ABCA4 (also know as ABCR) is a subclass of ATP Binding Cassette transmembrane proteins. The gene name is an abbreviation of its description and classification within the ABC gene family, ATP Binding Cassette, subfamily A, member 4. ABCA4 is exclusivly expressed in the retina and is located around the outer segment disk edges of rod and cone photoreceptors. This Protein is responsible for purging N-retinylidene-PE (RN-PE), a potentially toxic byproduct of opsin signaling proteins which are responsible for translating photons of light into electrochemical s
ABCA4 ChromoLocal

Figure1. Location of ABCA4 gene on chromosome 1. (2)

ignals. (1)


The ABCA4 gene is located on chromosome 1p22 with a sequence length of 128Kb.

ABCA4 Protin Structure

Figure 2. Structural features of the ABCA4 transporter. (a) A linear diagram showing the full transporter arranged as two tandem halves. Each half consists of six membrane spanning segments which together make up the transmembrane domain (TMD). A large exocytoplasmic domain (ECD) separates the first membrane spanning segment from the remaining five membrane spanning segments in each half. The nucleotide binding domain (NBD) lies downstream of the multiple membrane spanning segments. (b) Topological model showing the organization of ABCA4 in the membrane. Each ECD contains multiple N-linked oligosaccharide chains (hexagons) exposed to the lumen side of the disc membrane. A six amino acid motif (VFVNFA) is close to the C-terminus. Other ABCA family members have a similar topological organization. (3)

ABCA4 consists of 50 exons that code for a 2273 amino acid protein that has:
  • 2 exocytoplasmic domains (ECD): purpose of these is unknown. In ABCA1 the ECD binds ApoA1
  • 2 nucleoptide binding domains (NBD): Bind ATP for hydrolysis
  • 12 transmembrane segments: A-helicies create the pore between cytoplasm and photoreceptor disc lumen
  • VFVNFA motif: A conserved sequence located at C-terminus of protein. It is thought to play a role in proper proten folding. This motif also occurs in ABCA1.

You can see why this complex protein would have 50 exons!


ABCA4 is responsible for clearing The build up of opsin signaling byproducts, if not cleared by ABCA4, cause a cascade of oxidative events that lead to the accumulation of N-retinyledin-N-retinylethanolamin (A2E). Accumulation of A2E causes another major cascade of events that lead to degeneration of retinal epithelial cells. (3)

Sequencing & Identifying the GeneEdit

ABCR was identified among expressed sequence tags (ESTs) that were obtained from 5,000 retina cDNA clones and vaguely mapped to human chromosome 1p13-p21 region using a whole genome radiation hybrid panel. Searches of the dbESTs database were performed using BLAST on the NCBI file server. For a more detailed location of the gene, yeast artifical chromosomes (YACs) were elongated using

In this northern blot the hybridization primer is complementary to the ABCA4 mRNA; which shows advancement along the gel in the retinal tissue only. This indicates that expression of ABCA4 is retina specific. Tissues samples are in the following order: brain, heart, kidney, liver, lung, retina, spleen. All tissues are from mice. (4)

a primer that supposidly corresponded to the 3' untranslated region of the ABCA4 gene. 12 YACs were identified as containing the 3' end of the ABCA4 gene, which narrowed the location of the gene to be between microsatellite markers D1S3361 & D1S236.

Hybridization of the ABCR probe to a northern blot containing total RNA from rat retina and other tissues showed that the expression of this gene is retina specific.

Several EST's that were derived from retina cDNA libraries and had high similarity to the mouse Abc1 gene were used to assemble most of the ABCR cDNA sequence. The retinal cDNA clones were linked using Reverse Transcription PCR (RT-PCR) and by screening the human retina cDNA library with 3' & 5' PCR probes in conjuction with 5'RACE (Rapid Amplification of cDNA Ends) to find the terminal sequences of the gene.

By screening the bacteriophage lambda human genomic library with cDNA probes a contig was found that contained the whole ABCA4 coding region. Intron and exon structure was determined by direct sequencing of genomic and cDNA clones. (4)

It was determined that the ABCA4 protein was located specifically in the cone and rod photoreceptors. Hybridization signals were identified only on the inner segments of the photoreceptor and not in the retinal pigment epithelium in occular tissue from albine mice. ABCA4 transcripts from humans are very similar to the mouse, so it was assumed that the location of ABCA4 was the same for humans. (4)

Determining Correlation to Stargardt Disease (STGD)Edit

48 STGD families went thought mutational analysis of the ABCA4 gene. 19 different mutations were identified which represented mostly missense mutations in conserved amino acid sequences mosly in the ATP binding domain, but also in the transmembrane proteins. Base pair insertions and deletions were also identified. These mutations were found only in STGD when compared to 40 unrelated normal controls which suggests these genetic alterations represent disease causing mutations.

There were 5 polymorphisms identified that were also found in at least 1 of the 40 disease free control subjects. These polymorphisms are not considered to be linked with the disease. In the study of one family with two unaffected parents and two infected children it was discovered that each parent had a copy of the same mutant allele. Each child had two copies of the mutant allele. This shows that the gene is inherrited in an autosomal recessive manner. (4)

Treatment & Gene TherapyEdit


  1. Wikipedia. ABCA4. Last modified: Aug 27 2012.
  2. Genetics Home Reference. ABCA4. Last Modified: Nov 2010.
  3. R. Molday, et al. The role of the photoreceptor ABC transporter ABCA4 in lipid transport and Stargardt macular degeneration. Biochimica et Biophysica Acta. Vol 1791, Issue 7, pg 573-583. 20 Feb 2009.
  4. Allikmets, Rando, et al. A photoreceptor cell-specific ATP-binding transporteer gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nature Genetics. Vol 15, pg 236-246. Mar 1997.