ABCD4 (ATP binding cassette subfamily D member 4)

Gene

• Entrez ID: 5826
• Gene name: ATP binding cassette subfamily D member 4
• Gene symbol: ABCD4
• Synonyms: ABC41, EST352188, MAHCJ, P70R, P79R, PMP69, PXMP1L
• Chromosome: 14
• Chromosome location: 14q24.3
• Summary: The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ALD subfamily, which is involved in peroxisomal import of fatty acids and/or fatty acyl-CoAs in the organelle. All known peroxisomal ABC transporters are half transporters which require a partner half transporter molecule to form a functional homodimeric or heterodimeric transporter. The function of this peroxisomal membrane protein is unknown. However, it is speculated that it may function as a heterodimer for another peroxisomal ABC transporter and, therefore, may modify the adrenoleukodystrophy phenotype. It may also play a role in the process of peroxisome biogenesis. Alternative splicing results in several protein-coding and non-protein-coding variants. [provided by RefSeq, Jul 2017]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs45568335	G>A	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, intron variant, coding sequence variant, missense variant
rs141868117	G>A	Conflicting-interpretations-of-pathogenicity	Missense variant, intron variant, coding sequence variant, non coding transcript variant
rs201777056	T>C,G	Not-provided, pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs387907315	->GA	Pathogenic	Coding sequence variant, genic downstream transcript variant, frameshift variant, non coding transcript variant, 3 prime UTR variant
rs767795583	G>A	Pathogenic	Genic downstream transcript variant, stop gained, non coding transcript variant, synonymous variant, coding sequence variant
rs769364566	C>A,T	Pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030267	hsa-miR-26b-5p	Microarray	19088304
MIRT042098	hsa-miR-484	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005324	Function	Long-chain fatty acid transporter activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	25535791
GO:0005524	Function	ATP binding	IBA	21873635
GO:0005524	Function	ATP binding	NAS	9266848
GO:0005765	Component	Lysosomal membrane	IDA	27456980
GO:0005765	Component	Lysosomal membrane	TAS
GO:0005777	Component	Peroxisome	IDA	9302272, 14533738
GO:0005777	Component	Peroxisome	IDA	19010322, 27456980
GO:0005778	Component	Peroxisomal membrane	IBA	21873635
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	27456980
GO:0006635	Process	Fatty acid beta-oxidation	IBA	21873635
GO:0007031	Process	Peroxisome organization	IBA	21873635
GO:0009235	Process	Cobalamin metabolic process	IMP	22922874
GO:0009235	Process	Cobalamin metabolic process	TAS
GO:0015910	Process	Long-chain fatty acid import into peroxisome	IBA	21873635
GO:0016021	Component	Integral component of membrane	NAS	9266848
GO:0016887	Function	ATPase activity	IBA	21873635
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IBA	21873635
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	NAS	9266848
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	TAS
GO:0042760	Process	Very long-chain fatty acid catabolic process	IBA	21873635
GO:0043190	Component	ATP-binding cassette (ABC) transporter complex	NAS	9266848
GO:0055085	Process	Transmembrane transport	NAS	9266848
GO:1990830	Process	Cellular response to leukemia inhibitory factor	IEA

Other IDs

• MIM: 603214
• HGNC: 68
• e!Ensembl: ENSG00000119688

Protein

• UniProt ID: O14678
• Protein name: Lysosomal cobalamin transporter ABCD4 (ATP-binding cassette sub-family D member 4) (PMP70-related protein) (P70R) (Peroxisomal membrane protein 1-like) (PXMP1-L) (Peroxisomal membrane protein 69) (PMP69)
• Protein function: Lysosomal transporter that plays a role in the lysosomal release of vitamin B12 into the cytosol (PubMed:22922874). Targeted by LMBRD1 lysosomal chaperone from the endoplasmic reticulum to the lysosomal membrane (PubMed:27456980). Then forms a complex with lysosomal chaperone LMBRD1 and cytosolic MMACHC to transport cobalamin across the lysosomal membrane (PubMed:25535791).
• PDB: 6JBJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF06472	ABC_membrane_2	27 → 294	ABC transporter transmembrane region 2	Family
  PF00005	ABC_tran	404 → 552	ABC transporter	Domain

• Sequence:

  MAVAGPAPGAGARPRLDLQFLQRFLQILKVLFPSWSSQNALMFLTLLCLTLLEQFVIYQV
  GLIPSQYYGVLGNKDLEGFKTLTFLAVMLIVLNSTLKSFDQFTCNLLYVSWRKDLTEHLH
  RLYFRGRAYYTLNVLRDDIDNPDQRISQDVERFCRQLSSMASKLIISPFTLVYYTYQCFQ
  STGWLGPVSIFGYFILGTVVNKTLMGPIVMKLVHQEKLEGDFRFKHMQIRVNAEPAAFYR
  AGHVEHMRTDRRLQRLLQTQRELMSKELWLYIGINTFDYLGSILSYVVIAIPIFSGVYGD
  LSPAELSTLVSKNAFVCIYLISCFTQLIDLSTTLSDVAGYTHRIGQLRETLLDMSLKSQD
  CEILGESEWGLDTPPGWPAAEPADTAFLLERVSISAPSSDKPLIKDLSLKISEGQSLLIT
  GNTGTGKTSLLRVLGGLWTSTRGSVQMLTDFGPHGVLFLPQKPFFTDGTLREQVIYPLKE
  VYPDSGSADDERILRFLELAGLSNLVARTEGLDQQVDWNWYDVLSPGEMQRLSFARLFYL
  QPKYAVLDEATSALTEEVESELYRIGQQLGMTFISVGHRQSLEKFHSLVLKLCGGGRWEL
  MRIKVE

• Sequence length: 606