Pyrroline-5-Carboxylate Reductase 1

Alternative Names

  • PYCR1
  • PRO3, Yeast, Human Complement of
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OMIM Number

179035

NCBI Gene ID

5831

Uniprot ID

P32322

Length

4,910 bases

No. of Exons

10

No. of isoforms

3

Protein Name

Pyrroline-5-carboxylate reductase 1, mitochondrial

Molecular Mass

33361 Da

Amino Acid Count

319

Genomic Location

chr17:81,932,390-81,937,299

Gene Map Locus
17q25.3

Description

PYCR1 gene encodes an enzyme that forms a homopolymer and localizes to the mitochondrion. The enzyme catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline and also plays a physiologic role in the generation of NADP(+) in some cell types. It has two transcript variants encoding different isoforms due to the alternate splicing of its encoding gene. Mutations in PYCR1 are the cause of cutis laxa autosomal recessive type 2B, characterized by abnormal growth, developmental delay, and associated skeletal abnormalities.

Epidemiology in the Arab World

View Map
Variant NameCountryGenomic LocationClinvar Clinical SignificanceCTGA Clinical Significance Condition(s)HGVS ExpressionsdbSNPClinvar
NM_006907.4:c.616G>ASaudi ArabiaNC_000017.11:g.81934670C>TLikely Pathogenic, PathogenicLikely PathogenicCutis Laxa, Autosomal Recessive, Type IIBNG_023032.1:g.7423G>A; NM_006907.4:c.616G>A; NP_008838.2:p.Gly206Arg12191837568789

Other Reports

Bahrain

Reversade et al. (2009) carried out mutation analysis for the PYCR1 gene in Bahraini patients affected with ARCL2. The c535G>A mutation was detected. The mutation is predicted to cause a p.A179T amino acid substitution in the resulting protein.

Iraq

[See: Syria > Dimopoulou et al., 2013].

Jordan

In affected members of a Jordanian family with intrauterine growth retardation, cutis laxa, hernias, abnormal corpus callosum, and mental retardation, and a Syrian patient with intrauterine growth retardation, cutis laxa, hernias, osteopenia, agenesis of the corpus callosum, and mental retardation, Reversade et al. (2009) identified homozygosity for a splice site deletion (797+2_797+5del) in intron 6 of the PYCR1 gene, predicted to result in K215_D319del. Analysis of skin fibroblasts from one of the affected Jordanian individuals revealed strongly reduced PYCR1 protein levels.

Kuwait

In three children with intrauterine growth retardation, cutis laxa, hip dislocation, hernias, osteopenia, and mental retardation from two unrelated consanguineous Kuwaiti families, Reversade et al. (2009) identified homozygosity for a 797G>A transition in exon 6 of the PYCR1 gene, resulting in an arg266-to-gln (p.R266Q) substitution predicted to affect splicing by altering the invariable donor splice site at the 3-prime end of exon 6.

Oman

In three sibs from a consanguineous Omani family with congenital cutis laxa, bowing of the long bones, multiple fractures due to osteopenia, and mental retardation, Reversade et al. (2009) identified homozygosity for a 356G>A transition in exon 4 of the PYCR1 gene, resulting in an arg119-to-his (p.R119H) substitution.

Palestine

In three Palestinian sibs with intrauterine growth retardation, cutis laxa, hip dislocation, osteopenia, mild abnormalities of the corpus callosum, and mild mental retardation, born of first-cousin parents, Reversade et al. (2009) identified homozygosity for a 22-bp deletion (617_633+6del) encompassing the exon-intron boundary of exon 5 of the PYCR1 gene. In a Palestinian girl, they have also identified homozygosity for a 616G>T transversion in exon 5 of the PYCR1 gene, resulting in a gly206-to-trp (p.G206W) substitution. Analysis of skin fibroblasts revealed a reduction in protein abundance relative to control cells.

Qatar

Reversade et al. (2009) reported a c.616G>A mutation in the PYCR1 gene in a Qatari family with ARCL2 disorder. The mutation is predicted to cause a p.G206R amino acid substitution in the resulting protein.

Saudi Arabia

Al-Owain et al. (2012) reported the case of a Saudi girl with De Barsy syndrome.  The patient was born full term to healthy consanguineous parents.  Sequencing of the PYCR1 gene revealed the presence of a homozygous missense mutation, c.616A>G, that results in a p.G206R substitution. 

Dimopoulou et al. (2013) described 33 patients with ARCL2, of which three were from Syria and one from Iraq. The Syrian patients were found to have homozygous splice site mutations at exon 4 of PYCR1 gene. The Iraqi patient had a homozygous p.Ala179Thr mutation at exon 4.

[See also: Jordan > Reversade et al., 2009].

Syria

Dimopoulou et al. (2013) described 33 patients with ARCL2, of which three were from Syria and one from Iraq. The Syrian patients were found to have homozygous splice site mutations at exon 4 of PYCR1 gene. The Iraqi patient had a homozygous p.Ala179Thr mutation at exon 4.

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