UniProtKB/SwissProt variant VAR

Krueppel-like factor 1
Gene: KLF1
Feedback?

Variant information Variant position:

325 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Glutamate (E) to Lysine (K) at position 325 (E325K, p.Glu325Lys). 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 medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 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:

In CDAN4A; pathogenic; has a dominant-negative effect on the transcriptional activation of CD44 and AQP1 promoters; the orthologous mouse mutation alters DNA-binding specificity resulting in ectopic transcription of non-erythroid genes. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs267607201 [ dbSNP | Ensembl ]

Sequence information Variant position:

325 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

362 The length of the canonical sequence.
Location on the sequence:

GEKPYACTWEGCGWRFARSD E LTRHYRKHTGQRPFRCQLCP 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                         GEKPYACTW---EGCGWRFARSDELTRHY---------RKHTG-QRPFR------------------CQL-------CP

Mouse                         GEKPYACSW---DGCDWRFARSDELTRHY---------RKH

Zebrafish                     GEKPYHCTW---DGCGWKFARSDELTRHF---------RKH

Caenorhabditis elegans        GEKPYECSW---DGCDWRFARSDELTRHY---------RKH

Fission yeast                 STSRYVSAWLASDDSEVSIKHAVDMVEAFLGGDMEYDVQNE

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.

Type	Positions	Description
Chain	1 – 362	Krueppel-like factor 1
Zinc finger	309 – 333	C2H2-type 2

Literature citations
A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia.
Arnaud L.; Saison C.; Helias V.; Lucien N.; Steschenko D.; Giarratana M.C.; Prehu C.; Foliguet B.; Montout L.; de Brevern A.G.; Francina A.; Ripoche P.; Fenneteau O.; Da Costa L.; Peyrard T.; Coghlan G.; Illum N.; Birgens H.; Tamary H.; Iolascon A.; Delaunay J.; Tchernia G.; Cartron J.P.;
Am. J. Hum. Genet. 87:721-727(2010)
Cited for: VARIANT PRO-102; VARIANT CDAN4A LYS-325; CHARACTERIZATION OF VARIANT CDAN4A LYS-325; INVOLVEMENT IN CDAN4A; ROLE IN ERYTHROPOIESIS; FUNCTION AS TRANSCRIPTIONAL ACTIVATOR OF CD44 AND AQP1; SUBCELLULAR LOCATION; Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin: review of all reported cases and development of a clinical diagnostic paradigm.
Jaffray J.A.; Mitchell W.B.; Gnanapragasam M.N.; Seshan S.V.; Guo X.; Westhoff C.M.; Bieker J.J.; Manwani D.;
Blood Cells Mol. Dis. 51:71-75(2013)
Cited for: VARIANT CDAN4A LYS-325; A Case of Congenital Dyserythropoeitic Anemia Type IV Caused by E325K Mutation in Erythroid Transcription Factor KLF1.
Ortolano R.; Forouhar M.; Warwick A.; Harper D.;
J. Pediatr. Hematol. Oncol. 40:e389-e391(2018)
Cited for: VARIANT CDAN4A LYS-325; KLF1 E325K-associated Congenital Dyserythropoietic Anemia Type IV: Insights Into the Variable Clinical Severity.
Ravindranath Y.; Johnson R.M.; Goyette G.; Buck S.; Gadgeel M.; Gallagher P.G.;
J. Pediatr. Hematol. Oncol. 40:e405-e409(2018)
Cited for: VARIANT CDAN4A LYS-325; Corrupted DNA-binding specificity and ectopic transcription underpin dominant neomorphic mutations in KLF/SP transcription factors.
Ilsley M.D.; Huang S.; Magor G.W.; Landsberg M.J.; Gillinder K.R.; Perkins A.C.;
BMC Genomics 20:417-417(2019)
Cited for: CHARACTERIZATION OF VARIANT CDAN4A LYS-325; A Krueppel-like factor 1 (KLF1) Mutation Associated with Severe Congenital Dyserythropoietic Anemia Alters Its DNA-Binding Specificity.
Kulczynska K.; Bieker J.J.; Siatecka M.;
Mol. Cell. Biol. 40:0-0(2020)
Cited for: CHARACTERIZATION OF VARIANT CDAN4A LYS-325;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13351: Variant p.Glu325Lys