ABCA4

Protein identityUniProt · HPA

UniProt accession

P78363

Gene

ABCA4

Ensembl

ENSG00000198691

Chromosome

1

Canonical length

2273 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted membrane proteins, Transporters

Subcellular location

Endoplasmic reticulum

OverviewNCBI Gene

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This protein is a retina-specific ABC transporter with N-retinylidene-PE as a substrate. It is expressed exclusively in retina photoreceptor cells, and the gene product mediates transport of an essental molecule, all-trans-retinal aldehyde (atRAL), across the photoreceptor cell membrane. Mutations in this gene are found in patients diagnosed with Stargardt disease, a form of juvenile-onset macular degeneration. Mutations in this gene are also associated with retinitis pigmentosa-19, cone-rod dystrophy type 3, early-onset severe retinal dystrophy, fundus flavimaculatus, and macular degeneration age-related 2. [provided by RefSeq, Sep 2019]

Canonical amino-acid sequenceUniProt

2273 residues, UniProt reviewed canonical sequence.

>P78363|ABCA4
     1  MGFVRQIQLL LWKNWTLRKR QKIRFVVELV WPLSLFLVLI WLRNANPLYS HHECHFPNKA
    61  MPSAGMLPWL QGIFCNVNNP CFQSPTPGES PGIVSNYNNS ILARVYRDFQ ELLMNAPESQ
   121  HLGRIWTELH ILSQFMDTLR THPERIAGRG IRIRDILKDE ETLTLFLIKN IGLSDSVVYL
   181  LINSQVRPEQ FAHGVPDLAL KDIACSEALL ERFIIFSQRR GAKTVRYALC SLSQGTLQWI
   241  EDTLYANVDF FKLFRVLPTL LDSRSQGINL RSWGGILSDM SPRIQEFIHR PSMQDLLWVT
   301  RPLMQNGGPE TFTKLMGILS DLLCGYPEGG GSRVLSFNWY EDNNYKAFLG IDSTRKDPIY
   361  SYDRRTTSFC NALIQSLESN PLTKIAWRAA KPLLMGKILY TPDSPAARRI LKNANSTFEE
   421  LEHVRKLVKA WEEVGPQIWY FFDNSTQMNM IRDTLGNPTV KDFLNRQLGE EGITAEAILN
   481  FLYKGPRESQ ADDMANFDWR DIFNITDRTL RLVNQYLECL VLDKFESYND ETQLTQRALS
   541  LLEENMFWAG VVFPDMYPWT SSLPPHVKYK IRMDIDVVEK TNKIKDRYWD SGPRADPVED
   601  FRYIWGGFAY LQDMVEQGIT RSQVQAEAPV GIYLQQMPYP CFVDDSFMII LNRCFPIFMV
   661  LAWIYSVSMT VKSIVLEKEL RLKETLKNQG VSNAVIWCTW FLDSFSIMSM SIFLLTIFIM
   721  HGRILHYSDP FILFLFLLAF STATIMLCFL LSTFFSKASL AAACSGVIYF TLYLPHILCF
   781  AWQDRMTAEL KKAVSLLSPV AFGFGTEYLV RFEEQGLGLQ WSNIGNSPTE GDEFSFLLSM
   841  QMMLLDAAVY GLLAWYLDQV FPGDYGTPLP WYFLLQESYW LGGEGCSTRE ERALEKTEPL
   901  TEETEDPEHP EGIHDSFFER EHPGWVPGVC VKNLVKIFEP CGRPAVDRLN ITFYENQITA
   961  FLGHNGAGKT TTLSILTGLL PPTSGTVLVG GRDIETSLDA VRQSLGMCPQ HNILFHHLTV
  1021  AEHMLFYAQL KGKSQEEAQL EMEAMLEDTG LHHKRNEEAQ DLSGGMQRKL SVAIAFVGDA
  1081  KVVILDEPTS GVDPYSRRSI WDLLLKYRSG RTIIMSTHHM DEADLLGDRI AIIAQGRLYC
  1141  SGTPLFLKNC FGTGLYLTLV RKMKNIQSQR KGSEGTCSCS SKGFSTTCPA HVDDLTPEQV
  1201  LDGDVNELMD VVLHHVPEAK LVECIGQELI FLLPNKNFKH RAYASLFREL EETLADLGLS
  1261  SFGISDTPLE EIFLKVTEDS DSGPLFAGGA QQKRENVNPR HPCLGPREKA GQTPQDSNVC
  1321  SPGAPAAHPE GQPPPEPECP GPQLNTGTQL VLQHVQALLV KRFQHTIRSH KDFLAQIVLP
  1381  ATFVFLALML SIVIPPFGEY PALTLHPWIY GQQYTFFSMD EPGSEQFTVL ADVLLNKPGF
  1441  GNRCLKEGWL PEYPCGNSTP WKTPSVSPNI TQLFQKQKWT QVNPSPSCRC STREKLTMLP
  1501  ECPEGAGGLP PPQRTQRSTE ILQDLTDRNI SDFLVKTYPA LIRSSLKSKF WVNEQRYGGI
  1561  SIGGKLPVVP ITGEALVGFL SDLGRIMNVS GGPITREASK EIPDFLKHLE TEDNIKVWFN
  1621  NKGWHALVSF LNVAHNAILR ASLPKDRSPE EYGITVISQP LNLTKEQLSE ITVLTTSVDA
  1681  VVAICVIFSM SFVPASFVLY LIQERVNKSK HLQFISGVSP TTYWVTNFLW DIMNYSVSAG
  1741  LVVGIFIGFQ KKAYTSPENL PALVALLLLY GWAVIPMMYP ASFLFDVPST AYVALSCANL
  1801  FIGINSSAIT FILELFENNR TLLRFNAVLR KLLIVFPHFC LGRGLIDLAL SQAVTDVYAR
  1861  FGEEHSANPF HWDLIGKNLF AMVVEGVVYF LLTLLVQRHF FLSQWIAEPT KEPIVDEDDD
  1921  VAEERQRIIT GGNKTDILRL HELTKIYPGT SSPAVDRLCV GVRPGECFGL LGVNGAGKTT
  1981  TFKMLTGDTT VTSGDATVAG KSILTNISEV HQNMGYCPQF DAIDELLTGR EHLYLYARLR
  2041  GVPAEEIEKV ANWSIKSLGL TVYADCLAGT YSGGNKRKLS TAIALIGCPP LVLLDEPTTG
  2101  MDPQARRMLW NVIVSIIREG RAVVLTSHSM EECEALCTRL AIMVKGAFRC MGTIQHLKSK
  2161  FGDGYIVTMK IKSPKDDLLP DLNPVEQFFQ GNFPGSVQRE RHYNMLQFQV SSSSLARIFQ
  2221  LLLSHKDSLL IEEYSVTQTT LDQVFVNFAK QQTESHDLPL HPRAAGASRQ AQD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ABCA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

12

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

329 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ABCA4.

Disease | AllUniProt

Conditions ABCA4 is implicated in, by any mechanism.

• Stargardt disease 1 (STGD1) MIM:248200
• Fundus flavimaculatus (FFM) MIM:248200
• Macular degeneration, age-related, 2 (ARMD2) MIM:153800
• Cone-rod dystrophy 3 (CORD3) MIM:604116
• Retinitis pigmentosa 19 (RP19) MIM:601718

Disease | GeneticClinVar

1,471 pathogenic / likely-pathogenic of 4,582 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Severe early-childhood-onset retinal dystrophy
• Retinal dystrophy
• Retinitis pigmentosa 19
• Cone-rod dystrophy 3
• Age related macular degeneration 2

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.91

gnomAD pLI

0

gnomAD missense Z

-0.66

DepMap mean gene effect

-0.22

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• lipid transport
• phospholipid transfer to membrane
• phospholipid translocation
• photoreceptor cell maintenance
• phototransduction, visible light
• retinal metabolic process
• retinoid metabolic process
• transmembrane transport
• visual perception

Molecular functions

• 11-cis retinal binding
• ABC-type transporter activity
• all-trans retinal binding
• ATP binding
• ATP hydrolysis activity
• ATPase-coupled intramembrane lipid transporter activity
• ATPase-coupled transmembrane transporter activity
• GTPase activity
• phosphatidylethanolamine flippase activity
• phospholipid transporter activity
• retinoid binding
• retinol transmembrane transporter activity
• flippase activity
• N-retinylidene-phosphatidylethanolamine flippase activity

Cellular components

• cytoplasmic vesicle
• endoplasmic reticulum
• membrane
• photoreceptor disc membrane
• photoreceptor outer segment
• plasma membrane
• rod photoreceptor disc membrane

Protein domainsUniProt · Pfam · InterPro

• ABC transporter-like, ATP-binding domain
• AAA+ ATPase domain
• ABC-2 type transporter, transmembrane domain
• ABC transporter-like, conserved site
• ABC transporter A
• P-loop containing nucleoside triphosphate hydrolase
• ABCA1-4-like, C-terminal R2 regulatory domain
• ABC transporter
• ABC-2 family transporter protein
• ABCA1-like, C-terminal R1 regulatory domain
• Retinal-specific ATP-binding cassette transporter

KeywordsUniProt

• Age-related macular degeneration
• ATP-binding
• Cell projection
• Cone-rod dystrophy
• Cytoplasmic vesicle
• Disulfide bond
• Endoplasmic reticulum
• Glycoprotein
• Hydrolase
• Membrane
• Nucleotide-binding
• Phosphoprotein
• Repeat
• Retinitis pigmentosa
• Sensory transduction
• Stargardt disease
• Translocase
• Transmembrane
• Transmembrane helix
• Transport
• Vision