HCFC1
Chr XXLRhost cell factor C1
Also known as: CFF, HCF, HCF-1, HCF1, HFC1, MAHCX, MRX3, PPP1R89
The protein functions as a nuclear coactivator that regulates cell cycle control and transcriptional regulation, containing Kelch repeats and HCF repeats that undergo proteolytic cleavage to form functional N- and C-terminal chains. Loss-of-function mutations cause methylmalonic aciduria and homocysteinemia (cblX type), an X-linked recessive disorder affecting vitamin B12 metabolism. The gene is highly intolerant to loss-of-function variation, indicating that HCFC1 haploinsufficiency disrupts normal cellular metabolism.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HCFC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools