Human hereditary diseases of proteolysis. Proteases are a group of enzymes implicated in numerous human pathologies, including inflammatory diseases,
cancer, cardiovascular diseases,... We have catalogued a total of 76 human hereditary diseases caused by mutations in protease-coding genes, what 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	-
procollagen I N-endopeptidase	ADAMTS2	5q23	Ehlers-Danlos syndrome type VIIC	225410	R	Loss	KO resembles disease
ADAMTS-10	ADAMTS10	19p13	Weill-Marchesani syndrome	277600	R	Loss	-
ADAMTS-13	ADAMTS13	9q34	Thrombotic thombocytopenic purpura	274150	R	Loss	-
glycosylasparaginase	AGA	4q34	Aspartylglucosaminuria	208400	R	Loss	KO resembles disease
aspartoacylase (np)	ASPA	17p13	Canavan disease	271900	R	Loss	KO resembles disease
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-8	CASP8	2q33	Autoimmune lymphoproliferative syndrome (I)	601859	R	Loss	KO embryonic lethality
caspase-10	CASP10	2q33	Autoimmune lymphoproliferative syndrome (II)	603909	D,R	Loss	No mouse ortholog
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 B	BF	6p21	Atypical hemolytic uremic syndrome	235400	R	Gain	-
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
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	-
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
enamelysin	MMP20	11q22	Amelogenesis imperfecta	301200	R	Loss	KO resembles disease
matriptase	MTSP1	11q24	Ichthyosis with hypotrichosis	606797	R	Loss	KO resembles disease
proprotein convertase 1	PCSK1	5q15	Obesity	600955	R	Loss	KO does not resemble 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
USP9Y	USP9Y	Yq11	Azoospermia and hypospermatogenesis	415000	D	Loss	-
USP26	USP26	Xq26	Sertoli cell-only syndrome	305700	R	Loss	-
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This page was last modified: 03-Feb-07