UniProtKB/Swiss-Prot O95202: Variant p.Ile305Leu

Mitochondrial proton/calcium exchanger protein
Gene: LETM1
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Variant information Variant position:

305 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 Isoleucine (I) to Leucine (L) at position 305 (I305L, p.Ile305Leu). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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:

No effect on mitochondrial potassium ion transmembrane transport; it fully rescues defective proton/potassium exchange in letm1-deficient yeast. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs775882709 [ dbSNP | Ensembl ]

Sequence information Variant position:

305 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

739 The length of the canonical sequence.
Location on the sequence:

DFSVFFQKIRETGERPSNEE I MRFSKLFEDELTLDNLTRPQ 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                         DFSVFFQKIRETGERPSNEEIMRFSKLFEDELTLDNLTRPQ

Mouse                         DFSAFFQKIRETGERPSNEEIMRFSKLFEDELTLDNLTRPQ

Rat                           DFSAFFQKIRETGERPSNEEIMRFSKLFEDELTLDNLTRPQ

Bovine                        DFSVFFQKIRETGERPSNEEIMRFSKLFEDELTLDNLTRPQ

Chicken                       DFSTFFQKIRETGERPSNEEILRFSKLFEDELTLDNLTRPQ

Xenopus tropicalis            EFATFFQKIRSTGERPSNEEIVRFSKLFEDELTLDNLTRPQ

Zebrafish                     EFSTFFQKIRDSGEIPSNEQIIRFSKLFEDELTLDNLTRPQ

Drosophila                    QFEAFFTKIRNPTEPVSNDEIIKFAKRFDDEITLDSLSREQ

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	116 – 739	Mitochondrial proton/calcium exchanger protein
Topological domain	230 – 739	Mitochondrial matrix
Domain	252 – 537	Letm1 RBD
Alternative sequence	295 – 739	Missing. In isoform 2 and isoform 3.

Literature citations
Bi-allelic LETM1 variants perturb mitochondrial ion homeostasis leading to a clinical spectrum with predominant nervous system involvement.
Kaiyrzhanov R.; Mohammed S.E.M.; Maroofian R.; Husain R.A.; Catania A.; Torraco A.; Alahmad A.; Dutra-Clarke M.; Groenborg S.; Sudarsanam A.; Vogt J.; Arrigoni F.; Baptista J.; Haider S.; Feichtinger R.G.; Bernardi P.; Zulian A.; Gusic M.; Efthymiou S.; Bai R.; Bibi F.; Horga A.; Martinez-Agosto J.A.; Lam A.; Manole A.; Rodriguez D.P.; Durigon R.; Pyle A.; Albash B.; Dionisi-Vici C.; Murphy D.; Martinelli D.; Bugiardini E.; Allis K.; Lamperti C.; Reipert S.; Risom L.; Laugwitz L.; Di Nottia M.; McFarland R.; Vilarinho L.; Hanna M.; Prokisch H.; Mayr J.A.; Bertini E.S.; Ghezzi D.; Oestergaard E.; Wortmann S.B.; Carrozzo R.; Haack T.B.; Taylor R.W.; Spinazzola A.; Nowikovsky K.; Houlden H.;
Am. J. Hum. Genet. 109:1692-1712(2022)
Cited for: VARIANTS CONDMIM LYS-252 DEL; ASN-293; GLN-294; SER-300; ASN-358; PRO-380; HIS-393 AND ARG-587; CHARACTERIZATION OF VARIANTS CONDMIM LYS-252 DEL; ASN-293; GLN-294; SER-300; ASN-358; PRO-380 AND ARG-587; VARIANT LEU-305; CHARACTERIZATION OF VARIANT LEU-305; INVOLVEMENT IN CONDMIM; FUNCTION; TRANSPORTER ACTIVITY;

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.