UniProtKB/SwissProt variant VAR

Hydroxymethylglutaryl-CoA lyase, mitochondrial
Gene: HMGCL
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Variant information Variant position:

233
Type of variant:

LP/P [Disclaimer]
Residue change:

From Histidine (H) to Arginine (R) at position 233 (H233R, p.His233Arg).
Physico-chemical properties:

Change from medium size and polar (H) to large size and basic (R)
BLOSUM score:

0
Variant description:

In HMGCLD; loss of activity.
Other resources:

Variant rs727503963 [ dbSNP | Ensembl ]

Sequence information Variant position:

233
Protein sequence length:

325
Location on the sequence:

IMKDMLSAVMQEVPLAALAV H CHDTYGQALANTLMALQMGV
Residue conservation:

Human                         IMKDMLSAVMQEVPLAALAVHCHDTYGQALANTLMALQMGV

Mouse                         LMKDMLTAVMHEVPVTALAVHCHDTYGQALANTLVALQMGV

Rat                           LMKDMLTAVLHEVPVAALAVHCHDTYGQALANTLVALQMGV

Bovine                        AMKDMLSAVLQEVPVTALAVHCHDTYGQALANTLTALQMGV

Chicken                       SMKEMLAAVMKEVPVGALAVHCHDTYGQALANILVALQMGV

Sequence annotation in neighborhood:

Type	Positions	Description
Chain	28 – 325	Hydroxymethylglutaryl-CoA lyase, mitochondrial
Domain	33 – 300	Pyruvate carboxyltransferase
Binding site	233 – 233
Binding site	235 – 235
Alternative sequence	188 – 250	Missing. In isoform 3.
Mutagenesis	233 – 233	H -> A. Loss of activity, and reduced proton exchange rate.
Beta strand	230 – 235

Literature citations
Modeling of a mutation responsible for human 3-hydroxy-3-methylglutaryl-CoA lyase deficiency implicates histidine-233 as an active site residue.
Roberts J.; Mitchell G.A.; Miziorko H.M.;
J. Biol. Chem. 271:24604-24609(1996)
Cited for: VARIANT HMGCLD ARG-233; Two missense point mutations in different alleles in the 3-hydroxy-3-methylglutaryl coenzyme A lyase gene produce 3-hydroxy-3-methylglutaric aciduria in a French patient.
Zapater N.; Pie J.; Lloberas J.; Rolland M.O.; Leroux B.; Vidailhet M.; Divry P.; Hegardt F.G.; Casals N.;
Arch. Biochem. Biophys. 358:197-203(1998)
Cited for: VARIANTS HMGCLD ARG-233 AND PRO-263; Ten novel HMGCL mutations in 24 patients of different origin with 3-hydroxy-3-methyl-glutaric aciduria.
Menao S.; Lopez-Vinas E.; Mir C.; Puisac B.; Gratacos E.; Arnedo M.; Carrasco P.; Moreno S.; Ramos M.; Gil M.C.; Pie A.; Ribes A.; Perez-Cerda C.; Ugarte M.; Clayton P.T.; Korman S.H.; Serra D.; Asins G.; Ramos F.J.; Gomez-Puertas P.; Hegardt F.G.; Casals N.; Pie J.;
Hum. Mutat. 30:E520-E529(2009)
Cited for: VARIANTS HMGCLD LYS-37; GLY-42; PHE-142; TYR-174; SER-192; PHE-200 AND ARG-233; CHARACTERIZATION OF VARIANTS HMGCLD LYS-37; PHE-142; TYR-174; SER-192 AND PHE-200;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35914: Variant p.His233Arg