C1QBP – Mitochondrial Disease

C1QBP encodes complementary C1q-binding protein (p32), a mitochondrial matrix protein essential for oxidative phosphorylation. A homozygous c.823C>T (p.Leu275Phe) variant in C1QBP was identified in two Chinese siblings presenting with exercise intolerance and ptosis, leading to early-onset combined oxidative phosphorylation deficiency under an autosomal recessive inheritance mode (PMID:33344382). Parents were heterozygous carriers without clinical manifestations, supporting segregation.

Functional studies of HABP1 (p32) truncating variants in COS-1 cells demonstrated that disruption of trimeric assembly induces autophagic vacuolation and F-actin disassembly, underscoring p32’s role in mitochondrial homeostasis and stress responses (PMID:15005653). A recent review consolidates C1QBP deficiency phenotypes—including mitochondrial cardiomyopathy, external ophthalmoplegia, and combined oxidative phosphorylation defects—observed in autosomal recessive cases, confirming loss-of-function as a disease mechanism (PMID:35310974).

Key Take-home: Biallelic loss-of-function variants in C1QBP cause autosomal recessive mitochondrial disease, guiding targeted genetic diagnosis and management of combined OXPHOS deficiencies.

References

• Frontiers in Pediatrics • 2020 • Early Onset of Combined Oxidative Phosphorylation Deficiency in Two Chinese Brothers Caused by a Homozygous (Leu275Phe) Mutation in the C1QBP Gene PMID:33344382
• The Biochemical Journal • 2004 • Truncated variants of hyaluronan-binding protein 1 bind hyaluronan and induce identical morphological aberrations in COS-1 cells PMID:15005653
• Frontiers in Cardiovascular Medicine • 2022 • Complement C1q Binding Protein (C1QBP): Physiological Functions, Mutation-Associated Mitochondrial Cardiomyopathy and Current Disease Models PMID:35310974

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