Reduced protein C activity: genes and variants

Reduced protein C activity is linked to 1 analyzed protein (PROC). 12 DNA variants are known to cause it; 9 more are uncertain, and 0 of those already look disease-causing on computable evidence.

Last updated 2026-09-30. Research information, not medical advice.

Genes linked to Reduced protein C activity

PROC: Vitamin K-dependent protein C
After activation, protein C limits coagulation by proteolytically inactivating factors Va and VIIIa with protein S as a cofactor. Heterozygous deficiency increases venous-thrombosis risk, while severe biallelic deficiency can cause neonatal purpura fulminans.
12 disease-causing and 9 uncertain variants in PROC are linked to Reduced protein C activity.

Where Reduced protein C activity variants cluster

PROC EGF-like 2 (positions 136–176): 3 of 12 disease-causing changes, 2.8× more than its size predicts.

Known disease-causing variants in Reduced protein C activity

Variant	Position	Protein part	Clinical label
PROC C147Y	147	EGF-like 2	Disease-causing (★★)
PROC R328C	328	Peptidase S1	Disease-causing (★★)
PROC D401N	401	Peptidase S1	Disease-causing (★★)
PROC A178P	178		Disease-causing (★★)
PROC R211W	211		Disease-causing (★★)
PROC D393N	393	Peptidase S1	Disease-causing (★★)
PROC V26M	26		Disease-causing (★)
PROC S141P	141	EGF-like 2	Disease-causing (★)
PROC T340K	340	Peptidase S1	Disease-causing (★)
PROC H253Q	253	Peptidase S1	Disease-causing
PROC D170Y	170	EGF-like 2	Disease-causing
PROC A251E	251	Peptidase S1	Disease-causing

Same protein, different disease

Thrombophilia due to protein C deficiency, autosomal dominant is also caused by PROC variants; they fall mostly in different places as the Reduced protein C activity variants (50 disease-causing).
Deep venous thrombosis is also caused by PROC variants; they fall mostly in different places as the Reduced protein C activity variants (5 disease-causing).
Hereditary thrombophilia due to congenital protein C deficiency is also caused by PROC variants; they fall mostly in different places as the Reduced protein C activity variants (3 disease-causing).

Diseases related to Reduced protein C activity

Thrombophilia due to protein C deficiency, autosomal dominant, also linked to PROC
Deep venous thrombosis, also linked to PROC
Hereditary thrombophilia due to congenital protein C deficiency, also linked to PROC

Frequently asked questions

Which genes are linked to Reduced protein C activity?

In CATVariant, Reduced protein C activity is linked to 1 analyzed protein: PROC (Vitamin K-dependent protein C).

How many genetic variants are linked to Reduced protein C activity?

21 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 9 are of uncertain significance or have conflicting reports.

Which uncertain variants in Reduced protein C activity look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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