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UniProtKB/Swiss-Prot Q12946: Variant p.Phe106Leu

Forkhead box protein F1
Gene: FOXF1
Variant information

Variant position:  106
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Phenylalanine (F) to Leucine (L) at position 106 (F106L, p.Phe106Leu).
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:  Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) [MIM:265380]: A rare developmental disorder characterized by abnormal development of the capillary vascular system in the lungs. Histological features include failure of formation and ingrowth of alveolar capillaries, medial muscular thickening of small pulmonary arterioles with muscularization of the intraacinar arterioles, thickened alveolar walls, and anomalously situated pulmonary veins running alongside pulmonary arterioles and sharing the same adventitial sheath. Less common features include a reduced number of alveoli and a patchy distribution of the histopathologic changes. Affected infants present with respiratory distress and the disease is fatal within the newborn period. Additional features include multiple congenital anomalies affecting the cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems, as well as disruption of the normal right-left asymmetry of intrathoracic or intraabdominal organs. ACDMPV is a rare cause of persistent pulmonary hypertension of the newborn, an abnormal physiologic state caused by failure of transition of the pulmonary circulation from the high pulmonary vascular resistance of the fetus to the low pulmonary vascular resistance of the newborn. {ECO:0000269|PubMed:19500772, ECO:0000269|PubMed:23505205, ECO:0000269|PubMed:27145217}. 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 ACDMPV.
Any additional useful information about the variant.



Sequence information

Variant position:  106
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  379
The length of the canonical sequence.

Location on the sequence:   RGSYQGWKNSVRHNLSLNEC  F IKLPKGLGRPGKGHYWTIDP
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                         RGSYQGWKNSVRHNLSLNECFIKLPKGLGRPGKGHYWTIDP

Mouse                         RGAYQGWKNSVRHNLSLNECFIKLPKGLGRPGKGHYWTIDP

Xenopus tropicalis            RGSYQGWKNSVRHNLSLNECFIKLPKGLGRPGKGHYWTIDP

Zebrafish                     RGSYQGWKNSVRHNLSLNECFIKLPKGLGRPGKGHYWTIDP

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 – 379 Forkhead box protein F1
DNA binding 47 – 138 Fork-head


Literature citations

Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain.
Sen P.; Yang Y.; Navarro C.; Silva I.; Szafranski P.; Kolodziejska K.E.; Dharmadhikari A.V.; Mostafa H.; Kozakewich H.; Kearney D.; Cahill J.B.; Whitt M.; Bilic M.; Margraf L.; Charles A.; Goldblatt J.; Gibson K.; Lantz P.E.; Garvin A.J.; Petty J.; Kiblawi Z.; Zuppan C.; McConkie-Rosell A.; McDonald M.T.; Peterson-Carmichael S.L.; Gaede J.T.; Shivanna B.; Schady D.; Friedlich P.S.; Hays S.R.; Palafoll I.V.; Siebers-Renelt U.; Bohring A.; Finn L.S.; Siebert J.R.; Galambos C.; Nguyen L.; Riley M.; Chassaing N.; Vigouroux A.; Rocha G.; Fernandes S.; Brumbaugh J.; Roberts K.; Ho-Ming L.; Lo I.F.; Lam S.; Gerychova R.; Jezova M.; Valaskova I.; Fellmann F.; Afshar K.; Giannoni E.; Muhlethaler V.; Liang J.; Beckmann J.S.; Lioy J.; Deshmukh H.; Srinivasan L.; Swarr D.T.; Sloman M.; Shaw-Smith C.; van Loon R.L.; Hagman C.; Sznajer Y.; Barrea C.; Galant C.; Detaille T.; Wambach J.A.; Cole F.S.; Hamvas A.; Prince L.S.; Diderich K.E.; Brooks A.S.; Verdijk R.M.; Ravindranathan H.; Sugo E.; Mowat D.; Baker M.L.; Langston C.; Welty S.; Stankiewicz P.;
Hum. Mutat. 34:801-811(2013)
Cited for: VARIANTS ACDMPV GLN-49; SER-49; PHE-52; CYS-53; ASN-74; ILE-85; LEU-85; SER-85; TRP-86; GLU-91; VAL-91; MET-96; HIS-97; GLN-98; LEU-101; LEU-106; 113-LEU--GLY-119 DEL; ASP-119; LEU-126; LEU-139 AND TRP-330;

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.