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UniProtKB/Swiss-Prot O60243: Variant p.Arg306Gln

Heparan-sulfate 6-O-sulfotransferase 1
Gene: HS6ST1
Chromosomal location: 2q21
Variant information

Variant position:  306
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Glutamine (Q) at position 306 (R306Q, p.Arg306Gln).
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 large size and basic (R) to medium size and polar (Q)
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

Involvement in disease:  Hypogonadotropic hypogonadism 15 with or without anosmia (HH15) [MIM:614880]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:21700882, ECO:0000269|PubMed:25077900}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HH15; 15 to 30% reduction in enzymatic activity compared to wild-type.
Any additional useful information about the variant.

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



Sequence information

Variant position:  306
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  411
The length of the canonical sequence.

Location on the sequence:   RGMAFFGLTEFQRKTQYLFE  R TFNLKFIRPFMQYNSTRAGG
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                         RGMAFFGLTEFQRKTQYLFERTFNLKFIRPFMQYNSTRAGG

Mouse                         RGMAFFGLTEFQRKTQYLFERTFNLKFIRPFMQYNSTRAGG

Chicken                       KDMAFFGLTEFQRKTQYLFERTFNLKFIRPFMQYNSTRAGG

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 – 411 Heparan-sulfate 6-O-sulfotransferase 1
Topological domain 38 – 411 Lumenal
Glycosylation 320 – 320 N-linked (GlcNAc...) asparagine


Literature citations

Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism.
Tornberg J.; Sykiotis G.P.; Keefe K.; Plummer L.; Hoang X.; Hall J.E.; Quinton R.; Seminara S.B.; Hughes V.; Van Vliet G.; Van Uum S.; Crowley W.F.; Habuchi H.; Kimata K.; Pitteloud N.; Bulow H.E.;
Proc. Natl. Acad. Sci. U.S.A. 108:11524-11529(2011)
Cited for: FUNCTION; VARIANTS HH15 TRP-306; GLN-306; GLN-323; TRP-382 AND VAL-404; CHARACTERIZATION OF VARIANTS HH15 TRP-306; GLN-306; GLN-323; TRP-382 AND VAL-404;

The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients.
Marcos S.; Sarfati J.; Leroy C.; Fouveaut C.; Parent P.; Metz C.; Wolczynski S.; Gerard M.; Bieth E.; Kurtz F.; Verier-Mine O.; Perrin L.; Archambeaud F.; Cabrol S.; Rodien P.; Hove H.; Prescott T.; Lacombe D.; Christin-Maitre S.; Touraine P.; Hieronimus S.; Dewailly D.; Young J.; Pugeat M.; Hardelin J.P.; Dode C.;
J. Clin. Endocrinol. Metab. 99:E2138-2143(2014)
Cited for: VARIANTS HH15 SER-218; GLN-306 AND TRP-306;

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.