UniProtKB/SwissProt variant VAR

Variant information

Variant position:

154

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

Type of variant:

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:

From Isoleucine (I) to Threonine (T) at position 154 (I154T, p.Ile154Thr).

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 medium size and hydrophobic (I) to medium size and polar (T)

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

Variant description:

In NEDSHBA; does not rescue axon outgrowth defects when expressed in an heterologous system; decreased protein abundance; increased proteasomal degradation; decreased homodimerization; decreased localization to the cell membrane.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1114167298 [ dbSNP | Ensembl ]

Sequence information

Variant position:

154

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

Protein sequence length:

915

The length of the canonical sequence.

Location on the sequence:

VRCTNGEPPVFVKPEKVVGV I GASGSSVSIMVANILRLFQI

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                         VRCTNGEPPVFVKPEKVVGVIGASGSSVSIMVANILRLFQI

Mouse                         VRCTNGEPPVFVKPEKVVGVIGASGSSVSIMVANILRLFQI

Rat                           VRCTNGEPPVFVKPEKVVGVIGASGSSVSIMVANILRLFQI

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.

Type	Positions	Description
Chain	35 – 915	Metabotropic glutamate receptor 7
Topological domain	35 – 590	Extracellular
Binding site	159 – 159	Glutamate
Beta strand	150 – 154

Literature citations

Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate.
Charng W.L.; Karaca E.; Coban Akdemir Z.; Gambin T.; Atik M.M.; Gu S.; Posey J.E.; Jhangiani S.N.; Muzny D.M.; Doddapaneni H.; Hu J.; Boerwinkle E.; Gibbs R.A.; Rosenfeld J.A.; Cui H.; Xia F.; Manickam K.; Yang Y.; Faqeih E.A.; Al Asmari A.; Saleh M.A.; El-Hattab A.W.; Lupski J.R.;
BMC Med. Genomics 9:42-42(2016)
Cited for: INVOLVEMENT IN NEDSHBA; VARIANTS NEDSHBA THR-154; TRP-658 AND LYS-675;

Biallelic GRM7 variants cause epilepsy, microcephaly, and cerebral atrophy.
Marafi D.; Mitani T.; Isikay S.; Hertecant J.; Almannai M.; Manickam K.; Abou Jamra R.; El-Hattab A.W.; Rajah J.; Fatih J.M.; Du H.; Karaca E.; Bayram Y.; Punetha J.; Rosenfeld J.A.; Jhangiani S.N.; Boerwinkle E.; Akdemir Z.C.; Erdin S.; Hunter J.V.; Gibbs R.A.; Pehlivan D.; Posey J.E.; Lupski J.R.;
Ann. Clin. Transl. Neurol. 7:610-627(2020)
Cited for: VARIANTS NEDSHBA THR-154; 586-TRP--ILE-915 DEL; GLN-658; TRP-658; 659-ARG--ILE-915 DEL; LYS-675 AND LYS-891;

A GRM7 mutation associated with developmental delay reduces mGlu7 expression and produces neurological phenotypes.
Fisher N.M.; Alhashim A.; Buch A.B.; Badivuku H.; Samman M.M.; Weiss K.M.; Cestero G.I.; Does M.D.; Rook J.M.; Lindsley C.W.; Conn P.J.; Gogliotti R.G.; Niswender C.M.;
JCI Insight 6:0-0(2021)
Cited for: VARIANT NEDSHBA THR-154; CHARACTERIZATION OF VARIANT NEDSHBA THR-154; SUBUNIT;

Pathogenic GRM7 mutations associated with neurodevelopmental disorders impair axon outgrowth and presynaptic terminal development.
Song J.M.; Kang M.; Park D.H.; Park S.; Lee S.; Suh Y.H.;
J. Neurosci. 41:2344-2359(2021)
Cited for: CHARACTERIZATION OF VARIANTS NEDSHBA THR-154 AND 586-TRP--ILE-915 DEL; FUNCTION; SUBUNIT; SUBCELLULAR LOCATION; GLYCOSYLATION; MUTAGENESIS OF ARG-622; ARG-658 AND THR-675;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q14831: Variant p.Ile154Thr