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UniProtKB/Swiss-Prot Q99714: Variant p.Arg130Cys

3-hydroxyacyl-CoA dehydrogenase type-2
Gene: HSD17B10
Variant information

Variant position:  130
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 Arginine (R) to Cysteine (C) at position 130 (R130C, p.Arg130Cys).
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 large size and basic (R) to medium size and polar (C)
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 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.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  130
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  261
The length of the canonical sequence.

Location on the sequence:   TLEDFQRVLDVNLMGTFNVI  R LVAGEMGQNEPDQGGQRGVI
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.

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.

TypePositionsDescription
Chain 2 – 261 3-hydroxyacyl-CoA dehydrogenase type-2
Helix 123 – 136


Literature citations

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;

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.