MKRN1
Overview
MKRN1 (Makorin Ring Finger Protein 1) is an E3 ubiquitin ligase with roles in RNA metabolism and protein stability. In pilocytic astrocytoma (PA), MKRN1 has been identified as a novel 5’ fusion partner for BRAF, representing one of the alternative BRAF fusion events observed in tumors lacking the canonical KIAA1549:BRAF fusion. These BRAF fusions are the dominant oncogenic drivers in pilocytic astrocytoma.
Alterations observed in the corpus
- Identified as a novel 5’ fusion partner for BRAF in pilocytic astrocytoma; MKRN1:BRAF represents one of several alternative fusion events (alongside RNF130:BRAF, CLCN6:BRAF, GNAI1:BRAF) in tumors lacking the canonical KIAA1549:BRAF fusion PMID:23817572
- MKRN1/BRAF fusion detected in 1 of 13 BRAF-fusion cases (2.7% of tumors, n=484); MKRN1 acts as a novel BRAF fusion partner in PTC generating a kinase-domain-preserving structural variant PMID:25417114
Cancer types (linked)
- PA (pilocytic astrocytoma): BRAF fusion partner; functional dissection of the MKRN1:BRAF fusion (e.g., whether it activates MAPK signaling as potently as KIAA1549:BRAF) was not reported.
Co-occurrence and mutual exclusivity
- MKRN1:BRAF fusion is expected to be mutually exclusive with KIAA1549:BRAF (the dominant fusion in 70/96 cases) and with other BRAF-activating events in pilocytic astrocytoma PMID:23817572
Therapeutic relevance
- BRAF fusion tumors (including MKRN1:BRAF) are generally not candidates for V600E-selective BRAF inhibitors, which may cause paradoxical MAPK activation in fusion-driven tumors; MEK inhibition may be more appropriate PMID:23817572
Open questions
- Whether MKRN1:BRAF activates ERK phosphorylation equivalently to KIAA1549:BRAF (which has been shown to match BRAF V600E for ERK phosphorylation) has not been tested PMID:23817572
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:25417114
This page was processed by crosslinker on 2026-05-14.