Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

ABCA4

contributors: shn/mct - updated : 30-05-2018

HGNC name	ATP-binding cassette, sub-family A (ABC1), member 4
HGNC id	34

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ARMD2 age related macular degeneration 2 CORD3 retinal cone-rod dystrophy 3 RP19 retinitis pigmentosa 19 STGD1 Stargardt disease 1
Location	1p22.1      Physical location : 94.458.395 - 94.586.705
Synonym name	Rim protein
	ATP-binding transporter retina specific
	retinal-specific ATP-binding cassette transporter
	Stargardt disease protein
	photoreceptor rim protein
Synonym symbol(s)	ABC10, ABCR, ARMD2, CORD3, DKFZp781N1972, FFM, FLJ17534, RMP, RP19, STGD, STGD1

DNA

TYPE	functioning gene
STRUCTURE	128.31 kb     50 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	tel - D1S2849 - D1S2779 - ABCA4 - D1S236 - D1S2775 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000350 50 - 7326 NP_000341 250 2273 fovea and peripheral cone and rod photoreceptors 1998 9666097

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Visual eye retina macula

cells

System Cell Pubmed Species Stage Rna symbol Visual cone photoreceptor Visual rod photoreceptor

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two nucleotide-binding domains (NBDs) and the nucleotide binding fold (NBF), each containing highly conserved Walker motifs, NDB1,(aa 854–1375), NBD2(aa 1898–2273)
	a membrane spanning segment
	two large extracellular/lumen domains (ECD1, aa 62–646; and ECD2, aa 1395–1680)
	a multi-spanning membrane domain
	the EEA-like domain is denoted on the transmembrane helix as EAA
	a conserved VFVNFA motif in C terminal domain which is crucial for a functionally active protein

conjugated

GlycoP

HOMOLOGY

interspecies	ortholog to Abca4, Mus musculus
	homolog to LOC558793, Danio rerio
	ortholog to Abca4, rattus norvegicus
	ortholog to ABCA4, Pan troglodytes

Homologene

FAMILY

ABCA subfamily of ATP binding cassette transporters

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION	plasma membrane
text	localized to the rim of rod phosphoreceptor outer segment discs (RMP protein)

basic FUNCTION	mediates transport of essential molecules across the photoreceptor cell membrane: transport of the Schiff base adduct of all-trans-retinal and phosphatidylethanolamine
	(PE)3 known as N-retinylidene-PE or N-ret-PE across disc membranes as part of visual cycle
	implicated in the transport of retinoid compounds across the outer segment disk membrane following the photoactivation of rhodopsin
	implicated in the removal of retinal derivatives from outer segments following photoexcitation
	the VFVNFA motif in the c-terminal domain of ABCA4 plays a crucial role in proper folding of the protein into a functionally active conformation
	ATP-binding cassette transporter coupling ATP hydrolysis to the translocation of a visual cycle intermediate (N-retinylidene-phosphatidylethanolamine—N-ret-PE) from the inner leaflet of the photoreceptor disk membrane to the outer leaflet
	is a novel importer that actively flips N-retinylidene-phosphatidylethanolamine from the lumen to the cytoplasmic leaflet of disc membranes, thereby facilitating the removal of potentially toxic retinoid compounds from photoreceptors
	is an essential component of the visual transduction cycle of vertebrate retina
	role of ABCA4 in 11-cis-retinal translocation
	transports N-retinylidene-phosphatidylethanolamine to the outer side of disc membranes to prevent formation of toxic compounds causing macular degeneration
	role of the ATP-binding cassette transporter ABCA4 associated with Stargardt macular degeneration and retinol dehydrogenases (RDH) in the clearance of all-trans-retinal from photoreceptors following photoexcitation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

active transport , cellular trafficking transport

text	small molecule transport across the photoreceptor cell membrane

PATHWAY

metabolism

signaling

sensory transduction/vision

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP binding

protein

glutamic acid-rich proteins (GARPs), ABCA1(Körschen et al, 1999)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

RP19 , STGD1 , CORD3 , ARMD2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional         initial implication in age-related macular degeneration was not confirmed (Lotery,07)

Susceptibility

to age related macular degeneration in families of STGD1

Variant & Polymorphism

Candidate gene
Marker
Therapy target	Isotretinoin blocks the formation of A2E biochemically and the accumulation of lipofuscin pigments. Isotretinoin might delay the onset of visual loss in patients with Stargardt disease

ANIMAL & CELL MODELS

Abcr-/- mice showed delayed dark adaptation, increased all-trans-retinaldehyde , elevated phosphatidylethanolamine in outer segments, accumulation of the protonated Schiff base complex of all-trans-RAL and PE, and striking deposition of a major lipofuscin fluorophore in retinal pigment epithelium (Radu et a, 2003)