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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9BXJ7: Variant p.Thr41Ile

Protein amnionless
Gene: AMN
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Variant information Variant position: help 41 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Threonine (T) to Isoleucine (I) at position 41 (T41I, p.Thr41Ile). 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: help Change from medium size and polar (T) to medium size and hydrophobic (I) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In IGS2; reduced presence at the cell membrane; loss of interaction with CUBN; reduced CUBN expression at the cell surface. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 41 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 453 The length of the canonical sequence.
Location on the sequence: help SKLWVPNTDFDVAANWSQNR T PCAGGAVEFPADKMVSVLVQ 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         SKLWVPNTDFDVAANWSQNRTPCAGGAVEFPADKMVSVLVQ

                              YKLWVPTTDFEAAANWSQNRTPCAGAVVQFPADKAVSVVVR

Mouse                         YKLWVPNTSFDTASNWNQNRTPCAGDAVQFPADKMVSVLVR

Pig                           YKLWVPNTYFDAADNWSQNQTPCAGAAVKFPADKMVSVLVR

Drosophila                    TKWYGGGMDFNDPTAWLDDHLPCAQDLVVFPEYYPALLPLP

Sequence annotation in neighborhood: help 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 20 – 453 Protein amnionless
Topological domain 20 – 357 Extracellular
Glycosylation 35 – 35 N-linked (GlcNAc...) asparagine
Mutagenesis 35 – 35 N -> Q. Loss of expression at the cell membrane.
Mutagenesis 37 – 37 S -> A. No effect.
Mutagenesis 59 – 59 L -> P. Loss of interaction with CUBN and strongly reduced CUBN expression at the cell surface.



Literature citations
Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia.
Tanner S.M.; Aminoff M.; Wright F.A.; Liyanarachchi S.; Kuronen M.; Saarinen A.; Massika O.; Mandel H.; Broch H.; de la Chapelle A.;
Nat. Genet. 33:426-429(2003)
Cited for: PROTEIN SEQUENCE OF 300-323 AND 393-453; TISSUE SPECIFICITY; VARIANT IGS2 ILE-41; FUNCTION; ALTERNATIVE PRODUCTS; Structural assembly of the megadalton-sized receptor for intestinal vitamin B12 uptake and kidney protein reabsorption.
Larsen C.; Etzerodt A.; Madsen M.; Skjodt K.; Moestrup S.K.; Andersen C.B.F.;
Nat. Commun. 9:5204-5204(2018)
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 20-357 IN COMPLEX WITH CUBN; CHARACTERIZATION OF VARIANT IGS2 ILE-41; SUBUNIT; SUBCELLULAR LOCATION; TOPOLOGY; DISULFIDE BONDS; MUTAGENESIS OF ASN-35 AND SER-37; Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns.
Tanner S.M.; Sturm A.C.; Baack E.C.; Liyanarachchi S.; de la Chapelle A.;
Orphanet J. Rare Dis. 7:56-56(2012)
Cited for: VARIANTS IGS2 ILE-41 AND PHE-234; Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.
Udagawa T.; Harita Y.; Miura K.; Mitsui J.; Ode K.L.; Morishita S.; Urae S.; Kanda S.; Kajiho Y.; Tsurumi H.; Ueda H.R.; Tsuji S.; Saito A.; Oka A.;
Sci. Rep. 8:2351-2351(2018)
Cited for: FUNCTION; INTERACTION WITH CUBN; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS IGS2 ILE-41; LYS-69 AND PHE-234; MUTAGENESIS OF LEU-59 AND GLY-254;
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.