UniProtKB/Swiss-Prot Q14683: Variant p.Phe1122Leu

Structural maintenance of chromosomes protein 1A
Gene: SMC1A
Chromosomal location: Xp11.21-p11.22
Variant information

Variant position:  1122
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 1122 (F1122L, p.Phe1122Leu).
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:  Cornelia de Lange syndrome 2 (CDLS2) [MIM:300590]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269|PubMed:16604071, ECO:0000269|PubMed:17221863, ECO:0000269|PubMed:17273969, ECO:0000269|PubMed:19701948, ECO:0000269|PubMed:20358602, ECO:0000269|PubMed:20635401}. 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 CDLS2.
Any additional useful information about the variant.



Sequence information

Variant position:  1122
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1233
The length of the canonical sequence.

Location on the sequence:   NPEEPYLDGINYNCVAPGKR  F RPMDNLSGGEKTVAALALLF
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                         NPEEPYLDGINYNCVAPGKRFRPMDNLSGGEKTVAALALLF

Mouse                         NPEEPYLDGINYNCVAPGKRFRPMDNLSGGEKTVAALALLF

Rat                           NPEEPYLDGINYNCVAPGKRFRPMDNLSGGEKTVAALALLF

Bovine                        NPEEPYLDGINYNCVAPGKRFRPMDNLSGGEKTVAALALLF

Xenopus laevis                NPEEPYLDGINYNCVAPGKRFRPMDNLSGGEKTVAALALLF

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 – 1233 Structural maintenance of chromosomes protein 1A


Literature citations

Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of Cornelia de Lange syndrome with predominant mental retardation.
Deardorff M.A.; Kaur M.; Yaeger D.; Rampuria A.; Korolev S.; Pie J.; Gil-Rodriguez C.; Arnedo M.; Loeys B.; Kline A.D.; Wilson M.; Lillquist K.; Siu V.; Ramos F.J.; Musio A.; Jackson L.S.; Dorsett D.; Krantz I.D.;
Am. J. Hum. Genet. 80:485-494(2007)
Cited for: VARIANTS CDLS2 58-VAL--ARG-62 DEL; VAL-133; HIS-196; CYS-496; HIS-496; TRP-711; GLN-790 AND LEU-1122;

SMC1A expression and mechanism of pathogenicity in probands with X-Linked Cornelia de Lange syndrome.
Liu J.; Feldman R.; Zhang Z.; Deardorff M.A.; Haverfield E.V.; Kaur M.; Li J.R.; Clark D.; Kline A.D.; Waggoner D.J.; Das S.; Jackson L.G.; Krantz I.D.;
Hum. Mutat. 30:1535-1542(2009)
Cited for: VARIANTS CDLS2 58-VAL--ARG-62 DEL; VAL-133; LYS-141; HIS-196; LYS-268 DEL; SER-306 DEL; GLN-398; CYS-496; HIS-496; GLU-683 DEL; GLY-693; TRP-711; PHE-781; GLN-790; GLY-816; GLN-1049; LEU-1122 AND TRP-1123;

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.