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UniProtKB/Swiss-Prot Q06787: Variant p.Arg138Gln

Synaptic functional regulator FMR1
Gene: FMR1
Variant information

Variant position:  138
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 138 (R138Q, p.Arg138Gln).
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:  Fragile X syndrome (FXS) [MIM:300624]: An X-linked dominant disease characterized by moderate to severe mental retardation, macroorchidism (enlargement of the testicles), large ears, prominent jaw, and high-pitched, jocular speech. The defect in most patients results from an amplification of a CGG repeat region in the FMR1 gene and abnormal methylation. {ECO:0000269|PubMed:10196376, ECO:0000269|PubMed:11157796, ECO:0000269|PubMed:15380484, ECO:0000269|PubMed:15805463, ECO:0000269|PubMed:17850748, ECO:0000269|PubMed:18093976, ECO:0000269|PubMed:18664458, ECO:0000269|PubMed:23235829, ECO:0000269|PubMed:24204304, ECO:0000269|PubMed:24448548, ECO:0000269|PubMed:24514761, ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25561520, ECO:0000269|PubMed:7633450, ECO:0000269|PubMed:7688265, ECO:0000269|PubMed:8156595, ECO:0000269|PubMed:8401578, ECO:0000269|PubMed:8490650, ECO:0000269|PubMed:9659908}. Note=The disease is caused by mutations affecting 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 FXS; rare variant found in a developmentally delayed male; inhibits nucleosome binding; reduces interaction with KCNMB4; inhibits presynaptic action potential (AP) broadening; does not alter postsynaptic RNA-binding and polyribosome association.
Any additional useful information about the variant.

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



Sequence information

Variant position:  138
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  632
The length of the canonical sequence.

Location on the sequence:   NKPATKDTFHKIKLDVPEDL  R QMCAKEAAHKDFKKAVGAFS
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.

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 – 632 Synaptic functional regulator FMR1
Region 1 – 184 Required for nuclear localization
Turn 135 – 138


Literature citations

A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response.
Alpatov R.; Lesch B.J.; Nakamoto-Kinoshita M.; Blanco A.; Chen S.; Stuetzer A.; Armache K.J.; Simon M.D.; Xu C.; Ali M.; Murn J.; Prisic S.; Kutateladze T.G.; Vakoc C.R.; Min J.; Kingston R.E.; Fischle W.; Warren S.T.; Page D.C.; Shi Y.;
Cell 157:869-881(2014)
Cited for: FUNCTION; INTERACTION WITH METHYLATED HISTONE H3; DOMAIN; CHARACTERIZATION OF VARIANT FXS GLN-138; MUTAGENESIS OF THR-102 AND TYR-103;

Identification of novel FMR1 variants by massively parallel sequencing in developmentally delayed males.
Collins S.C.; Bray S.M.; Suhl J.A.; Cutler D.J.; Coffee B.; Zwick M.E.; Warren S.T.;
Am. J. Med. Genet. A 152:2512-2520(2010)
Cited for: VARIANT GLN-138;

Independent role for presynaptic FMRP revealed by an FMR1 missense mutation associated with intellectual disability and seizures.
Myrick L.K.; Deng P.Y.; Hashimoto H.; Oh Y.M.; Cho Y.; Poidevin M.J.; Suhl J.A.; Visootsak J.; Cavalli V.; Jin P.; Cheng X.; Warren S.T.; Klyachko V.A.;
Proc. Natl. Acad. Sci. U.S.A. 112:949-956(2015)
Cited for: VARIANT FXS GLN-138; CHARACTERIZATION OF VARIANT FXS GLN-138; FUNCTION; INTERACTION WITH KCNMB4; DOMAIN;

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.