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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q96QS3: Variant p.Leu343Gln

Homeobox protein ARX
Gene: ARX
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Variant information Variant position: help 343 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Leucine (L) to Glutamine (Q) at position 343 (L343Q, p.Leu343Gln). 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: help Change from medium size and hydrophobic (L) to medium size and polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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: help In LISX2; abolishes transcriptional activation of KDM5C; abolishes sequence-specific DNA-binding; reduces transcriptional repression of LMO1 and SHOX2. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 343 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 562 The length of the canonical sequence.
Location on the sequence: help LLKRKQRRYRTTFTSYQLEE L ERAFQKTHYPDVFTREELAM 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         LLKRKQRRYRTTFTSYQLEELERAFQKTHYPDVFTREELAM

Mouse                         LLKRKQRRYRTTFTSYQLEELERAFQKTHYPDVFTREELAM

Rat                           LLKRKQRRYRTTFTSYQLEELERAFQKTHYPDVFTREELAM

Zebrafish                     MLKRKQRRYRTTFTSYQLEELERAFQKTHYPDVFTREELAM
Sequence annotation in neighborhood: help 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 – 562 Homeobox protein ARX
DNA binding 328 – 387 Homeobox
Mutagenesis 358 – 358 R -> S. Abolishes sequence-specific DNA-binding; reduces transcriptional repression of LMO1 and SHOX2. Abolishes transcriptional activation of KDM5C.



Literature citations
Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans.
Kitamura K.; Yanazawa M.; Sugiyama N.; Miura H.; Iizuka-Kogo A.; Kusaka M.; Omichi K.; Suzuki R.; Kato-Fukui Y.; Kamiirisa K.; Matsuo M.; Kamijo S.; Kasahara M.; Yoshioka H.; Ogata T.; Fukuda T.; Kondo I.; Kato M.; Dobyns W.B.; Yokoyama M.; Morohashi K.;
Nat. Genet. 32:359-369(2002)
Cited for: FUNCTION; VARIANTS LISX2 HIS-332 AND GLN-343; Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation.
Kato M.; Das S.; Petras K.; Kitamura K.; Morohashi K.; Abuelo D.N.; Barr M.; Bonneau D.; Brady A.F.; Carpenter N.J.; Cipero K.L.; Frisone F.; Fukuda T.; Guerrini R.; Iida E.; Itoh M.; Lewanda A.F.; Nanba Y.; Oka A.; Proud V.K.; Saugier-Veber P.; Schelley S.L.; Selicorni A.; Shaner R.; Silengo M.; Stewart F.; Sugiyama N.; Toyama J.; Toutain A.; Vargas A.L.; Yanazawa M.; Zackai E.H.; Dobyns W.B.;
Hum. Mutat. 23:147-159(2004)
Cited for: FUNCTION; VARIANTS LISX2 PRO-332; HIS-332; GLN-343; ARG-353 AND THR-521; VARIANT ACCAG ASN-333; ARX homeodomain mutations abolish DNA binding and lead to a loss of transcriptional repression.
Shoubridge C.; Tan M.H.; Seiboth G.; Gecz J.;
Hum. Mol. Genet. 21:1639-1647(2012)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT ACCAG ASN-333; CHARACTERIZATION OF VARIANT DEE1 LEU-353; CHARACTERIZATION OF VARIANTS LISX2 PRO-332; GLN-343 AND ARG-353; MUTAGENESIS OF ARG-358 AND ARG-379; Histone demethylase KDM5C is a SAHA-sensitive central hub at the crossroads of transcriptional axes involved in multiple neurodevelopmental disorders.
Poeta L.; Padula A.; Attianese B.; Valentino M.; Verrillo L.; Filosa S.; Shoubridge C.; Barra A.; Schwartz C.E.; Christensen J.; van Bokhoven H.; Helin K.; Lioi M.B.; Collombat P.; Gecz J.; Altucci L.; Di Schiavi E.; Miano M.G.;
Hum. Mol. Genet. 28:4089-4102(2019)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS LISX2 PRO-332; GLN-343 AND ARG-353; CHARACTERIZATION OF VARIANT ACCAG ASN-333; MUTAGENESIS OF ARG-358 AND ARG-379;
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.