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UniProtKB/Swiss-Prot Q9Y672: Variant p.Ser304Phe

Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase
Gene: ALG6
Variant information

Variant position:  304
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LB/B
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 Serine (S) to Phenylalanine (F) at position 304 (S304F, p.Ser304Phe).
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 polar (S) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  May act as disease modifier and exacerbate clinical severity in patients with a congenital disorder of glycosylation; slightly decreased function as shown by rescue experiments of defective glycosylation in an alg6-deficient S.cerevisiae strain.
Any additional useful information about the variant.

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



Sequence information

Variant position:  304
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  507
The length of the canonical sequence.

Location on the sequence:   VFLKIKDILPRHIQLIMSFC  S TFLSLLPACIKLILQPSSKG
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                         VFLKIKDILPRHIQLI-MSFCSTFLSLLPACIKLILQPSSK-G

Mouse                         VFLKIKDTLPRHIQIA-ISFCFTLLSLLPACIKLTVRPSCK

Rat                           VFLKIKDILPRHIQIA-ISFCFTFLSLLPACIKLTVQPSAK

Chicken                       VLIKIKNVVSPQTQLK-LSFAVTFLSLLPTCIKLTVQPSLR

Caenorhabditis elegans        FILK---RLPLQSVQIYISTALVLAGSAPSLLVLFLRPTEK

Drosophila                    VVWKLKKHISNDQMAL-VCIACTLIASLPTNVLLFRRRTNV

Slime mold                    IIINVKNLFTTDQLIK-ICLILTLVTMLPLVYGIKRIPKNK

Baker's yeast                 VFVKYKERFTIQQLQL-YSLIATVIGFLPAMIMTLLHPKKH

Fission yeast                 TVFKIREVFTLHQLQV-ISLIFTLISILPSCVILFLYPRKR

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 – 507 Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase
Transmembrane 298 – 318 Helical


Literature citations

A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic.
Imbach T.; Burda P.; Kuhnert P.; Wevers R.A.; Aebi M.; Berger E.G.; Hennet T.;
Proc. Natl. Acad. Sci. U.S.A. 96:6982-6987(1999)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANT CDG1C VAL-333; VARIANT PHE-304;

Submission
Mao Y.M.; Xie Y.; Zheng Z.H.;
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANT PHE-304;

Complete sequencing and characterization of 21,243 full-length human cDNAs.
Ota T.; Suzuki Y.; Nishikawa T.; Otsuki T.; Sugiyama T.; Irie R.; Wakamatsu A.; Hayashi K.; Sato H.; Nagai K.; Kimura K.; Makita H.; Sekine M.; Obayashi M.; Nishi T.; Shibahara T.; Tanaka T.; Ishii S.; Yamamoto J.; Saito K.; Kawai Y.; Isono Y.; Nakamura Y.; Nagahari K.; Murakami K.; Yasuda T.; Iwayanagi T.; Wagatsuma M.; Shiratori A.; Sudo H.; Hosoiri T.; Kaku Y.; Kodaira H.; Kondo H.; Sugawara M.; Takahashi M.; Kanda K.; Yokoi T.; Furuya T.; Kikkawa E.; Omura Y.; Abe K.; Kamihara K.; Katsuta N.; Sato K.; Tanikawa M.; Yamazaki M.; Ninomiya K.; Ishibashi T.; Yamashita H.; Murakawa K.; Fujimori K.; Tanai H.; Kimata M.; Watanabe M.; Hiraoka S.; Chiba Y.; Ishida S.; Ono Y.; Takiguchi S.; Watanabe S.; Yosida M.; Hotuta T.; Kusano J.; Kanehori K.; Takahashi-Fujii A.; Hara H.; Tanase T.-O.; Nomura Y.; Togiya S.; Komai F.; Hara R.; Takeuchi K.; Arita M.; Imose N.; Musashino K.; Yuuki H.; Oshima A.; Sasaki N.; Aotsuka S.; Yoshikawa Y.; Matsunawa H.; Ichihara T.; Shiohata N.; Sano S.; Moriya S.; Momiyama H.; Satoh N.; Takami S.; Terashima Y.; Suzuki O.; Nakagawa S.; Senoh A.; Mizoguchi H.; Goto Y.; Shimizu F.; Wakebe H.; Hishigaki H.; Watanabe T.; Sugiyama A.; Takemoto M.; Kawakami B.; Yamazaki M.; Watanabe K.; Kumagai A.; Itakura S.; Fukuzumi Y.; Fujimori Y.; Komiyama M.; Tashiro H.; Tanigami A.; Fujiwara T.; Ono T.; Yamada K.; Fujii Y.; Ozaki K.; Hirao M.; Ohmori Y.; Kawabata A.; Hikiji T.; Kobatake N.; Inagaki H.; Ikema Y.; Okamoto S.; Okitani R.; Kawakami T.; Noguchi S.; Itoh T.; Shigeta K.; Senba T.; Matsumura K.; Nakajima Y.; Mizuno T.; Morinaga M.; Sasaki M.; Togashi T.; Oyama M.; Hata H.; Watanabe M.; Komatsu T.; Mizushima-Sugano J.; Satoh T.; Shirai Y.; Takahashi Y.; Nakagawa K.; Okumura K.; Nagase T.; Nomura N.; Kikuchi H.; Masuho Y.; Yamashita R.; Nakai K.; Yada T.; Nakamura Y.; Ohara O.; Isogai T.; Sugano S.;
Nat. Genet. 36:40-45(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANT PHE-304;

Submission
Mural R.J.; Istrail S.; Sutton G.G.; Florea L.; Halpern A.L.; Mobarry C.M.; Lippert R.; Walenz B.; Shatkay H.; Dew I.; Miller J.R.; Flanigan M.J.; Edwards N.J.; Bolanos R.; Fasulo D.; Halldorsson B.V.; Hannenhalli S.; Turner R.; Yooseph S.; Lu F.; Nusskern D.R.; Shue B.C.; Zheng X.H.; Zhong F.; Delcher A.L.; Huson D.H.; Kravitz S.A.; Mouchard L.; Reinert K.; Remington K.A.; Clark A.G.; Waterman M.S.; Eichler E.E.; Adams M.D.; Hunkapiller M.W.; Myers E.W.; Venter J.C.;
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]; VARIANT PHE-304;

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANT PHE-304;

Multi-allelic origin of congenital disorder of glycosylation (CDG)-Ic.
Imbach T.; Gruenewald S.; Schenk B.; Burda P.; Schollen E.; Wevers R.A.; Jaeken J.; de Klerk J.B.C.; Berger E.G.; Matthijs G.; Aebi M.; Hennet T.;
Hum. Genet. 106:538-545(2000)
Cited for: VARIANTS CDG1C VAL-333 AND PRO-478; VARIANT PHE-304;

Analysis of multiple mutations in the hALG6 gene in a patient with congenital disorder of glycosylation Ic.
Westphal V.; Schottstaedt C.; Marquardt T.; Freeze H.H.;
Mol. Genet. Metab. 70:219-223(2000)
Cited for: VARIANT CDG1C ILE-299 DEL; VARIANT PHE-304;

The T911C (F304S) substitution in the human ALG6 gene is a common polymorphism and not a causal mutation of CDG-Ic.
Vuillaumier-Barrot S.; Le Bizec C.; Durand G.; Seta N.;
J. Hum. Genet. 46:547-548(2001)
Cited for: VARIANT PHE-304;

A frequent mild mutation in ALG6 may exacerbate the clinical severity of patients with congenital disorder of glycosylation Ia (CDG-Ia) caused by phosphomannomutase deficiency.
Westphal V.; Kjaergaard S.; Schollen E.; Martens K.; Gruenewald S.; Schwartz M.; Matthijs G.; Freeze H.H.;
Hum. Mol. Genet. 11:599-604(2002)
Cited for: CHARACTERIZATION OF VARIANT PHE-304;

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.