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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14678: Variant p.Tyr319Cys

Lysosomal cobalamin transporter ABCD4
Gene: ABCD4
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Variant information Variant position: help 319 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Tyrosine (Y) to Cysteine (C) at position 319 (Y319C, p.Tyr319Cys). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from large size and aromatic (Y) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In MAHCJ; strong decrease of ATPase activity. Strong decrease of cobalamin transport activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 319 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 606 The length of the canonical sequence.
Location on the sequence: help GDLSPAELSTLVSKNAFVCI Y LISCFTQLIDLSTTLSDVAG The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         GDLSPAELSTLVSKNAFVCIYLISCFTQLIDLSTTLSDVAG

Mouse                         GDLSPTELSTLVSKNAFVCIYLISCFTQLIDLSTTLSDVAG
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 606 Lysosomal cobalamin transporter ABCD4
Transmembrane 314 – 334 Helical
Domain 39 – 332 ABC transmembrane type-1
Mutagenesis 319 – 319 Y -> A. Decreases of ATPase activity. Decreases cobalamin transport activity.
Mutagenesis 319 – 319 Y -> F. Does not affect ATPase activity. Does not affect cobalamin transport activity.



Literature citations
Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism.
Coelho D.; Kim J.C.; Miousse I.R.; Fung S.; du Moulin M.; Buers I.; Suormala T.; Burda P.; Frapolli M.; Stucki M.; Nurnberg P.; Thiele H.; Robenek H.; Hohne W.; Longo N.; Pasquali M.; Mengel E.; Watkins D.; Shoubridge E.A.; Majewski J.; Rosenblatt D.S.; Fowler B.; Rutsch F.; Baumgartner M.R.;
Nat. Genet. 44:1152-1155(2012)
Cited for: FUNCTION; VARIANT MAHCJ CYS-319; INVOLVEMENT IN MAHCJ; MUTAGENESIS OF LYS-427; ASP-548 AND GLU-549; SUBCELLULAR LOCATION; The lysosomal protein ABCD4 can transport vitamin B12 across liposomal membranes in vitro.
Kitai K.; Kawaguchi K.; Tomohiro T.; Morita M.; So T.; Imanaka T.;
J. Biol. Chem. 296:100654-100654(2021)
Cited for: CATALYTIC ACTIVITY; FUNCTION; BIOPHYSICOCHEMICAL PROPERTIES; MUTAGENESIS OF ASN-141; TYR-319 AND LYS-427; SUBCELLULAR LOCATION; INTERACTION WITH LMBRD1; CHARACTERIZATION OF VARIANTS MAHCJ CYS-319 AND ASN-141; SUBUNIT; Cryo-EM structure of human lysosomal cobalamin exporter ABCD4.
Xu D.; Feng Z.; Hou W.T.; Jiang Y.L.; Wang L.; Sun L.; Zhou C.Z.; Chen Y.;
Cell Res. 29:1039-1041(2019)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 2-606; CHARACTERIZATION OF VARIANTS MAHCJ CYS-319 AND GLN-432; MUTAGENESIS OF GLU-549; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.