UniProtKB/Swiss-Prot P39210: Variant p.Pro98Leu

Protein Mpv17
Gene: MPV17
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Variant information Variant position:

98 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 Proline (P) to Leucine (L) at position 98 (P98L, p.Pro98Leu). 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:

-3 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 MTDPS6 and CMT2EE; results in incomplete closing of the channel. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs267607258 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

PGTTKVDALKKMLLDQGGFA P CFLGCFLPLVGALNGLSAQD 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                         PGTTKV--DALKKMLLDQGGFAPCFLGCFLPLVGALNGLSAQD

Mouse                         PGTTKV--HALKKMLLDQGGFAPCFLGCFLPLVGILNGMSA

Rat                           PGTTKV--NALKKMLLDQGGFAPCFLGCFLPLVGVLNGMSA

Bovine                        PGTTKV--DALKKMLLDQGGFAPCFLGCFLPLVGTLNGLSA

Xenopus laevis                PGSGKP--VALKKMLLDQVAFAPCFLGCFLSIASALNGLSG

Zebrafish                     TGGTKS--AALKKMLVDQVGFAPCFLGAFLGITGTLNGLTV

Caenorhabditis elegans        GNNKSL--LLVKKLCIDQLCFSPCFNAAILFNLRLLQHQSA

Drosophila                    PKTYSPMRRGVTKMLVDQTLFAPPFTMAMSFLVPLSNGEPI

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	1 – 176	Protein Mpv17
Transmembrane	94 – 114	Helical
Site	92 – 92	Determines ion selectivity
Mutagenesis	80 – 80	T -> A. Does not affect gating properties of the channel.
Mutagenesis	92 – 92	D -> K. Affects ion selectivity of the channel.
Mutagenesis	99 – 99	C -> A. Does not affect conductance and gating properties of the channel.

Literature citations
The human mitochondrial DNA depletion syndrome gene MPV17 encodes a non-selective channel that modulates membrane potential.
Antonenkov V.D.; Isomursu A.; Mennerich D.; Vapola M.H.; Weiher H.; Kietzmann T.; Hiltunen J.K.;
J. Biol. Chem. 290:13840-13861(2015)
Cited for: FUNCTION; MUTAGENESIS OF THR-80; ASP-92 AND CYS-99; CHARACTERIZATION OF VARIANT MTDPS6 LEU-98; MPV17-associated hepatocerebral mitochondrial DNA depletion syndrome: new patients and novel mutations.
El-Hattab A.W.; Li F.Y.; Schmitt E.; Zhang S.; Craigen W.J.; Wong L.J.;
Mol. Genet. Metab. 99:300-308(2010)
Cited for: VARIANTS MTDPS6 GLN-50; GLU-88; LYS-88 DEL; LEU-91 DEL; ARG-94; LEU-98 AND ASP-162; MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle.
Blakely E.L.; Butterworth A.; Hadden R.D.; Bodi I.; He L.; McFarland R.; Taylor R.W.;
Neuromuscul. Disord. 22:587-591(2012)
Cited for: VARIANT CMT2EE LEU-98; Clinical, biochemical, cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene.
Uusimaa J.; Evans J.; Smith C.; Butterworth A.; Craig K.; Ashley N.; Liao C.; Carver J.; Diot A.; Macleod L.; Hargreaves I.; Al-Hussaini A.; Faqeih E.; Asery A.; Al Balwi M.; Eyaid W.; Al-Sunaid A.; Kelly D.; van Mourik I.; Ball S.; Jarvis J.; Mulay A.; Hadzic N.; Samyn M.; Baker A.; Rahman S.; Stewart H.; Morris A.A.; Seller A.; Fratter C.; Taylor R.W.; Poulton J.;
Eur. J. Hum. Genet. 22:184-191(2014)
Cited for: VARIANTS MTDPS6 ARG-21; PRO-23; PRO-36; TRP-41; 44-GLN--LEU-176 DEL; ARG-64; PRO-93 AND LEU-98; Mitochondrial DNA depletion syndrome causing liver failure.
Bijarnia-Mahay S.; Mohan N.; Goyal D.; Verma I.C.;
Indian Pediatr. 51:666-668(2014)
Cited for: VARIANTS MTDPS6 LEU-98 AND 136-TYR--LEU-176 DEL; Adult-onset fatal neurohepatopathy in a woman caused by MPV17 mutation.
Mendelsohn B.A.; Mehta N.; Hameed B.; Pekmezci M.; Packman S.; Ralph J.;
JIMD Rep. 13:37-41(2014)
Cited for: VARIANT CMT2EE LEU-98; MPV17 mutations in patients with hepatocerebral mitochondrial DNA depletion syndrome.
Kim J.; Kang E.; Kim Y.; Kim J.M.; Lee B.H.; Murayama K.; Kim G.H.; Choi I.H.; Kim K.M.; Yoo H.W.;
Mol. Genet. Metab. Rep. 8:74-76(2016)
Cited for: VARIANTS MTDPS6 GLU-66; ARG-94 AND LEU-98; A comprehensive genomic analysis reveals the genetic landscape of mitochondrial respiratory chain complex deficiencies.
Kohda M.; Tokuzawa Y.; Kishita Y.; Nyuzuki H.; Moriyama Y.; Mizuno Y.; Hirata T.; Yatsuka Y.; Yamashita-Sugahara Y.; Nakachi Y.; Kato H.; Okuda A.; Tamaru S.; Borna N.N.; Banshoya K.; Aigaki T.; Sato-Miyata Y.; Ohnuma K.; Suzuki T.; Nagao A.; Maehata H.; Matsuda F.; Higasa K.; Nagasaki M.; Yasuda J.; Yamamoto M.; Fushimi T.; Shimura M.; Kaiho-Ichimoto K.; Harashima H.; Yamazaki T.; Mori M.; Murayama K.; Ohtake A.; Okazaki Y.;
PLoS Genet. 12:E1005679-E1005679(2016)
Cited for: VARIANT MTDPS6 LEU-98; MPV17-related mitochondrial DNA maintenance defect: New cases and review of clinical, biochemical, and molecular aspects.
El-Hattab A.W.; Wang J.; Dai H.; Almannai M.; Staufner C.; Alfadhel M.; Gambello M.J.; Prasun P.; Raza S.; Lyons H.J.; Afqi M.; Saleh M.A.M.; Faqeih E.A.; Alzaidan H.I.; Alshenqiti A.; Flore L.A.; Hertecant J.; Sacharow S.; Barbouth D.S.; Murayama K.; Shah A.A.; Lin H.C.; Wong L.C.;
Hum. Mutat. 39:461-470(2018)
Cited for: VARIANTS MTDPS6 ARG-21; TRP-50; LYS-88 DEL; LEU-91 DEL; GLY-92; PRO-93; ASP-95; LEU-98; 99-CYS--LEU-176 DEL AND MET-154;

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.