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UniProtKB/Swiss-Prot Q9H9Q4: Variant p.Cys123Arg

Non-homologous end-joining factor 1
Gene: NHEJ1
Variant information

Variant position:  123
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 Cysteine (C) to Arginine (R) at position 123 (C123R, p.Cys123Arg).
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 polar (C) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 NHEJ1-SCID.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  123
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  299
The length of the canonical sequence.

Location on the sequence:   ALILRVRSELSGLPFYWNFH  C MLASPSLVSQHLIRPLMGMS
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                         ALILRVRSELSGLPFYWNFHCMLASPSLVSQHLIRPLMGMS

Mouse                         GLILRVQSELSGLPFSWHFHCIPASSSLVSQHLIHPLMGVS

Rat                           VLILRVRSELSGLPFNWHFHCLPASSLLVSQHLICPLMGVS

Zebrafish                     SLTVKLKSELAGLPFYWEFRCTTTPVAVVCRQLVRPLLAMT

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 – 299 Non-homologous end-joining factor 1
Region 1 – 135 Globular head
Site 115 – 115 Leu-lock
Modified residue 132 – 132 Phosphoserine; by PRKDC
Mutagenesis 105 – 105 I -> S. Does not affect ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4.
Mutagenesis 111 – 111 E -> A. Does not affect ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4.
Mutagenesis 111 – 111 E -> K. Does not affect interaction with XRCC4.
Mutagenesis 115 – 115 L -> AD. Impaired ability to repair double-strand breaks (DSBs). Abolished interaction with XRCC4. Abolished ability to bridge DNA.
Mutagenesis 115 – 115 L -> D. Abolished ability to repair double-strand breaks (DSBs). Abolished ability to participate in V(D)J recombination. Abolished interaction with XRCC4.
Mutagenesis 116 – 116 P -> D. Does not affect ability to participate in V(D)J recombination.
Mutagenesis 117 – 117 F -> A. Does not affect ability to participate in V(D)J recombination.
Mutagenesis 117 – 117 F -> D. Abolished ability to participate in V(D)J recombination.
Mutagenesis 118 – 118 Y -> AD. Does not affect ability to participate in V(D)J recombination.
Mutagenesis 119 – 119 W -> A. Abolished ability to participate in V(D)J recombination.
Mutagenesis 123 – 123 C -> R. Abolished ability to repair double-strand breaks (DSBs). Abolished ability to participate in V(D)J recombination.
Mutagenesis 132 – 132 S -> A. In 6A mutant; abolished phosphorylation; does not affect ability to repair double-strand breaks (DSBs), possibly because of redundancy with XRCC4 phosphorylation sites; when associated with A-203, A-245, A-251, A-263 and A-266. In XLF-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with XRCC4 phosphorylation-defective mutant; when associated with A-203, A-245 and A-251.
Mutagenesis 132 – 132 S -> D. In XLF-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with XRCC4 phospho-mimetic mutant; when associated with D-203, D-245 and D-251.
Mutagenesis 135 – 135 L -> A. Does not affect ability to participate in V(D)J recombination.
Mutagenesis 137 – 137 R -> AN. Does not affect ability to participate in V(D)J recombination.
Mutagenesis 138 – 138 P -> A. Does not affect ability to participate in V(D)J recombination.
Mutagenesis 139 – 139 L -> A. Does not affect ability to participate in V(D)J recombination.
Beta strand 115 – 125


Literature citations

Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly.
Buck D.; Malivert L.; de Chasseval R.; Barraud A.; Fondaneche M.-C.; Sanal O.; Plebani A.; Stephan J.-L.; Hufnagel M.; le Deist F.; Fischer A.; Durandy A.; de Villartay J.-P.; Revy P.;
Cell 124:287-299(2006)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; VARIANTS NHEJ1-SCID GLY-57 AND ARG-123;

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.