Table 3.

Summary of monogenic diseases that may be amenable to treatment based on homing endonuclease-induced double-strand break homologous recombination

Disease	Gene	OMIMa	Chromosome	Frequency	Inheritance	References
Acute intermittent porphyria	Porphobilinogen deaminase	609806	11q23	>104	Autosomal dominant	[174]
Congenital erythropoietic porphyria	Uroporphyrinogen cosynthase	263700	10q25	>105	Autosomal recessive	[175, 176]
Porphyria cutanea tarda	Uroporphyrinogen decarboxylase	176100	1p34	<104	Autosomal dominant	[177]
Hereditary coproporphyria	Coproporphyrinogen oxidase	612732	3q12	>105	Autosomal dominant	[178]
Variegate porphyria	Protoporphyrinogen oxidase	600923	1q22	>105	Autosomal dominant	[179]
Erythropoietic protoporphyria	Ferrochelatase	612386	18q21	>105	Autosomal dominant	[180]
α Thalassemia	α Hemoglobin (HBA1)	141800	16p13	<104	Autosomal recessive	[181]
α Thalassemia	α Hemoglobin (HBA2)	141850	16p13	<104	Autosomal recessive	[182]
β Thalassemia	β Hemoglobin (HBB)	141900	11p15	<104	Autosomal recessive	[183]
Sickle cell anemia	β Hemoglobin (HBB)	603903	11p15	<104	Autosomal recessive	[184]
Familial mediterranean fever	Familial mediterranean fever (MEFV)	608107	16p13	<104 In Mediterranean people	Autosomal dominant	[185]
Severe combined immunodeficiency (SCID)	Adenosine deaminase (ADA)	608958	20q13	<105	Autosomal recessive	[186, 187]
Severe combined immunodeficiency (SCID)	Interleukin 2 receptor gamma (IL2RG)	308380	Xq13	>105	X-linked	[188]
Severe combined immunodeficiency (SCID). Omenn syndrome	Recombination-activating gene (RAG1)	179615	11p13	>104	Autosomal recessive	[189]
Severe combined immunodeficiency (SCID). Omenn syndrome	Recombination-activating gene (RAG2)	179616	11p13	>104	Autosomal recessive	[190]
Severe combined immunodeficiency (SCID)	Janus kinase 3 (JAK3)	600173	19p13	<104	Autosomal recessive	[191]
Chronic myeloid leukemia	Breakpoint cluster region	151410	22q11	<105	Somatic	[192]
Chronic granulomatous disease	CYBB (gp91-phox), cytochrome b(-245) beta subunit	300481	Xp21	<105	X-linked	[193]
Chronic granulomatous disease	CYBA (p22-phox), cytochrome b(-245) alpha subunit	608508	16q24	<105	Autosomal recessive	[194]
Chronic granulomatous disease	NCF1 (p47-phox), neutrophil cytosolic factor 1	608512	7q11	<105	Autosomal recessive	[195]
Chronic granulomatous disease	NCF2 (p67-phox), neutrophil cytosolic factor 2	233710	1q25	<105	Autosomal recessive	[196]
Hemophilia A	Coagulation factor VIII	306700	Xq28	<104	X-linked	[197]
Hemophilia B	Coagulation factor IX	300746	Xq27	<105	X-linked	[198]
Fanconi anemia	FANCA-N, fanconi anemia complementation group	227650	16q24, Xp22, 9q22, 13q12, 3p25, 6p22, 11p15	>105	Autosomal recessive, X-linked (FANCB)	[199]
Paroxysmal nocturnal hemoglobinuria	Phosphatidylinositol glycan, class A (PIGA)	311770	Xp22	Unknown	Somatic (do not inherited)	[200]
Immunodeficiency with hyper-IgM	CD40 antigen ligand	300386	Xq26	<105	X-linked	[201]
Autoimmune polyendocrinopathy ectodermal dystrophy	Autoimmune regulator (AIRE)	607358	21q22	>105	Autosomal recessive	[202, 203]
Malignant melanoma	Cyclin-dependent kinase inhibitor 2A (CDKN2A)	600160	9p21	>105	Autosomal recessive	[204, 205]
Xeroderma pigmentosum	Xeroderma pigmentosum, complementation group C (XPC)	278720	3p25	<105	Autosomal recessive	[206, 207]
Xeroderma pigmentosum	Xeroderma pigmentosum, complementation group E (XPE)	278740	11p12	<105	Autosomal recessive	[208]
Familial hypercholesterolemia	Low density lipoprotein receptor (LDLR)	606945	19p13	>104	Autosomal dominant	[209]
Urea cycle disorder	Ornithine carbamoyltransferase (OTC)	300461	Xp21	>105	X-linked	[210]
Lesch-Nyhan syndrome	Hypoxanthine guanine phosphoribosyltransferase 1 (HPRT1)	308000	Xq26	<105	X-linked	[211]
Human tumors	Tumor protein p53 (TP53)	191170	17p13	>104	Somatic	[152, 153]

^aThe Online Mendelian Inheritance in Man (OMIM) (http://www.ncbi.nlm.nih.gov/sites/entrez?db=OMIM&itool=toolbar) number is included for more information