UniProtKB/Swiss-Prot P48436: Variant p.Phe112Leu

Transcription factor SOX-9
Gene: SOX9
Chromosomal location: 17q24.1-q25.3
Variant information

Variant position:  112
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 Phenylalanine (F) to Leucine (L) at position 112 (F112L, p.Phe112Leu).
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 large size and aromatic (F) to medium size and hydrophobic (L)
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:  Campomelic dysplasia (CMD1) [MIM:114290]: Rare, often lethal, dominantly inherited, congenital osteochondrodysplasia, associated with male-to-female autosomal sex reversal in two-thirds of the affected karyotypic males. A disease of the newborn characterized by congenital bowing and angulation of long bones, unusually small scapulae, deformed pelvis and spine and a missing pair of ribs. Craniofacial defects such as cleft palate, micrognathia, flat face and hypertelorism are common. Various defects of the ear are often evident, affecting the cochlea, malleus incus, stapes and tympanum. Most patients die soon after birth due to respiratory distress which has been attributed to hypoplasia of the tracheobronchial cartilage and small thoracic cage. 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 CMD1; loss of DNA binding.
Any additional useful information about the variant.



Sequence information

Variant position:  112
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  509
The length of the canonical sequence.

Location on the sequence:   PVRVNGSSKNKPHVKRPMNA  F MVWAQAARRKLADQYPHLHN
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                         PVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLADQYPHLHN

Rhesus macaque                PVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLADQYPHLHN

Chimpanzee                    PVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLGDQYPHLHN

Mouse                         PVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLADQYPHLHN

Pig                           PVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLADQYPHLHN

Dog                           PVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLADQYPHLHN

Chicken                       PVRVNGSSKNKPHVKRPMNAFMVWAQAARRKLADQYPHLHN

Xenopus tropicalis            PVRVNGSSKSKPHVKRPMNAFMVWAQAARRKLADQYPHLHN

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 – 509 Transcription factor SOX-9
DNA binding 105 – 173 HMG box
Helix 111 – 126


Literature citations

Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal.
Kwok C.; Weller P.A.; Guioli S.; Foster J.W.; Mansour S.; Zuffardi O.; Punnett H.H.; Dominguez-Steglich M.A.; Brook J.D.; Young I.D.; Goodfellow P.N.; Schafer A.J.;
Am. J. Hum. Genet. 57:1028-1036(1995)
Cited for: VARIANTS CMD1 LEU-112 AND VAL-119;

Functional and structural studies of wild type SOX9 and mutations causing campomelic dysplasia.
McDowall S.; Argentaro A.; Ranganathan S.; Weller P.; Mertin S.; Mansour S.; Tolmie J.; Harley V.;
J. Biol. Chem. 274:24023-24030(1999)
Cited for: VARIANTS CMD1 LEU-112; VAL-119; TYR-165 AND ARG-170; 3D-STRUCTURE MODELING;

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.