UniProtKB/Swiss-Prot O60701: Variant p.Ile116Thr

UDP-glucose 6-dehydrogenase
Gene: UGDH
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Variant information Variant position:

116 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 116 (I116T, p.Ile116Thr). 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 DEE84; uncertain significance. Any additional useful information about the variant.

Sequence information Variant position:

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

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

YGMGKGRAADLKYIEACARR I VQNSNGYKIVTEKSTVPVRA 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                         YGMGKGRAADLKYIEACARRIVQNSNGYKIVTEKSTVPVRA

Mouse                         YGMGKGRAADLKYIEACARRIVQNSNGYKIVTEKSTVPVRA

Rat                           YGMGKGRAADLKYIEACARRIVQNSNGYKIVTEKSTVPVRA

Bovine                        YGMGKGRAADLKYIEACARRIVQNSHGYKIVTEKSTVPVRA

Chicken                       YGMGKGRAADLKYIEACARRIVQNSNGYKIVTEKSTVPVRA

Caenorhabditis elegans        YGRGKGMAPDLKYVESVSRTIAQYAGGPKIVVEKSTVPVKA

Drosophila                    CGNGKGRAADLKYVESAARMIAEIAQSNKIVVEKSTVPVRA

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 – 494	UDP-glucose 6-dehydrogenase
Modified residue	107 – 107	N6-acetyllysine
Alternative sequence	89 – 155	Missing. In isoform 2.
Mutagenesis	104 – 104	A -> G. Impairs protein folding. Decreases affinity for UDP-glucose. No effect on inhibition by UDP-xylose. No effect on hysteresis and cooperativity.
Mutagenesis	104 – 104	A -> L. No significant effect on catalytic activity and on affinity for NAD and UDP-glucose. Decreases affinity for the inhibitor UDP-xylose. Disrupts hysteresis and cooperativity.
Mutagenesis	131 – 131	T -> A. Reduced affinity for UDP-glucose, and reduced catalytic efficiency.
Mutagenesis	132 – 132	Missing. Nearly abolishes enzyme activity. Stabilizes the enzyme in a low-activity hexameric conformation.
Mutagenesis	136 – 136	A -> M. Stabilizes the active conformation of the hexamer. Decreases affinity for UDP-xylose, but not for UDP-glucose. Disrupts hysteresis and cooperativity.
Helix	107 – 118

Literature citations
Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.
Hengel H.; Bosso-Lefevre C.; Grady G.; Szenker-Ravi E.; Li H.; Pierce S.; Lebigot E.; Tan T.T.; Eio M.Y.; Narayanan G.; Utami K.H.; Yau M.; Handal N.; Deigendesch W.; Keimer R.; Marzouqa H.M.; Gunay-Aygun M.; Muriello M.J.; Verhelst H.; Weckhuysen S.; Mahida S.; Naidu S.; Thomas T.G.; Lim J.Y.; Tan E.S.; Haye D.; Willemsen M.A.A.P.; Oegema R.; Mitchell W.G.; Pierson T.M.; Andrews M.V.; Willing M.C.; Rodan L.H.; Barakat T.S.; van Slegtenhorst M.; Gavrilova R.H.; Martinelli D.; Gilboa T.; Tamim A.M.; Hashem M.O.; Al-Sayed M.D.; Abdulrahim M.M.; Al-Owain M.; Awaji A.; Mahmoud A.A.H.; Faqeih E.A.; Asmari A.A.; Algain S.M.; Jad L.A.; Aldhalaan H.M.; Helbig I.; Koolen D.A.; Riess A.; Kraegeloh-Mann I.; Bauer P.; Gulsuner S.; Stamberger H.; Ng A.Y.J.; Tang S.; Tohari S.; Keren B.; Schultz-Rogers L.E.; Klee E.W.; Barresi S.; Tartaglia M.; Mor-Shaked H.; Maddirevula S.; Begtrup A.; Telegrafi A.; Pfundt R.; Schuele R.; Ciruna B.; Bonnard C.; Pouladi M.A.; Stewart J.C.; Claridge-Chang A.; Lefeber D.J.; Alkuraya F.S.; Mathuru A.S.; Venkatesh B.; Barycki J.J.; Simpson M.A.; Jamuar S.S.; Schoels L.; Reversade B.;
Nat. Commun. 11:595-595(2020)
Cited for: VARIANTS DEE84 CYS-14; THR-24; THR-42; VAL-44; 65-ARG--VAL-494 DEL; ALA-72; THR-82; THR-116; 155-GLN--VAL-494 DEL; ALA-175; ASP-217; THR-255; ARG-271; ILE-303; VAL-306; GLN-317; 356-TYR--VAL-494 DEL; CYS-367; TRP-393; SER-410; TRP-442; HIS-443 AND ARG-449; CHARACTERIZATION OF VARIANTS DEE84 VAL-44 AND THR-82; INVOLVEMENT IN DEE84; FUNCTION; CATALYTIC ACTIVITY; SUBUNIT;

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.