Evidence map›Paper›PMID 39928218›Full record

ArticleInternational journal of hematology2025

The novel protein C variant p.C101F results in early intracellular degradation that drives type I protein C deficiency.

Rikuto Yui, Satomi Nagaya, Ibuki Yasuda, Tomoki Togashi, Yuika Kikuchi, Kengo Saito, Makiko Meguro-Horike, Shin-Ichi Horike, Hiroshi Kawasaki, Hidekazu Nishikii and 1 more

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In one paragraph

Article in International journal of hematology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Rikuto Yui *Department of Laboratory Sciences, School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-0942, Japan.
Satomi Nagaya *Department of Clinical Laboratory Science, Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
Ibuki YasudaDepartment of Clinical Laboratory Science, Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
Tomoki TogashiDepartment of Clinical Laboratory Science, Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
Yuika KikuchiDepartment of Clinical Laboratory Science, Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
Kengo SaitoDepartment of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8640, Japan.
Makiko Meguro-HorikeResearch Center for Experimental Modeling of Human Disease, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8640, Japan.
Shin-Ichi HorikeResearch Center for Experimental Modeling of Human Disease, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8640, Japan.
Hiroshi KawasakiDepartment of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8640, Japan.
Hidekazu NishikiiDepartment of Hematology, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Eriko MorishitaDepartment of Clinical Laboratory Science, Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan. eriko86@staff.kanazawa-u.ac.jp.ORCID http://orcid.org/0000-0001-9116-3363

Funding

Japan Society for the Promotion of Science JP22K07391Japan Society for the Promotion of Science JP24K18661-00Ministry of Health, Labour and Welfare JPMH23FC1022
6 · The paper itself

Abstract

Hereditary protein C (PC) deficiency is an inherited thrombophilic disorder caused by variants in the PC gene (PROC). We identified a novel PROC variant, c.302G>T, p.Cys101Phe (C101F), in a patient with type I PC deficiency. We analyzed the intracellular dynamics of the C101F variant of PC (PC-C101F) to elucidate the pathogenic mechanism underlying this condition. Wild-type PC (PC-WT) and PC-C101F were transiently expressed in HEK293 cells for expression and functional analyses. The PC antigen levels in the cell lysate and culture supernatant of PC-C101F-expressing cells were significantly lower than those of PC-WT-expressing cells. In cycloheximide (CHX) chase experiments, the intracellular PC antigen level gradually decreased in PC-C101F-expressing cells, but remained stable at 0 and 6 h in the presence of CHX/MG132. No significant difference in co-localization with the endoplasmic reticulum was observed between PC-C101F and PC-WT. 101Cys forms a disulfide bond with 106Cys, which is crucial for maintaining the conformation of PC. PC-C101F likely results in protein misfolding and proteasomal degradation, leading to type I PC deficiency. These findings highlight the importance of cysteine residues in the three-dimensional structure of PC and provide insight into the mechanism of type I PC deficiency.

Indexed as

MutationProtein CProtein C DeficiencyProteolysisEndoplasmic ReticulumHEK293 CellsHumansProtein CArterial thromboembolismDisulfide bondMissense variantProteasomal degradationProtein C deficiency

Identifiers

PMID39928218

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.