Incidental Mutation 'A4554:Chst4'
ID109
Institutional Source Beutler Lab
Gene Symbol Chst4
Ensembl Gene ENSMUSG00000035930
Gene Namecarbohydrate (chondroitin 6/keratan) sulfotransferase 4
SynonymsGST-3, HEC-GlcNAc6ST, high endothelial cell GlcNAC-6-sulphotransferase
Accession Numbers

Genbank: NM_011998;  MGI: 1349479

Is this an essential gene? Probably non essential (E-score: 0.060) question?
Stock #A4554 of strain gemini
Quality Score
Status Validated
Chromosome8
Chromosomal Location110029153-110039740 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) G to T at 110029888 bp
ZygosityHomozygous
Amino Acid Change Glutamine to Lysine at position 448 (Q448K)
Ref Sequence ENSEMBL: ENSMUSP00000148741 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000109222] [ENSMUST00000211894] [ENSMUST00000212934]
Predicted Effect probably benign
Transcript: ENSMUST00000109222
AA Change: Q365K

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000104845
Gene: ENSMUSG00000035930
AA Change: Q365K

DomainStartEndE-ValueType
transmembrane domain 7 29 N/A INTRINSIC
Pfam:Sulfotransfer_3 41 296 6.4e-15 PFAM
Pfam:Sulfotransfer_1 41 357 2.4e-26 PFAM
low complexity region 370 378 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000211894
AA Change: Q448K

PolyPhen 2 Score 0.085 (Sensitivity: 0.93; Specificity: 0.85)
Predicted Effect probably benign
Transcript: ENSMUST00000212934
Meta Mutation Damage Score 0.0732 question?
Coding Region Coverage
  • 1x: 85.5%
  • 3x: 63.0%
Validation Efficiency 84% (92/109)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes an N-acetylglucosamine 6-O sulfotransferase. The encoded enzyme transfers sulfate from 3'phosphoadenosine 5'phospho-sulfate to the 6-hydroxyl group of N-acetylglucosamine on glycoproteins. This protein is localized to the Golgi and is involved in the modification of glycan structures on ligands of the lymphocyte homing receptor L-selectin. Alternate splicing in the 5' UTR results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2009]
PHENOTYPE: Mice homozygous for disruptions in this gene do not accumulate lymphocytes in peripheral lymph nodes to as great an extent as normal. The animals are phenotypically normal otherwise. [provided by MGI curators]
Allele List at MGI

All alleles(2) : Targeted, knock-out(1) Targeted, other(1)

Other mutations in this stock
Total: 18 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Asap1 T C 15: 64,124,711 probably benign Het
Bpifb5 A T 2: 154,227,180 Y139F possibly damaging Homo
Chd2 A C 7: 73,480,968 V782G probably benign Homo
Dido1 T C 2: 180,675,371 K8E probably damaging Homo
Evpl A G 11: 116,220,834 L2010P probably damaging Homo
Fgl2 A G 5: 21,372,778 E21G probably benign Homo
Greb1l A T 18: 10,532,862 M919L possibly damaging Homo
Kel T A 6: 41,697,419 D359V possibly damaging Homo
Lmtk2 A G 5: 144,166,317 D298G possibly damaging Homo
Masp1 A T 16: 23,454,940 probably null Homo
Mrgprb8 A T 7: 48,389,408 I276F probably damaging Homo
Nde1 T C 16: 14,188,410 probably benign Homo
Rbck1 G T 2: 152,319,172 N385K probably damaging Homo
Senp6 G T 9: 80,148,458 probably benign Het
Tm4sf4 T A 3: 57,437,767 probably null Homo
Ubn2 A T 6: 38,484,110 H488L probably damaging Homo
Vmn2r120 A G 17: 57,525,715 F155L probably benign Homo
Vmn2r65 T A 7: 84,946,583 T298S probably damaging Homo
Other mutations in Chst4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01077:Chst4 APN 8 110029965 missense probably benign 0.14
R0091:Chst4 UTSW 8 110030665 missense probably damaging 1.00
R0373:Chst4 UTSW 8 110030394 missense probably damaging 1.00
R1171:Chst4 UTSW 8 110030623 missense probably damaging 1.00
R1577:Chst4 UTSW 8 110029844 missense probably benign 0.00
R2377:Chst4 UTSW 8 110030172 missense possibly damaging 0.80
R3421:Chst4 UTSW 8 110030406 missense probably damaging 1.00
R5514:Chst4 UTSW 8 110029974 missense probably damaging 1.00
R6793:Chst4 UTSW 8 110030067 missense probably damaging 1.00
R7141:Chst4 UTSW 8 110030839 missense probably damaging 1.00
R7146:Chst4 UTSW 8 110030731 missense probably damaging 1.00
R7183:Chst4 UTSW 8 110029998 missense possibly damaging 0.72
R7732:Chst4 UTSW 8 110029882 nonsense probably null
Nature of Mutation
DNA sequencing using the SOLiD technique identified a C to A transversion at position 1187 of the Chst4 transcript. Two transcripts of the Chst4 gene are displayed on Ensembl. The mutated nucleotide causes a glutamine to lysine substitution at amino acid 365 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Chst4 gene encodes a 388 amino acid protein that is a single pass type II membrane protein localized to the Golgi, and is known as carbohydrate sulfotransferase 4 (CHST4). CHST4 catalyzes the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues within mucin-associated glycans that ultimately serve as L-selectin ligands. L-selectin ligands are present in high endothelial cells (HEVs) and play a central role in lymphocyte homing at sites of inflammation. CHST4 participates in the biosynthesis of L-selectin ligand sialyl 6-sulfo Lewis X on L-selectin counter receptors CD43, GlyCAM-1 and MAdCAM-1, and is also involved in the biosynthesis of L-selectin ligand recognized by MECA-79 antibody. CHST4 plays a central role in lymphocyte trafficking during chronic inflammation, and has a catalytic preference for core 2-branched mucin-type O-glycans. Its substrate specificity may be influenced by its subcellular location (Uniprot Q9R1I1). Mice homozygous for disruptions in this gene do not accumulate lymphocytes in peripheral lymph nodes to as great an extent as normal. The animals are phenotypically normal otherwise.
 
The Q365K change is predicted to be benign by the PolyPhen program.
Posted On2010-03-16