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UniProtKB/Swiss-Prot P29965: Variant p.Gly227Val

CD40 ligand
Gene: CD40LG
Variant information

Variant position:  227
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 Glycine (G) to Valine (V) at position 227 (G227V, p.Gly227Val).
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 glycine (G) to medium size and hydrophobic (V)
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 HIGM1; decreases ITGA5:ITGB1 and ITGAV:ITGB3 binding of the soluble form; decreases activation of NF-kappa-B signaling.
Any additional useful information about the variant.

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



Sequence information

Variant position:  227
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:   RAANTHSSAKPCGQQSIHLG  G VFELQPGASVFVNVTDPSQV
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                         RAANTHSSAK-PCGQQSIHLGGVFELQPGASVFVNVTDPSQV

                              RAASSRGSSK-PCGQQSIHLGGVFELHPGASVFVNVTDPSQ

Rhesus macaque                RAANTHSSAK-PCGQQSIHLGGVFELQPGASVFVNVTDPSQ

Mouse                         KAANTHSSSQ-LCEQQSVHLGGVFELQAGASVFVNVTEASQ

Rat                           RAANTHSSSK-LCEQQSIHLGGVFELQAGASVFVNVTEASQ

Pig                           RAANTHSSSK-PCGQQSIHLGGVFELQPGASVFVNVTDPSQ

Bovine                        RAANTHSSSK-PCGQQSIHLGGVFELQSGASVFVNVTDPSQ

Cat                           RAANARSSSK-PCGQQSIHLGGVFELHPGASVFVNVTDPSQ

Chicken                       KGLDTHSTSTALCELQSIREGGVFELRQGDMVFVNVTDSTA

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.
Beta strand 218 – 232


Literature citations

Integrin Binding to the Trimeric Interface of CD40L Plays a Critical Role in CD40/CD40L Signaling.
Takada Y.K.; Yu J.; Shimoda M.; Takada Y.;
J. Immunol. 203:1383-1391(2019)
Cited for: FUNCTION AS CD40 AND INTEGRIN LIGAND; CHARACTERIZATION OF VARIANTS HIGM1 CYS-170; ARG-174; ILE-176; ASP-208; TYR-224; ALA-226; VAL-227 AND SER-258; MUTAGENESIS OF TYR-170; HIS-224; GLY-226 AND GLY-252;

CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome.
Allen R.C.; Armitage R.J.; Conley M.E.; Rosenblatt H.; Jenkins N.A.; Copeland N.G.; Bedell M.A.; Edelhoff S.; Disteche C.M.; Simoneaux D.K.; Fanslow W.C.; Belmont J.W.; Spriggs M.K.;
Science 259:990-993(1993)
Cited for: VARIANTS HIGM1 PRO-155; ASN-211 AND VAL-227;

A single strand conformation polymorphism study of CD40 ligand. Efficient mutation analysis and carrier detection for X-linked hyper IgM syndrome.
Lin Q.; Rohrer J.; Allen R.C.; Larche M.; Greene J.M.; Shigeoka A.O.; Gatti R.A.; Derauf D.C.; Belmont J.W.; Conley M.E.;
J. Clin. Invest. 97:196-201(1996)
Cited for: VARIANTS HIGM1 PRO-155 AND VAL-227; VARIANT ARG-219;

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.