UniProtKB/Swiss-Prot O60706: Variant p.Ala478Val

ATP-binding cassette sub-family C member 9
Gene: ABCC9
Chromosomal location: 12p12.1
Variant information

Variant position:  478
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Alanine (A) to Valine (V) at position 478 (A478V, p.Ala478Val).
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:  Change from small size and hydrophobic (A) to medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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

Involvement in disease:  Hypertrichotic osteochondrodysplasia (HTOCD) [MIM:239850]: A rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. The hypertrichosis leads to thick scalp hair, which extends onto the forehead, and a general increase in body hair. In addition, macrocephaly and coarse facial features, including a broad nasal bridge, epicanthal folds, a wide mouth, and full lips, can be suggestive of a storage disorder. About half of affected individuals are macrosomic and edematous at birth, whereas in childhood they usually have a muscular appearance with little subcutaneous fat. Thickened calvarium, narrow thorax, wide ribs, flattened or ovoid vertebral bodies, coxa valga, osteopenia, enlarged medullary canals, and metaphyseal widening of long bones have been reported. Cardiac manifestations such as patent ductus arteriosus, ventricular hypertrophy, pulmonary hypertension, and pericardial effusions are present in approximately 80% of cases. Motor development is usually delayed due to hypotonia. Most patients have a mild speech delay, and a small percentage have learning difficulties or intellectual disability. {ECO:0000269|PubMed:22608503, ECO:0000269|PubMed:22610116}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HTOCD.
Any additional useful information about the variant.



Sequence information

Variant position:  478
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1549
The length of the canonical sequence.

Location on the sequence:   VGAAVIVLLAPIQYFIATKL  A EAQKSTLDYSTERLKKTNEI
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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         VGAAVIVLLAPIQYFIATKLAEAQKSTLDYSTERLKKTNEI

Mouse                         VGAAVIVLLAPIQYFIATKLAEAQKSTLDYSTERLKKTNEI

Rat                           VGAAVIVLLAPIQYFIATKLAEAQKSTLDYSTERLKKTNEI

Rabbit                        VGAAVIVLLAPMQYFIATKLAEAQKSTLDYSTERLKKTNEI

Slime mold                    VGTAVILISFPINSYFGKKTSDYYEKLLKYTDKRVSTTSEF

Sequence annotation in neighborhood:  
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 – 1549 ATP-binding cassette sub-family C member 9
Topological domain 477 – 531 Cytoplasmic
Domain 297 – 597 ABC transmembrane type-1 1


Literature citations

Cantu syndrome is caused by mutations in ABCC9.
van Bon B.W.; Gilissen C.; Grange D.K.; Hennekam R.C.; Kayserili H.; Engels H.; Reutter H.; Ostergaard J.R.; Morava E.; Tsiakas K.; Isidor B.; Le Merrer M.; Eser M.; Wieskamp N.; de Vries P.; Steehouwer M.; Veltman J.A.; Robertson S.P.; Brunner H.G.; de Vries B.B.; Hoischen A.;
Am. J. Hum. Genet. 90:1094-1101(2012)
Cited for: VARIANTS HTOCD VAL-478; TYR-1043; GLN-1154 AND TRP-1154;

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.