioedema type III |
610619 |
D |
Gain |
- |
| thrombin |
F2 |
11p11 |
Hyperprothrombinemia / hypoprothombinemia |
176930 |
D/R |
Loss |
KO resembles disease |
| coagulation factor VIIa |
F7 |
13q34 |
Factor VIIa deficiency |
227500 |
R |
Loss |
KO lethal, partially resembles disease |
| coagulation factor Ixa |
F9 |
Xq27 |
Hemophilia B |
306900 |
R |
Loss |
Mouse and dog models resemble disease |
| FACE1/ZMPSTE24 |
FACE1 |
1p34 |
Progeria, Mandibuloacral dysplasia |
248370 |
R |
Loss |
KO resembles disease |
| gamma-glutamyltransferase 1 |
GGT1 |
22q11 |
Gamma-glutamyltransferase deficiency |
231950 |
R |
Loss |
- |
| haptoglobin-1 (np) |
HP |
16q22 |
Anhaptoglobinemia |
140100 |
R |
Loss |
KO resembles disease |
| osteoblast serine protease |
HTRA1 |
10q26 |
CARASIL |
600142 |
- |
Loss |
- |
| Omi/HtrA2/PRSS25 |
HTRA2 |
2p12 |
Parkinson disease |
168600 |
D |
Loss |
mnd2 mouse resembles disease |
| complement factor I |
IF |
4q25 |
CFI deficiency |
217030 |
R |
Loss |
- |
| indian hedgehog protein |
IHH |
2q35 |
Brachydactyly type A1 |
112500 |
D |
Loss |
KO resembles disease |
| mitoch. inner membrane protease 2 |
IMMP2L |
7q31 |
Gilles de la Tourette syndrome |
137580 |
D |
Loss |
- |
| Kell blood-group protein |
KEL |
7q35 |
Kell blood group antigen |
110900 |
R |
Loss |
- |
| kallikrein 4 |
KLK4 |
19q13 |
Hypomaturation amelogenesis imperfecta |
204700 |
R |
Loss |
- |
| plasma kallikrein |
KLKB1 |
4q35 |
Prekallikrein deficiency |
229000 |
R |
Loss |
- |
| mannan-binding serine protease 2 |
MASP2 |
1p36 |
MASP2 deficiency |
605102 |
R |
Loss |
- |
| S2P protease |
MBTPS2 |
Xp22 |
Ichthyosis follicularis, atrichia, and photophobia syndrome (IFAP) |
308205 |
- |
Loss |
- |
| ataxin 3 |
MJD1 |
14q32 |
Machado-Joseph disease |
109150 |
D |
(Gain) |
Transgenic models partially resemble disease |
| neprilysin |
MME |
3q26 |
Fetomaternal alloimmunisation |
120520 |
R |
Loss |
- |
| collagenase 3 |
MMP13 |
11q22 |
Spondyloepimetaphyseal dysplasia |
602111 |
D |
(Gain) |
KO resembles disease |
| gelatinase A |
MMP2 |
16q13 |
Multicentric osteolysis with arthritis |
605156 |
R |
Loss |
KO does not resemble disease |
| gelatinase B |
MMP9 |
20q13 |
Metaphyseal anadysplasia |
613073 |
R |
Loss |
KO resembles disease |
| enamelysin |
MMP20 |
11q22 |
Amelogenesis imperfecta |
301200 |
R |
Loss |
KO resembles disease |
| matriptase |
MTSP1 |
11q24 |
Ichthyosis with hypotrichosis |
606797 |
R |
Loss |
KO resembles disease |
| nasal embryonic LHRH factor |
NELFnp |
9q34 |
Kallmann syndrome |
608137 |
- |
Loss |
- |
| proprotein convertase 1 |
PCSK1 |
5q15 |
Obesity |
600955 |
R |
Loss |
KO does not resemble disease |
| proprotein convertase 5 |
PCSK5 |
9q21 |
VACTERL/Caudal regression/Currarino syndrome-like |
192350 |
R |
Loss |
KO resembles disease |
| proprotein convertase 9 |
PCSK9 |
1p32 |
Hyperlipoproteinemia type III |
144400 |
D |
(Gain) |
- |
| X-Pro dipeptidase |
PEPD |
19q13 |
Prolidase deficiency |
170100 |
R |
Loss |
- |
| PHEX endopeptidase |
PHEX |
Xp22 |
X-linked hypophosphatemia |
307800 |
D |
Loss |
Hyp mouse resembles disease |
| plasmin |
PLG |
6q26 |
Thrombophilia and ligneous conjunctivitis |
173350 |
R |
Loss |
KO resembles disease |
| lysosomal carboxypeptidase A |
PPGB |
20q13 |
Galactosialidosis |
256540 |
R |
Loss |
KO resembles disease |
| prolyl endopeptidase-like |
PREPL |
2p21 |
Hypotonia-cystinuria syndrome |
606407 |
R |
Loss |
- |
| protein C |
PROC |
2q21 |
Thrombophilia |
176860 |
D/R |
Loss |
KO resembles disease |
| cationic trypsin |
PRSS1 |
7q35 |
Hereditary pancreatitis / trypsin deficiency |
167800 |
D/R |
Gain/Loss |
- |
| neurotrypsin |
PRSS12 |
4q28 |
Nonsyndromic mental retardation |
249500 |
R |
Loss |
- |
| enteropeptidase |
PRSS7 |
21q21 |
Enteropeptidase deficiency |
226200 |
R |
Loss |
- |
| presenilin 1 |
PSEN1 |
14q24 |
Alzheimer type 3 |
104311 |
D |
Gain |
Transgenic models partially resemble diseasee |
| presenilin 2 |
PSEN2 |
1q42 |
Alzheimer type 4 |
600759 |
D |
Gain |
Transgenic models partially resemble disease |
| reelin |
RELN |
7q22 |
Lissencephaly syndrome |
257320 |
R |
Loss |
Reeler mouse resembles disease |
| renin |
REN |
1q32 |
Renal tubular dysgenesis |
179820 |
R |
Loss |
- |
| sonic hedgehog protein |
SHH |
7q36 |
Holoprosencephaly type 3 |
142945 |
D |
Loss |
KO resembles disease |
| paraplegin |
SPG7 |
16q24 |
Spastic paraplegia |
607259 |
R |
Loss |
KO resembles disease |
| transferrin receptor 2 protein (np) |
TFR2 |
7q22 |
Hemochromatosis type 3 |
604250 |
R |
Loss |
KO resembles disease |
| transmembrane protease, serine 3 |
TMPRSS3 |
21q22 |
Deafness |
605316 |
R |
Loss |
- |
| matriptase 2 |
TMPRSS6 |
22q12 |
Iron-refractory iron deficiency anemia |
609862 |
- |
Loss |
- |
| ubiquitin C-terminal hydrolase 1 |
UCHL1 |
4p14 |
Parkinson disease type V |
191342 |
D |
Loss |
Gad mouse resembles disease |
| USP26 |
USP26 |
Xq26 |
Sertoli cell-only syndrome |
305700 |
R |
Loss |
- |
| USP9Y |
USP9Y |
Yq11 |
Azoospermia and hypospermatogenesis |
415000 |
D |
Loss |
- |