UniProtKB/Swiss-Prot Q12756: Variant p.Thr99Met

Kinesin-like protein KIF1A
Gene: KIF1A
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Variant information Variant position:

99 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 Threonine (T) to Methionine (M) at position 99 (T99M, p.Thr99Met). 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 polar (T) to medium size and hydrophobic (M) 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 NESCAVS; affects subcellular location; reduced distal localization and increased accumulation throughout the cell body and proximal neurites; disrupts microtubule motility. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs387906799 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

1690 The length of the canonical sequence.
Location on the sequence:

EEMLQHAFEGYNVCIFAYGQ T GAGKSYTMMGKQEKDQQGII 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                         EEMLQHAFEGYNVCIFAYGQTGAGKSYTMMGKQEKDQQGII

Mouse                         EEMLQHAFEGYNVCIFAYGQTGAGKSYTMMGKQEKDQQGII

Rat                           EEMLQHAFEGYNVCIFAYGQTGAGKSYTMMGKQEKDQQGII

Drosophila                    EEMLQHSFDGYNVCIFAYGQTGAGKSYTMMGRQEEQQEGII

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 – 1690	Kinesin-like protein KIF1A
Domain	5 – 354	Kinesin motor
Binding site	97 – 104
Beta strand	98 – 102

Literature citations
Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.
Hamdan F.F.; Gauthier J.; Araki Y.; Lin D.T.; Yoshizawa Y.; Higashi K.; Park A.R.; Spiegelman D.; Dobrzeniecka S.; Piton A.; Tomitori H.; Daoud H.; Massicotte C.; Henrion E.; Diallo O.; Shekarabi M.; Marineau C.; Shevell M.; Maranda B.; Mitchell G.; Nadeau A.; D'Anjou G.; Vanasse M.; Srour M.; Lafreniere R.G.; Drapeau P.; Lacaille J.C.; Kim E.; Lee J.R.; Igarashi K.; Huganir R.L.; Rouleau G.A.; Michaud J.L.;
Am. J. Hum. Genet. 88:306-316(2011)
Cited for: TISSUE SPECIFICITY; SUBCELLULAR LOCATION; VARIANT NESCAVS MET-99; CHARACTERIZATION OF VARIANT NESCAVS MET-99; KIF1A mutation in a patient with progressive neurodegeneration.
Okamoto N.; Miya F.; Tsunoda T.; Yanagihara K.; Kato M.; Saitoh S.; Yamasaki M.; Kanemura Y.; Kosaki K.;
J. Hum. Genet. 59:639-641(2014)
Cited for: INVOLVEMENT IN NESCAVS; VARIANT NESCAVS MET-99; De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy.
Esmaeeli Nieh S.; Madou M.R.; Sirajuddin M.; Fregeau B.; McKnight D.; Lexa K.; Strober J.; Spaeth C.; Hallinan B.E.; Smaoui N.; Pappas J.G.; Burrow T.A.; McDonald M.T.; Latibashvili M.; Leshinsky-Silver E.; Lev D.; Blumkin L.; Vale R.D.; Barkovich A.J.; Sherr E.H.;
Ann. Clin. Transl. Neurol. 2:623-635(2015)
Cited for: VARIANTS MET-46; ASN-136; ILE-187; MET-205; ILE-220; ASP-233; VAL-336 AND HIS-355; VARIANTS NESCAVS MET-99; CYS-216; HIS-216; LYS-253 AND TRP-316; CHARACTERIZATION OF VARIANTS NESCAVS MET-99; CYS-216 AND LYS-253; CHARACTERIZATION OF VARIANT SPG30B VAL-255; CHARACTERIZATION OF VARIANT ILE-220; De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy.
Lee J.R.; Srour M.; Kim D.; Hamdan F.F.; Lim S.H.; Brunel-Guitton C.; Decarie J.C.; Rossignol E.; Mitchell G.A.; Schreiber A.; Moran R.; Van Haren K.; Richardson R.; Nicolai J.; Oberndorff K.M.; Wagner J.D.; Boycott K.M.; Rahikkala E.; Junna N.; Tyynismaa H.; Cuppen I.; Verbeek N.E.; Stumpel C.T.; Willemsen M.A.; de Munnik S.A.; Rouleau G.A.; Kim E.; Kamsteeg E.J.; Kleefstra T.; Michaud J.L.;
Hum. Mutat. 36:69-78(2015)
Cited for: VARIANTS NESCAVS LEU-58; MET-99; ASP-102; PHE-144; CYS-167; PRO-202; ARG-215; PRO-216; GLN-249; LYS-253 AND TRP-316; CHARACTERIZATION OF VARIANTS NESCAVS MET-99; PRO-202; ARG-215; PRO-216 AND LYS-253; CHARACTERIZATION OF VARIANTS SPG30B VAL-255 AND GLY-350; SUBCELLULAR LOCATION; De novo dominant variants affecting the motor domain of KIF1A are a cause of PEHO syndrome.
Langlois S.; Tarailo-Graovac M.; Sayson B.; Droegemoeller B.; Swenerton A.; Ross C.J.; Wasserman W.W.; van Karnebeek C.D.;
Eur. J. Hum. Genet. 24:949-953(2016)
Cited for: INVOLVEMENT IN NESCAVS; VARIANT NESCAVS MET-99; Expansion of the phenotypic spectrum of de novo missense variants in kinesin family member 1A (KIF1A).
Kaur S.; Van Bergen N.J.; Verhey K.J.; Nowell C.J.; Budaitis B.; Yue Y.; Ellaway C.; Brunetti-Pierri N.; Cappuccio G.; Bruno I.; Boyle L.; Nigro V.; Torella A.; Roscioli T.; Cowley M.J.; Massey S.; Sonawane R.; Burton M.D.; Schonewolf-Greulich B.; Tuemer Z.; Chung W.K.; Gold W.A.; Christodoulou J.;
Hum. Mutat. 41:1761-1774(2020)
Cited for: INVOLVEMENT IN KAND; VARIANTS KAND ARG-92 AND GLU-248; VARIANT NESCAVS MET-99; VARIANT SPG30 LEU-305; CHARACTERIZATION OF VARIANTS KAND ARG-92 AND GLU-248; CHARACTERIZATION OF VARIANT SPG30A LEU-305; SUBCELLULAR LOCATION; Genotype and defects in microtubule-based motility correlate with clinical severity in KIF1A-associated neurological disorder.
Boyle L.; Rao L.; Kaur S.; Fan X.; Mebane C.; Hamm L.; Thornton A.; Ahrendsen J.T.; Anderson M.P.; Christodoulou J.; Gennerich A.; Shen Y.; Chung W.K.;
HGG Adv. 2:0-0(2021)
Cited for: INVOLVEMENT IN KAND; VARIANTS KAND CYS-13; HIS-13; ASP-54; ASP-89; THR-103; VAL-117; LYS-148; TYR-151; CYS-155; VAL-156; HIS-157; PRO-171; GLY-179; GLU-199; SER-203; VAL-206; THR-210; HIS-211; ASN-214; TYR-217; CYS-229; MET-247; GLY-248; ARG-251; PRO-254; GLN-267; SER-272; LEU-274; PRO-275; PRO-278; ARG-279; ASP-279; CYS-306; GLY-307; PRO-314; GLN-316 AND ASP-475; VARIANTS NESCAVS LEU-58; MET-99; PHE-186; ARG-199; ARG-215; CYS-216; HIS-216; LYS-253; GLN-254; TRP-254; GLN-307; PRO-307; TRP-316 AND MET-344; VARIANTS SPG30A GLN-11; TRP-11; SER-102; MET-258 AND LEU-305; CHARACTERIZATION OF VARIANTS KAND HIS-13; ASP-89; SER-117; TYR-217; GLY-248; ARG-251; PRO-254; LEU-274; PRO-278 AND MET-344; CHARACTERIZATION OF VARIANTS NESCAVS MET-99; LYS-253; GLN-254; TRP-254; PRO-307 AND TRP-316; CHARACTERIZATION OF VARIANT SPG30A SER-102; FUNCTION; SUBCELLULAR LOCATION;

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.