Human hereditary diseases of proteolysis

Proteases are a group of enzymes implicated in numerous human pathologies, including inflammatory diseases, cancer, cardiovascular diseases,...According to this table, more than 10% of the human protease genes are involved in human hereditary pathologies. These 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 AnimalModel Refs
angiotensin converting enzyme ACE 17q23 Renal tubular dysgenesis 106180 R Loss KO resembles disease -
angiotensin converting enzyme ACE 17q23 Renal tubular dysgenesis 106180 R Loss KO resembles disease -
ADAM10 ADAM10 15q21 Late-onset Alzheimer's disease 602192 Incomplete Gain/Loss - -
ADAM10 ADAM10 15q21 Reticulate acropigmentation of Kitamura 615537 D Loss -
ADAM17 ADAM17 2p25 Inflammatory skin and bowel disease 603639 R Loss KO partially resembles disease
ADAM9 ADAM9 8p11 Cone-rod dystrophy 612775 - Loss KO resembles disease
ADAMTS-10 ADAMTS10 19p13 Weill-Marchesani syndrome 277600 R Loss -
ADAMTS-13 ADAMTS13 9q34 Thrombotic thombocytopenic purpura 274150 R Loss -
ADAMTS-17 ADAMTS17 15q26 Weill-Marchesani syndrome 277600 R Loss -
ADAMTS-18 ADAMTS18 16q23 Knobloch syndrome 267750 R (Loss) -
procollagen I N-endopeptidase ADAMTS2 5q23 Ehlers-Danlos syndrome type VIIC 225410 R Loss KO resembles disease
Afg3-like protein 2 AFG3L2 18p11 Dominant hereditary ataxia SCA28 610246 D Loss -
Afg3-like protein 2 AFG3L2 18p11 Spastic Ataxia-Neuropathy Syndrome 604581 R Loss KO exhibits a severe neurodegenerative phenotype
glycosylasparaginase AGA 4q34 Aspartylglucosaminuria 208400 R Loss KO resembles disease
UDP-N-acetylglucosaminyltransferase subunit ALG13 Xq23 Congenital disorder of glycosylation, type Is 300884 R Loss -
acid ceramidase ASAH1 8p22 Spinal Muscular Atrophy With Progressive Myoclonic Epilepsy 159950 R Loss -
acid ceramidase ASAH1 8p22 Farber lipogranulomatosis 228000 R Loss -
aspartoacylase (np) ASPA 17p13 Canavan disease 271900 R Loss KO resembles disease
procollagen C-proteinase BMP1 8p21 Osteogenesis imperfecta, type III 259420 R Loss -
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 1 CAPN1 11q13 Hereditary spastic paraplegia 182600 R Loss KO resembles disease 27153400
Calpain 1 CAPN1 11q13 Cerebellar ataxia 164400 D Loss KO resembles disease 27320912
calpain 10 CAPN10 2q37 Autosomal recessive intellectual disability (ARID) 605286 R (Loss) -
calpain 3 CAPN3 15q15 Limb-girdle muscular dystrophy type 2A 253600 R Loss KO resembles disease
calpain 5 CAPN5 11q13 Neovascular Inflammatory Vitreoretinopathy 193235 D Loss KO does not resemble disease 25994508
caspase-10 CASP10 2q33 Autoimmune lymphoproliferative syndrome (II) 603909 D,R Loss No mouse ortholog
caspase-2 CASP2 11q22 Autosomal recessive intellectual disability (ARID) 600639 R (Loss) -
caspase-8 CASP8 2q33 Autoimmune lymphoproliferative syndrome (I) 601859 R Loss KO embryonic lethality
caspase-9 CASP9 1p36 Familial Tumor Syndrome 151623 D Loss 27935156
complement factor B CFB 6p21 Hemolytic uremic syndrome, atypical, susceptibility to, 4 612924 D Gain -
complement factor B CFB 6p21 Immunodeficiency 615561 R Loss -
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 F CTSF 11q13 Type B Kufs disease 615362 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 Hirschsprung disease, cardiac defects, and autonomic dysfunction 613870 D Loss KO partially resembles disease 9915973
DINE peptidase ECEL1 2q37 Distal arthrogryposis 605896 R Loss - 23236030
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
family with sequence similarity 111, A FAM111A 11q12 Kenny-Caffey syndrome 127000 D (Loss) -
family with sequence similarity 111, A FAM111A 11q12 Osteocraniostenosis 602361 D (Loss) -
family with sequence similarity 111, B FAM111B 11q12 Weary hereditary sclerosing poikiloderma 173700 D (Gain) -
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 Essential tremor 190300 D Loss - 25422467
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 -
PIM1 endopeptidase LONP1 19p13 CODAS syndrome 600373 R Loss - 25574826
mannan-binding serine protease 1 MASP1 3q29 3MC ?term=3MC 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
MT1-MMP MMP14 14q11 Winchester syndrome 277950 R Loss KO partially resembles disease
gelatinase A MMP2 16q13 Multicentric osteolysis with arthritis 605156 R Loss KO does not resemble disease
enamelysin MMP20 11q22 Amelogenesis imperfecta 301200 R Loss KO resembles disease
Matrix Metallopeptidase 21 MMP21 10q26 Heterotaxia ?term=heterotaxy R Loss Knockin mice resembles disease, Knockdown Zebra fish partially resemble disease 26437028
gelatinase B MMP9 20q13 Metaphyseal anadysplasia 613073 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 -
O-sialoglycoprotein endopeptidase OSGEP 14q11 Galloway–Mowat syndrome 251300 R Loss KO resembles disease 28805828
Hin-1/OTU domain containing 4 OTUD4 4q31 Cerebellar Ataxia and Hypogonadotropic Hypogonadism 212840 R Loss Zebra fish morpholino model partially resembles disease
OTU domain containing 6B OTUD6B 8q21 Intellectual Disability Syndrome Associated with Seizures and Dysmorphic Features 612021 R Loss KO resembles disease 28343629
OTULIN OTULIN 5p15 OTULIN-related autoin- flammatory syndrome (ORAS) 617099 R Loss KO resembles disease 27523608
pappalysin-2 PAPPA2 1q25 Growth failure syndrome - R Loss - 26902202
presenilins-assoc. rhomboid like PARL 3q27 Parkinson's disease 168600 R 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 -
protease, serine, 56 PRSS56 2q37 Microphtalmia, isolated 6 613517 R Loss -
enteropeptidase PRSS7 21q21 Enteropeptidase deficiency 226200 R Loss -
presenilin 1 PSEN1 14q24 Alzheimer type 3 104311 D Gain Transgenic models partially resemble disease
presenilin 1 PSEN1 14q24 Familial acne inversa 142690 D Loss Transgenic models partially resemble disease
presenilin 2 PSEN2 1q42 Alzheimer type 4 600759 D Gain Transgenic models partially resemble disease
proteasome alpha 3 subunit PSMA3 14q23 CANDLE/PRAAS 256040 R Loss - 26524591
proteasome beta 4 subunit PSMB4 1q21 CANDLE/PRAAS 256040 R Loss - 26524591
proteasome catalytic subunit 3i PSMB8 6p21 CANDLE/PRAAS 256040 R Loss - 26524591
proteasome catalytic subunit 1i PSMB9 6q21 CANDLE/PRAAS 256040 R Loss - 26524591
reelin RELN 7q22 Lissencephaly syndrome 257320 R Loss Reeler mouse resembles disease
renin REN 1q32 Renal tubular dysgenesis 179820 R Loss -
rhomboid 5 homolog 2 RHBDF2 17q25 Tylosis with esophageal cancer 148500 D Mislocalization -
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
AMSH/STAMBP STAMBP 2p13 Microcephaly-capillary malformation syndrome 614261 R Loss - 23542699
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 -
transmembrane Ser-protease 4 TMPRSS4 11q23 Autosomal Recessive Cerebral Atrophy 606565 R Loss -
matriptase 2 TMPRSS6 22q12 Iron-refractory iron deficiency anemia 609862 - Loss -
A20, TNFa-induced protein 3 TNFAIP3 6q23 Early-onset autoinflammatory disease - D Loss Different truncating mutations 26642243
tripeptidyl-peptidase II TPP2 13q33 Evans syndrome 601608 R Loss Transgenic models partially resemble disease
Ttryptase alpha/beta 1 TPSAB1 16p13 Multisystem disorder 191080 D Gain (Increased copy number) - 27749843
ubiquitin C-terminal hydrolase 1 UCHL1 4p14 Parkinson disease type V 191342 D Loss Gad mouse resembles disease
UCR2 UQCRC2 16p12 Mitochondrial Complex III Deficiency 615160 R Loss -
Ubiquitin Specific Peptidase 18 USP18 22q11 Pseudo-TOR CH syndrome 251290 R Loss - 27325888
USP26 USP26 Xq26 Sertoli cell-only syndrome 305700 R Loss -
USP9X USP9X Xp11 X-Linked intellectual disability 300919 R Loss KO model partially resembles disease 24607389
USP9Y USP9Y Yq11 Azoospermia and hypospermatogenesis 415000 D Loss -
aminopeptidase P homologue XPNPEP3 22q13 Nephronophthisis-like nephropathy 613159 R Loss Suppression model phenocopies disease
YME1 like 1 ATPase YME1L1 10p14 Mitochondriopathy with optic atrophy and mitochondrial network fragmentation 607472 R Loss KO resembles disease 27495975