A functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system

Schlecht, Ulrich; Suresh, Sundari; Xu, Weihong; Aparicio, Ana Maria; Chu, Angela; Proctor, Michael J; Davis, Ronald W; Scharfe, Curt; St Onge, Robert P

doi:10.1186/1471-2164-15-263

BMC Genomics

Table 1 Human disease genes putatively associated with copper imbalance

From: A functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system

Yeast gene	Human gene	% ident.	Subcellular localization	Biological function	OMIM	Clinical phenotype
CCC2	ATP7A	23	Golgi apparatus, Plasma membrane	Cu ion transport across membranes	309400	Menkes disease (copper deficiency)
CCC2	ATP7B	24	Golgi apparatus, Mitochondria	Cu ion transport across membranes	277900	Wilson disease (copper overload)
ADK1	AK2	54	Mitochondrial inter-membrane space	Energy and nucleotide metabolism	267500	Immunodeficiency, sensorineural deafness
COX12	COX6B1	42	Mitochondrial inter-membrane space	Energy metabolism, respiratory chain complex	220110	Encephalopathy, growth retardation, vision loss
VMA2	ATP6V1B1	73	Endomembrane, plasma membrane	Vacuolar proton-translocating ATPase	267300	Renal tubular acidosis, sensorineural deafness
HFA1	ACACA	38	Mitochondria, cytoplasm	Fatty acid biosynthesis	613933	Encephalopathy, growth retardation, myopathy
GEF1	CLCN5	30	Endosome membrane, lysosomal membrane	Chloride channels and ion transporter	300009	Renal tubular disease, kidney stones
GEF1	CLCN7	20		Chloride channels and ion transporter	166600	Osteosclerosis, multiple fractures, vision loss
VPS33	VPS33B	23		Protein transport, membrane fusion	208085	Arthrogryposis, renal dysfunction, cholestasis
NHX1	SLC9A9	27	Endosome membrane	pH regulation, ion transport	613410	Autism, seizures
NHX1	SLC9A6	26	Endosome membrane	pH regulation, ion transport	300243	Mental retardation, seizures, ataxia
APS1	AP1S2	51	Golgi apparatus	AP-1 adaptor complex, protein transport, vesicular trafficking	300630	Mental retardation, cerebral calcifications
APS1	AP4S1	26			614067	Spastic paraplegia, mental retardation
APL2	AP4B1	22			614066
APM1	AP4M1	24			612936
ARL1	ARL6	39		Protein transport, metal ion binding, membrane trafficking	209900	Mental retardation, obesity, retinopathy
ARL3	ARL13B	13		Protein transport, metal ion binding, membrane trafficking	612291	Cerebral malformation, mental retardation
COG6	COG6	19		Oligomeric Golgi complex, vesicular transport	606977	Vitamin K deficiency, intracranial bleedings
APL6	AP3B1	20		AP-3 adaptor complex, protein transport	608233	Platelet defect, albinism, immunodeficiency
ERG24	DHCR7	27	Endoplasmatic reticulum	Cholesterol biosynthesis, sterol metabolism	270400	Mental retardation, congenital malformation
	LBR	27	Nuclear membrane		215140	Skeletal dysplasia, leukocyte disorder

Twenty-one human disease genes which have a yeast orthologue (% identity of human protein in column 3) that, when deleted, produced a respiratory fitness defect that was specifically rescued by copper supplementation. The gene products of the 21 disease genes have distinct functions and subcellular localizations [64], while mutations in these genes are typically associated with neurologic, musculoskeletal and hematologic disease phenotypes resembling those of copper deficiency (http://omim.org/).

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ISSN: 1471-2164

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