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UniProtKB/Swiss-Prot P29965: Variant p.Ala235Pro

CD40 ligand
Gene: CD40LG
Variant information

Variant position:  235
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 Alanine (A) to Proline (P) at position 235 (A235P, p.Ala235Pro).
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 small size and hydrophobic (A) to medium size and hydrophobic (P)
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 HIGM1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  235
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  261
The length of the canonical sequence.

Location on the sequence:   AKPCGQQSIHLGGVFELQPG  A SVFVNVTDPSQVSHGTGFTS
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                         AK-PCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTS

                              SK-PCGQQSIHLGGVFELHPGASVFVNVTDPSQVSHGTGFT

Rhesus macaque                AK-PCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFT

Mouse                         SQ-LCEQQSVHLGGVFELQAGASVFVNVTEASQVIHRVGFS

Rat                           SK-LCEQQSIHLGGVFELQAGASVFVNVTEASQVIHGIGFS

Pig                           SK-PCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFT

Bovine                        SK-PCGQQSIHLGGVFELQSGASVFVNVTDPSQVSHGTGFT

Cat                           SK-PCGQQSIHLGGVFELHPGASVFVNVTDPSQVSHGTGFT

Chicken                       STALCELQSIREGGVFELRQGDMVFVNVTDSTAVNVNPGNT

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 – 261 CD40 ligand, membrane form
Chain 113 – 261 CD40 ligand, soluble form
Topological domain 47 – 261 Extracellular
Glycosylation 240 – 240 N-linked (GlcNAc...) (complex) asparagine; alternate
Glycosylation 240 – 240 N-linked (GlcNAc...) (high mannose) asparagine; alternate
Mutagenesis 224 – 224 H -> E. Decreases ITGA5:ITGB1 binding, B-cell activation, activation of NF-kappa-B signaling, and anti-apoptotic signaling; when associated with E-226 in soluble form. No effect on CD40 binding; when associated with E-226 in soluble form.
Mutagenesis 226 – 226 G -> E. Decreases ITGA5:ITGB1 binding, B-cell activation, activation of NF-kappa-B signaling, and anti-apoptotic signaling; when associated with E-224 in soluble form. No effect on CD40 binding; when associated with E-224 in soluble form.
Mutagenesis 252 – 252 G -> E. Decreases ITGA5:ITGB1 binding, B-cell activation, activation of NF-kappa-B signaling, and anti-apoptotic signaling; in soluble form. No effect on CD40 binding; in soluble form.


Literature citations

The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome.
Aruffo A.; Farrington M.; Hollenbaugh D.; Li X.; Milatovich A.; Nonoyama S.; Bajorath J.; Grosmaire L.S.; Stenkamp R.; Neubauer M.; Roberts R.L.; Noelle R.J.; Ledbetter J.A.; Francke U.; Ochs H.D.;
Cell 72:291-300(1993)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS HIGM1 128-ARG-GLY-129 AND PRO-235;

Mutations of the CD40 ligand gene and its effect on CD40 ligand expression in patients with X-linked hyper IgM syndrome.
Seyama K.; Nonoyama S.; Gangsaas I.; Hollenbaugh D.; Pabst H.F.; Aruffo A.; Ochs H.D.;
Blood 92:2421-2434(1998)
Cited for: VARIANTS HIGM1 SER-116; ASN-147; CYS-170; VAL-227; SER-231; PRO-235; MET-254 AND SER-258;

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.