Curated summary · agent-written · kb/genes/curated/hgnc_30220.md

All 14 claims checked against the KB draft

RFT1 across dismech

RFT1 (RFT1 glycolipid translocator homolog) is named by 1 disorder entry.

Normal function

ai-gene-review gives RFT1's core molecular function as intramembrane lipid transporter activity, moving Man5GlcNAc2-PP-dolichol from the cytoplasmic to the lumenal leaflet of the endoplasmic reticulum without ATP, acting in dolichol-linked oligosaccharide biosynthetic process; glycolipid translocation; and protein N-linked glycosylation at the endoplasmic reticulum membrane. GO has since renamed that molecular-function term to "intramembrane lipid carrier activity"; the identifier is unchanged.

Causative record

The one entry naming RFT1 types it as causative, RFT1-congenital disorder of glycosylation, with germline variants (RFT1-congenital disorder of glycosylation) whose functional impact is recorded as loss of function. ClinGen rates the relationship moderate. The gene sits on the node RFT1 Loss of Function.

Whether RFT1 is itself the flippase has been argued for two decades. The entry curates the flippase model and an essential-but-not-the-flippase model as competing hypotheses; a 2024 reconstitution of purified RFT1 supports the first.

Where the layers agree and disagree

ClinGen classifies RFT1 for 1 disease. The nodes naming RFT1 carry 0 process terms, so the KB and ai-gene-review share 0 GO process terms on it; the blocked lipid-linked oligosaccharide synthesis is recorded on the downstream node.

Underlined values are claims re-computed from the knowledge base each time this page is built. The tables below are the source of truth.

Normal function · from ai-gene-review (Q96AA3, commit 79fe13b38970) · AI-generated, not KB evidence

RFT1 encodes a polytopic endoplasmic reticulum membrane protein of the MOP (multidrug/oligosaccharidyl-lipid/polysaccharide) transporter superfamily that acts on Man(5)GlcNAc(2)-PP-dolichol (M5-DLO), the lipid-linked oligosaccharide intermediate of the N-glycosylation pathway. The protein spans the membrane roughly 12-14 times with both termini facing the cytosol, is not itself N-glycosylated, and is essential for viability in yeast and mammalian cells. Purified human RFT1 reconstituted into proteoliposomes translocates M5-DLO across the bilayer by an ATP-independent, bidirectional (scramblase-like) mechanism, with selectivity for the Man5 over shorter Man3 intermediates. Whether this translocase activity is the essential physiological role of the protein remains actively disputed: M5-DLO flipping persists in Rft1-depleted microsomes and in vesicles reconstituted with Rft1-free ER protein, Rft1-null Trypanosoma brucei is viable and glycosylates normally, and a yeast mutant engineered to block the lipid portal still supports robust growth, leading to an alternative model in which RFT1 acts as an M5-DLO chaperone that routes the intermediate for luminal completion. What is not in dispute is the pathway step at which the protein is required: loss of RFT1 function stalls dolichol-linked oligosaccharide assembly at M5-DLO and causes RFT1-CDG (CDG-In, OMIM 612015), a severe multisystem congenital disorder of glycosylation with neurodevelopmental abnormalities, hypotonia, epilepsy and sensorineural deafness.

ATP-independent intramembrane carrier for Man(5)GlcNAc(2)-PP-dolichol in the ER membrane. Purified human RFT1 reconstituted into liposomes moves M5GN2-PP-Dol across the bilayer without ATP and with selectivity for the Man5 over the Man3 intermediate, positioning the glycan head group for luminal elongation to the mature Glc3Man9GlcNAc2-PP-dolichol precursor. The activity is demonstrated; whether it is the essential physiological role of the protein is contested, so it is stated here at the level the reconstitution supports.

molecular function: intramembrane lipid transporter activity · directly involved in: glycolipid translocation; dolichol-linked oligosaccharide biosynthetic process; protein N-linked glycosylation · locations: endoplasmic reticulum membrane

Essential requirement for progression of dolichol-linked oligosaccharide assembly past the cytosolically oriented M5-DLO intermediate. Loss of RFT1 in yeast, in patient fibroblasts and in mammalian cells stalls the pathway at Man(5)GlcNAc(2)-PP-dolichol and hypoglycosylates secretory proteins, a defect rescued by wild-type cDNA. This requirement is agreed by both the transporter and the chaperone camps and is the claim the mutant-phenotype evidence actually licenses. No molecular_function is asserted for this entry, because the mutant-phenotype evidence establishes the pathway requirement without identifying the activity that satisfies it; the transport claim is stated separately above, at the level the reconstitution supports.

directly involved in: dolichol-linked oligosaccharide biosynthetic process; protein N-linked glycosylation · locations: endoplasmic reticulum membrane

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
RFT1-congenital disorder of glycosylation	causative germline loss of function CLINGEN: moderate	mechanism: RFT1 Loss of Function

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
RFT1-congenital disorder of glycosylation MONDO:0012783	AR	Moderate 2023-09-05	RFT1-congenital disorder of glycosylation causative