Variant position:  130

Type of variant:  LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.]

Residue change:  From Arginine (R) to Cysteine (C) at position 130 (R130C, p.Arg130Cys).

Physico-chemical properties:  Change from large size and basic (R) to medium size and polar (C)

BLOSUM score:  -3

Variant description:  In HSD10MD; decreased stability; decreased 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity; decreased mitochondrial tRNA 5'-end processing; decreased tRNA methylation; does not affect homotetramerization; complete loss of phospholipase C-like activity toward cardiolipin.

Other resources:  

• Variant rs28935475 [ dbSNP | Ensembl ]

Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases.
Boynton T.O.; Shimkets L.J.;
Genes Dev. 29:1903-1914(2015)
Cited for: FUNCTION; ACTIVITY REGULATION; BIOPHYSICOCHEMICAL PROPERTIES; VARIANTS HSD10MD GLY-86; CYS-130 AND HIS-165;

A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival.
Rauschenberger K.; Schoeler K.; Sass J.O.; Sauer S.; Djuric Z.; Rumig C.; Wolf N.I.; Okun J.G.; Koelker S.; Schwarz H.; Fischer C.; Grziwa B.; Runz H.; Nuemann A.; Shafqat N.; Kavanagh K.L.; Haemmerling G.; Wanders R.J.; Shield J.P.; Wendel U.; Stern D.; Nawroth P.; Hoffmann G.F.; Bartram C.R.; Arnold B.; Bierhaus A.; Oppermann U.; Steinbeisser H.; Zschocke J.;
EMBO Mol. Med. 2:51-62(2010)
Cited for: X-RAY CRYSTALLOGRAPHY (1.20 ANGSTROMS); FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; VARIANTS HSD10MD GLY-86; CYS-130 AND HIS-165; CHARACTERIZATION OF VARIANTS HSD10MD GLY-86; CYS-130 AND HIS-165;

2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene.
Ofman R.; Ruiter J.P.N.; Feenstra M.; Duran M.; Poll-The B.T.; Zschocke J.; Ensenauer R.; Lehnert W.; Sass J.O.; Sperl W.; Wanders R.J.A.;
Am. J. Hum. Genet. 72:1300-1307(2003)
Cited for: VARIANTS HSD10MD VAL-122 AND CYS-130;

2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease.
Perez-Cerda C.; Garcia-Villoria J.; Ofman R.; Sala P.R.; Merinero B.; Ramos J.; Garcia-Silva M.T.; Beseler B.; Dalmau J.; Wanders R.J.A.; Ugarte M.; Ribes A.;
Pediatr. Res. 58:488-491(2005)
Cited for: VARIANTS HSD10MD CYS-130 AND SER-247; CHARACTERIZATION OF VARIANT HSD10MD SER-247;

Study of patients and carriers with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: difficulties in the diagnosis.
Garcia-Villoria J.; Navarro-Sastre A.; Fons C.; Perez-Cerda C.; Baldellou A.; Fuentes-Castello M.A.; Gonzalez I.; Hernandez-Gonzalez A.; Fernandez C.; Campistol J.; Delpiccolo C.; Cortes N.; Messeguer A.; Briones P.; Ribes A.;
Clin. Biochem. 42:27-33(2009)
Cited for: VARIANTS HSD10MD CYS-130; SER-210; GLN-226 AND SER-247; FUNCTION; CATALYTIC ACTIVITY;

Mental retardation linked to mutations in the HSD17B10 gene interfering with neurosteroid and isoleucine metabolism.
Yang S.Y.; He X.Y.; Olpin S.E.; Sutton V.R.; McMenamin J.; Philipp M.; Denman R.B.; Malik M.;
Proc. Natl. Acad. Sci. U.S.A. 106:14820-14824(2009)
Cited for: VARIANTS HSD10MD CYS-130 AND GLN-249; CHARACTERIZATION OF VARIANTS HSD10MD CYS-130 AND GLN-249; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; PATHWAY;

Mutation or knock-down of 17beta-hydroxysteroid dehydrogenase type 10 cause loss of MRPP1 and impaired processing of mitochondrial heavy strand transcripts.
Deutschmann A.J.; Amberger A.; Zavadil C.; Steinbeisser H.; Mayr J.A.; Feichtinger R.G.; Oerum S.; Yue W.W.; Zschocke J.;
Hum. Mol. Genet. 23:3618-3628(2014)
Cited for: VARIANTS HSD10MD CYS-130 AND HIS-165; CHARACTERIZATION OF VARIANT HSD10MD CYS-130; FUNCTION;

Molecular insights into HSD10 disease: impact of SDR5C1 mutations on the human mitochondrial RNase P complex.
Vilardo E.; Rossmanith W.;
Nucleic Acids Res. 43:5112-5119(2015)
Cited for: VARIANTS HSD10MD CYS-130; SER-210; GLN-226 AND SER-247; FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; MUTAGENESIS OF LYS-172; CHARACTERIZATION OF VARIANTS HSD10MD CYS-130; SER-210; GLN-226 AND SER-247;