RFT1

Summary

RFT1 (RFT1 glycolipid translocator homolog, HGNC:30220) is a protein-coding gene on chromosome 3p21.1, encoding Man(5)GlcNAc(2)-PP-dolichol translocation protein RFT1 (Q96AA3). Intramembrane glycolipid transporter that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. It is a selective cancer dependency (DepMap: 82.9% of cell lines).

This gene encodes an enzyme which catalyzes the translocation of the Man(5)GlcNAc (2)-PP-Dol intermediate from the cytoplasmic to the luminal side of the endoplasmic reticulum membrane in the pathway for the N-glycosylation of proteins. Mutations in this gene are associated with congenital disorder of glycosylation type In.

Source: NCBI Gene 91869 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RFT1-congenital disorder of glycosylation (Strong, GenCC)
• GWAS associations: 26
• Clinical variants (ClinVar): 606 total — 5 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 82.9% of screened cell lines
• MANE Select transcript: NM_052859

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30220
Approved symbol	RFT1
Name	RFT1 glycolipid translocator homolog
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Aliases	CDG1N, SLC76A1
Ensembl gene	ENSG00000163933
Ensembl biotype	protein_coding
OMIM	611908
Entrez	91869

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000296292, ENST00000394738, ENST00000467048, ENST00000471158, ENST00000850556, ENST00000909794, ENST00000909795, ENST00000909796, ENST00000909797, ENST00000968202, ENST00000968203

RefSeq mRNA: 1 — MANE Select: NM_052859 NM_052859

CCDS: CCDS2869

Canonical transcript exons

ENST00000296292 — 13 exons

Exon	Start	End
ENSE00001079768	53123724	53123840
ENSE00001079770	53121699	53121800
ENSE00001079771	53103953	53104097
ENSE00001079773	53088483	53092070
ENSE00001079775	53092369	53092618
ENSE00001079776	53125909	53125994
ENSE00001079778	53122374	53122563
ENSE00001079780	53099381	53099486
ENSE00001906545	53130338	53130435
ENSE00003527248	53105673	53105803
ENSE00003533348	53111830	53111908
ENSE00003635305	53106819	53106869
ENSE00003640205	53119884	53120021

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 86.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2030 / max 75.9185, expressed in 1802 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42500	17.2030	1802

Top tissues by expression

240 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.97	gold quality
body of pancreas	UBERON:0001150	86.60	gold quality
islet of Langerhans	UBERON:0000006	86.31	gold quality
stromal cell of endometrium	CL:0002255	86.04	gold quality
pancreas	UBERON:0001264	85.38	gold quality
vermiform appendix	UBERON:0001154	84.60	gold quality
right adrenal gland	UBERON:0001233	84.01	gold quality
rectum	UBERON:0001052	83.81	gold quality
left adrenal gland	UBERON:0001234	83.70	gold quality
leukocyte	CL:0000738	83.68	gold quality
monocyte	CL:0000576	83.66	gold quality
smooth muscle tissue	UBERON:0001135	83.37	gold quality
calcaneal tendon	UBERON:0003701	83.20	gold quality
mucosa of transverse colon	UBERON:0004991	83.07	gold quality
right adrenal gland cortex	UBERON:0035827	82.99	gold quality
left adrenal gland cortex	UBERON:0035825	82.90	gold quality
ventricular zone	UBERON:0003053	82.79	gold quality
gall bladder	UBERON:0002110	82.62	gold quality
adrenal gland	UBERON:0002369	82.53	gold quality
adrenal tissue	UBERON:0018303	82.17	gold quality
esophagus mucosa	UBERON:0002469	81.71	gold quality
granulocyte	CL:0000094	81.46	gold quality
lymph node	UBERON:0000029	81.43	gold quality
adrenal cortex	UBERON:0001235	81.35	gold quality
right ovary	UBERON:0002118	81.26	gold quality
body of stomach	UBERON:0001161	81.04	gold quality
left ovary	UBERON:0002119	80.95	gold quality
bone marrow cell	CL:0002092	80.65	gold quality
left coronary artery	UBERON:0001626	80.63	gold quality
oviduct epithelium	UBERON:0004804	80.55	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.12
E-GEOD-124858	no	73.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting RFT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1273H-5P	99.77	66.32	2471

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 82.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• RFT1 deficiency in both yeast and human cells leads to the accumulation of incomplete DolPP-GlcNAc(2)Man(5) and to a profound glycosylation disorder in humans. (PMID:18313027)
• Six patients with RFT1-CDG show sensorineural deafness as part of a severe neurological syndrome (PMID:19856127)
• Identification of novel missense mutations in exon 12 of the RFT1 gene in adult siblings with congenital disorder of glycosylation (CDG) syndrome caused by RFT1 deficiency. (PMID:23111317)
• showed that this patient was compound heterozygous for two mutations in the RFT1 gene: c.1325G>A (p.R442Q) and c.110G>T (p.R37L) (PMID:26892341)
• A novel RFT1 missense mutation was identified in a family with history of neonatal deaths due to severe respiratory insufficiency. (PMID:30071302)
• Molecular characterization of Rft1, an ER membrane protein associated with congenital disorder of glycosylation RFT1-CDG. (PMID:39025454)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rft1	ENSDARG00000060398
mus_musculus	Rft1	ENSMUSG00000052395
rattus_norvegicus	Rft1	ENSRNOG00000021805
drosophila_melanogaster	CG3149	FBGN0027564
caenorhabditis_elegans		WBGENE00022677

Protein

Protein identifiers

Man(5)GlcNAc(2)-PP-dolichol translocation protein RFT1 — Q96AA3 (reviewed: Q96AA3)

Alternative names: Protein RFT1 homolog

All UniProt accessions (3): B5MDE0, C9JP01, Q96AA3

UniProt curated annotations — full annotation on UniProt →

Function. Intramembrane glycolipid transporter that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The sequential addition of sugars to dolichol pyrophosphate produces dolichol-linked oligosaccharides containing fourteen sugars, including two GlcNAcs, nine mannoses and three glucoses. Once assembled, the oligosaccharide is transferred from the lipid to nascent proteins by oligosaccharyltransferases. The assembly of dolichol-linked oligosaccharides begins on the cytosolic side of the endoplasmic reticulum membrane and finishes in its lumen. RFT1 could mediate the translocation of the cytosolically oriented intermediate DolPP-GlcNAc2Man5, produced by ALG11, into the ER lumen where dolichol-linked oligosaccharides assembly continues. However, the intramembrane lipid transporter activity could not be confirmed in vitro.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Congenital disorder of glycosylation 1N (CDG1N) [MIM:612015] A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the RFT1 family.

RefSeq proteins (1): NP_443091* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007594	RFT1	Family

Pfam: PF04506

UniProt features (17 total): transmembrane region 12, sequence variant 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AA3-F1	90.46	0.75

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-4570571	Defective RFT1 causes CDG-1n

MSigDB gene sets: 155 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, KEGG_N_GLYCAN_BIOSYNTHESIS, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, NKX62_Q2, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, OCT1_03, FISCHER_DREAM_TARGETS, GOBP_MEMBRANE_ORGANIZATION, GOBP_LIPID_LOCALIZATION, GOBP_CARBOHYDRATE_DERIVATIVE_TRANSPORT, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, CGTSACG_PAX3_B

GO Biological Process (3): protein N-linked glycosylation (GO:0006487), dolichol-linked oligosaccharide biosynthetic process (GO:0006488), glycolipid translocation (GO:0034203)

GO Molecular Function (2): glycolipid floppase activity (GO:0034202), protein binding (GO:0005515)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Asparagine N-linked glycosylation	1
Diseases associated with N-glycosylation of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycoprotein biosynthetic process	1
protein N-linked glycosylation	1
carbohydrate derivative biosynthetic process	1
lipid translocation	1
glycolipid transport	1
glycolipid translocation	1
floppase activity	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

466 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFT1	ALG11	Q2TAA5	951
RFT1	PMM2	O15305	777
RFT1	TOR3A	Q9H497	625
RFT1	ZNF704	Q6ZNC4	563
RFT1	ZNF668	Q96K58	480
RFT1	RBPMS	Q93062	453
RFT1	MRPS18A	Q9NVS2	452
RFT1	RASL11B	Q9BPW5	431
RFT1	SPAG4	Q9NPE6	400
RFT1	RTF1	Q92541	379
RFT1	GGA2	Q9UJY4	372
RFT1	DAAM2	Q86T65	369
RFT1	LRRCC1	Q9C099	367
RFT1	ALG2	Q9H553	353
RFT1	RBM28	Q9NW13	350
RFT1	ACP6	Q9NPH0	350

IntAct

99 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
AQP6	RFT1	psi-mi:“MI:0915”(physical association)	0.560
CNR2	RFT1	psi-mi:“MI:0915”(physical association)	0.560
RFT1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
RFT1	TMX2	psi-mi:“MI:0915”(physical association)	0.560
MUC1	RFT1	psi-mi:“MI:0915”(physical association)	0.560
BEST2	RFT1	psi-mi:“MI:0915”(physical association)	0.560
RNF144A	RFT1	psi-mi:“MI:0915”(physical association)	0.560
TSPAN12	RFT1	psi-mi:“MI:0915”(physical association)	0.560
RFT1	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
LYPD3	CLASP2	psi-mi:“MI:0914”(association)	0.350
	SLC19A2	psi-mi:“MI:0914”(association)	0.350
	NBAS	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
	SURF4	psi-mi:“MI:0914”(association)	0.350
M	TM9SF1	psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (120): RFT1 (Two-hybrid), RFT1 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), RFT1 (Affinity Capture-MS), RFT1 (Two-hybrid), RFT1 (Proximity Label-MS), RFT1 (Proximity Label-MS)

ESM2 similar proteins: A3KNK1, C7T2J9, D2HBV9, O19133, O88788, O95427, P35575, P35576, P43428, Q19KA1, Q1LZA0, Q1LZE6, Q29RU6, Q3T1L5, Q3TAE8, Q3U3R4, Q3UGP8, Q3ZBF8, Q4V7R2, Q5BKT4, Q5E9R6, Q5I7T1, Q5RJM1, Q61907, Q6DE21, Q6DHU1, Q6ZMG9, Q7SXZ1, Q802T2, Q8BMD6, Q8C172, Q8C3B8, Q8K2A8, Q8N5B7, Q8TCT8, Q8WUD6, Q924Z4, Q92521, Q92685, Q92903

Diamond homologs: Q0D2E8, Q23444, Q8C3B8, Q96AA3, Q9Y123

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
R-HSA-425366	5	15.6×	1e-03
Class A/1 (Rhodopsin-like receptors)	10	12.8×	1e-06
GPCR ligand binding	8	8.8×	3e-04
SLC-mediated transmembrane transport	7	7.1×	2e-03
Signaling by GPCR	8	5.5×	3e-03
Transport of small molecules	12	5.2×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	6	15.4×	1e-03
sodium ion transmembrane transport	5	11.9×	9e-03
positive regulation of cytosolic calcium ion concentration	6	8.3×	9e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	6	8.0×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

606 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	9
Uncertain significance	278
Likely benign	203
Benign	59

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
207987	NM_052859.4(RFT1):c.892G>A (p.Glu298Lys)	Pathogenic
207988	NM_052859.4(RFT1):c.887T>A (p.Ile296Lys)	Pathogenic
207989	NM_052859.4(RFT1):c.887T>G (p.Ile296Arg)	Pathogenic
207990	NM_052859.4(RFT1):c.1222A>G (p.Met408Val)	Pathogenic
807671	NM_052859.4(RFT1):c.775G>A (p.Gly259Ser)	Pathogenic
1350291	NM_052859.4(RFT1):c.1195G>T (p.Glu399Ter)	Likely pathogenic
207991	NM_052859.4(RFT1):c.1325G>A (p.Arg442Gln)	Likely pathogenic
2572513	NM_052859.4(RFT1):c.229C>T (p.Arg77Ter)	Likely pathogenic
3254892	NM_052859.4(RFT1):c.1208+1G>T	Likely pathogenic
3393040	NM_052859.4(RFT1):c.306G>A (p.Trp102Ter)	Likely pathogenic
3572861	NM_052859.4(RFT1):c.775+1G>C	Likely pathogenic
426331	NM_052859.4(RFT1):c.545del (p.Phe182fs)	Likely pathogenic
495320	NM_052859.4(RFT1):c.902A>G (p.Tyr301Cys)	Likely pathogenic
931309	NM_052859.4(RFT1):c.740dup (p.Lys248fs)	Likely pathogenic

SpliceAI

1854 predictions. Top by Δscore:

Variant	Effect	Δscore
3:53104105:C:CT	acceptor_gain	1.0000
3:53104105:C:T	acceptor_gain	1.0000
3:53104106:A:T	acceptor_gain	1.0000
3:53105799:CACAC:C	acceptor_gain	1.0000
3:53105801:CAC:C	acceptor_gain	1.0000
3:53105805:T:C	acceptor_loss	1.0000
3:53106817:AC:A	donor_gain	1.0000
3:53106818:CC:C	donor_gain	1.0000
3:53106870:C:CC	acceptor_gain	1.0000
3:53111825:CTTA:C	donor_loss	1.0000
3:53111826:TTACC:T	donor_loss	1.0000
3:53111827:TACC:T	donor_loss	1.0000
3:53111829:C:A	donor_loss	1.0000
3:53111829:CCTT:C	donor_gain	1.0000
3:53111906:CGC:C	acceptor_gain	1.0000
3:53122369:CTGA:C	donor_loss	1.0000
3:53122370:TGA:T	donor_loss	1.0000
3:53122371:GAC:G	donor_loss	1.0000
3:53122373:C:CA	donor_loss	1.0000
3:53122562:CT:C	acceptor_gain	1.0000
3:53122562:CTCT:C	acceptor_loss	1.0000
3:53122563:TCTAG:T	acceptor_loss	1.0000
3:53122564:C:CC	acceptor_gain	1.0000
3:53122564:C:T	acceptor_loss	1.0000
3:53123722:A:AC	donor_gain	1.0000
3:53123723:C:CC	donor_gain	1.0000
3:53125992:CAC:C	acceptor_gain	1.0000
3:53125992:CACCT:C	acceptor_loss	1.0000
3:53125995:CTAT:C	acceptor_loss	1.0000
3:53125996:T:C	acceptor_loss	1.0000

AlphaMissense

3462 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:53111846:T:A	K253N	0.997
3:53111846:T:G	K253N	0.997
3:53105761:C:G	R290T	0.995
3:53111830:C:G	G259R	0.995
3:53105760:T:A	R290S	0.994
3:53105760:T:G	R290S	0.994
3:53111847:T:A	K253I	0.994
3:53111848:T:C	K253E	0.994
3:53121786:G:C	S157R	0.994
3:53121786:G:T	S157R	0.994
3:53121788:T:G	S157R	0.994
3:53105777:C:G	G285R	0.993
3:53122520:A:G	W104R	0.993
3:53122520:A:T	W104R	0.993
3:53123832:A:G	L53P	0.993
3:53123838:A:G	L51P	0.993
3:53125925:C:G	G45R	0.993
3:53092522:G:C	N435K	0.992
3:53092522:G:T	N435K	0.992
3:53092539:C:G	G430R	0.992
3:53105761:C:A	R290I	0.992
3:53106869:C:T	G259D	0.992
3:53125924:C:T	G45D	0.992
3:53105764:G:T	A289D	0.991
3:53105776:C:T	G285D	0.991
3:53106819:C:G	G276R	0.991
3:53092535:A:G	F431S	0.990
3:53099434:A:C	N385K	0.989
3:53099434:A:T	N385K	0.989
3:53105774:A:G	S286P	0.989

dbSNP variants (sampled 300 via entrez): RS1000003653 (3:53096146 T>C), RS1000050396 (3:53117506 C>T), RS1000100949 (3:53068401 C>G), RS1000132373 (3:53116448 C>G,T), RS1000177143 (3:53119993 C>T), RS1000223349 (3:53105393 G>A), RS1000252504 (3:53119561 G>A), RS1000345676 (3:53099039 A>C), RS1000367512 (3:53066390 G>T), RS1000371491 (3:53073113 G>A), RS1000425319 (3:53072719 G>A), RS1000465442 (3:53092747 T>G), RS1000470412 (3:53113320 T>C), RS1000552998 (3:53091561 T>C), RS1000577316 (3:53105789 C>T)

Disease associations

OMIM: gene MIM:611908 | disease phenotypes: MIM:612015

GenCC curated gene-disease

Disease	Classification	Inheritance
RFT1-congenital disorder of glycosylation	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
RFT1-congenital disorder of glycosylation	Moderate	AR

Mondo (1): RFT1-congenital disorder of glycosylation (MONDO:0012783)

Orphanet (1): RFT1-CDG (Orphanet:244310)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000470	Short neck
HP:0000505	Visual impairment
HP:0000932	Abnormal posterior cranial fossa morphology
HP:0001181	Adducted thumb
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0001892	Abnormal bleeding
HP:0001928	Abnormality of coagulation
HP:0001977	Abnormal thrombosis
HP:0002059	Cerebral atrophy
HP:0002093	Respiratory insufficiency
HP:0002120	Cerebral cortical atrophy
HP:0002240	Hepatomegaly
HP:0002401	Stroke-like episode
HP:0002783	Recurrent lower respiratory tract infections
HP:0002804	Arthrogryposis multiplex congenita
HP:0003186	Inverted nipples
HP:0003256	Abnormality of the coagulation cascade
HP:0003593	Infantile onset

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST001241_15	Bipolar disorder	2.000000e-06
GCST001535_13	Immune reponse to smallpox (secreted IL-2)	3.000000e-11
GCST001956_66	Height	2.000000e-12
GCST002149_14	Schizophrenia	1.000000e-08
GCST004067_126	Hip circumference adjusted for BMI	1.000000e-11
GCST004067_14	Hip circumference adjusted for BMI	6.000000e-14
GCST004067_209	Hip circumference adjusted for BMI	4.000000e-06
GCST004132_28	Crohn’s disease	7.000000e-09
GCST004521_203	Autism spectrum disorder or schizophrenia	4.000000e-08
GCST004521_259	Autism spectrum disorder or schizophrenia	6.000000e-09
GCST005983_44	Serum uric acid levels	4.000000e-09
GCST006950_62	Feeling worry	3.000000e-14
GCST007725_29	Serum uric acid levels	3.000000e-12
GCST007733_42	Serum uric acid levels	5.000000e-18
GCST007733_54	Serum uric acid levels	9.000000e-12
GCST008839_19	Height	1.000000e-16
GCST009379_250	Type 2 diabetes	2.000000e-08
GCST010658_4	High density lipoprotein cholesterol levels	1.000000e-08
GCST011686_2	Diastolic blood pressure	3.000000e-07
GCST90020024_1217	A body shape index	3.000000e-10
GCST90020025_1348	Waist-to-hip ratio adjusted for BMI	2.000000e-13
GCST90020025_1351	Waist-to-hip ratio adjusted for BMI	5.000000e-08
GCST90020027_148	Waist-hip index	2.000000e-08
GCST90020027_149	Waist-hip index	6.000000e-13
GCST90020028_799	Hip circumference adjusted for BMI	5.000000e-15
GCST90020029_1202	Waist circumference adjusted for body mass index	6.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004761	uric acid measurement
EFO:0009589	worry measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006336	diastolic blood pressure
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567437	Congenital Disorder Of Glycosylation, Type In (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067273 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.95	Kd	1126	nM	CHEMBL3752910
5.95	ED50	1126	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149222: Binding affinity to human RFT1 incubated for 45 mins by Kinobead based pull down assay	kd	1.1261	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
monomethylarsonous acid	increases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Endosulfan	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Ketoconazole	decreases expression	1
Malathion	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652264	Binding	Binding affinity to human RFT1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.