RFTN2

Summary

RFTN2 (raftlin family member 2, HGNC:26402) is a protein-coding gene on chromosome 2q33.1, encoding Raftlin-2 (Q52LD8). Upon bacterial lipopolysaccharide stimulation, mediates clathrin-dependent internalization of TLR4 in dendritic cells, resulting in activation of TICAM1-mediated signaling and subsequent IFNB1 production.

Predicted to act upstream of or within dsRNA transport and response to exogenous dsRNA. Predicted to be located in plasma membrane.

Source: NCBI Gene 130132 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_144629

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26402
Approved symbol	RFTN2
Name	raftlin family member 2
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30574, Raftlin-2
Ensembl gene	ENSG00000162944
Ensembl biotype	protein_coding
OMIM	618215
Entrez	130132

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000295049, ENST00000429081, ENST00000454447, ENST00000494346, ENST00000870691, ENST00000870692, ENST00000870693

RefSeq mRNA: 1 — MANE Select: NM_144629 NM_144629

CCDS: CCDS2323

Canonical transcript exons

ENST00000295049 — 9 exons

Exon	Start	End
ENSE00001070066	197631011	197631220
ENSE00001070067	197617800	197617921
ENSE00001070069	197644158	197644272
ENSE00001070071	197633718	197633997
ENSE00001181051	197646483	197646666
ENSE00001181057	197675320	197675587
ENSE00001283014	197568224	197572280
ENSE00003494496	197595991	197596069
ENSE00003546663	197615876	197615979

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 94.65.

FANTOM5 (CAGE): breadth broad, TPM avg 11.5925 / max 5318.8670, expressed in 846 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33091	6.4901	673
33096	2.5331	505
33092	2.0631	442
33093	0.1934	77
33095	0.1617	74
33090	0.1167	56
33094	0.0343	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	94.65	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.58	gold quality
medial globus pallidus	UBERON:0002477	91.41	gold quality
spinal cord	UBERON:0002240	91.40	gold quality
corpus callosum	UBERON:0002336	91.00	gold quality
calcaneal tendon	UBERON:0003701	90.19	gold quality
tendon of biceps brachii	UBERON:0008188	89.36	gold quality
globus pallidus	UBERON:0001875	87.52	gold quality
amygdala	UBERON:0001876	87.38	gold quality
tendon	UBERON:0000043	87.24	gold quality
caudate nucleus	UBERON:0001873	87.01	gold quality
substantia nigra	UBERON:0002038	86.91	gold quality
embryo	UBERON:0000922	86.86	gold quality
ganglionic eminence	UBERON:0004023	86.86	gold quality
adrenal tissue	UBERON:0018303	86.22	gold quality
sural nerve	UBERON:0015488	86.11	gold quality
putamen	UBERON:0001874	85.97	gold quality
stromal cell of endometrium	CL:0002255	85.62	gold quality
hypothalamus	UBERON:0001898	85.52	gold quality
tibia	UBERON:0000979	85.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.04	gold quality
nucleus accumbens	UBERON:0001882	84.85	gold quality
midbrain	UBERON:0001891	84.71	gold quality
anterior cingulate cortex	UBERON:0009835	84.66	gold quality
prefrontal cortex	UBERON:0000451	84.24	gold quality
right frontal lobe	UBERON:0002810	83.94	gold quality
Ammon’s horn	UBERON:0001954	83.04	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.44	gold quality
tibial nerve	UBERON:0001323	82.34	gold quality
neocortex	UBERON:0001950	81.59	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	23.74
E-ANND-3	yes	9.78
E-GEOD-93593	yes	4.43
E-ENAD-17	no	631.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting RFTN2, 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-126-5P	100.00	72.71	3180
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rftn2	ENSDARG00000056078
mus_musculus	Rftn2	ENSMUSG00000025978
rattus_norvegicus	Rftn2	ENSRNOG00000015594

Paralogs (1): RFTN1 (ENSG00000131378)

Protein

Protein identifiers

Raftlin-2 — Q52LD8 (reviewed: Q52LD8)

Alternative names: Raft-linking protein 2

All UniProt accessions (3): C9J6C2, Q52LD8, H7BZ31

UniProt curated annotations — full annotation on UniProt →

Function. Upon bacterial lipopolysaccharide stimulation, mediates clathrin-dependent internalization of TLR4 in dendritic cells, resulting in activation of TICAM1-mediated signaling and subsequent IFNB1 production. May regulate B-cell antigen receptor-mediated signaling.

Subcellular location. Cell membrane.

Similarity. Belongs to the raftlin family.

RefSeq proteins (1): NP_653230* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028169	Raftlin	Family

Pfam: PF15250

UniProt features (14 total): modified residue 3, region of interest 3, compositionally biased region 3, lipid moiety-binding region 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q52LD8-F1	69.19	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 430, 2, 3, 405, 409

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, FOXD3_01, NFKB_C, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, HFH8_01, TGIF_01, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, OCT1_07, HFH3_01, HFH1_01, AACTTT_UNKNOWN, GOBP_RESPONSE_TO_DSRNA, SOX5_01, GOBP_RNA_LOCALIZATION, NERF_Q2

GO Biological Process (2): dsRNA transport (GO:0033227), response to exogenous dsRNA (GO:0043330)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA transport	1
response to dsRNA	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFTN2	ARL6IP6	Q8N6S5	552
RFTN2	PLCL1	Q15111	490
RFTN2	PLBD2	Q8NHP8	489
RFTN2	HEMK2	Q9Y5N5	488
RFTN2	ANKRD44	Q8N8A2	479
RFTN2	NUGGC	Q68CJ6	450
RFTN2	MOSPD2	Q8NHP6	449
RFTN2	OTOP1	Q7RTM1	420
RFTN2	Q3MI93	Q3MI93	417
RFTN2	FKBP9	O95302	398
RFTN2	AKAP14	Q86UN6	376
RFTN2	CAMSAP2	Q08AD1	373
RFTN2	BOLL	Q8N9W6	372
RFTN2	LYSMD1	Q96S90	370
RFTN2	PLXDC2	Q6UX71	359

IntAct

8 interactions, top by confidence:

A	B	Type	Score
RFTN2	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
RFTN2	NMT1	psi-mi:“MI:0914”(association)	0.350
TNNI2	NUCB2	psi-mi:“MI:0914”(association)	0.350
RFTN2	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
TNNI2	UBE2M	psi-mi:“MI:0914”(association)	0.350
RFTN2	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): POMT2 (Affinity Capture-MS), RFTN2 (Affinity Capture-MS), RABGAP1L (Affinity Capture-MS), POMT1 (Affinity Capture-MS), CCDC88A (Affinity Capture-MS), USP30 (Affinity Capture-MS), NMT1 (Affinity Capture-MS), RFTN2 (Two-hybrid), CCDC88A (Affinity Capture-MS), POMT1 (Affinity Capture-MS), USP30 (Affinity Capture-MS), RABGAP1L (Affinity Capture-MS), RFTN2 (Affinity Capture-MS), NMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M3AJY3, A6QLR3, A7E379, B5X1P9, D3IUT5, D3ZSP7, E2AB17, O00443, O88196, P53804, P59438, Q08D12, Q0JF48, Q0VA42, Q0VF22, Q15018, Q1LVP6, Q28HX0, Q2T9I9, Q3TCJ1, Q4R9E9, Q52LD8, Q5E9P1, Q5I0F1, Q5R458, Q5RA75, Q5RAY1, Q5RFV8, Q5TEA3, Q5XJY6, Q5ZHS0, Q5ZKI7, Q60MF5, Q61194, Q6DDJ5, Q6GR31, Q6P4W0, Q6PUR7, Q6UWZ7, Q8BPZ8

Diamond homologs: Q14699, Q52LD8, Q5R458, Q6A0D4, Q7SZI5, Q8CHX7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1882 predictions. Top by Δscore:

Variant	Effect	Δscore
2:197572039:T:TA	donor_gain	1.0000
2:197595990:CAT:C	donor_gain	1.0000
2:197596065:CTTCA:C	acceptor_gain	1.0000
2:197596066:TTCA:T	acceptor_gain	1.0000
2:197596067:TCA:T	acceptor_gain	1.0000
2:197596068:CA:C	acceptor_gain	1.0000
2:197596068:CAC:C	acceptor_gain	1.0000
2:197596068:CACTG:C	acceptor_loss	1.0000
2:197596069:AC:A	acceptor_loss	1.0000
2:197596070:C:CC	acceptor_gain	1.0000
2:197596070:CT:C	acceptor_loss	1.0000
2:197615870:CCTTA:C	donor_loss	1.0000
2:197615871:CTTA:C	donor_loss	1.0000
2:197615872:TTA:T	donor_loss	1.0000
2:197615874:A:AG	donor_loss	1.0000
2:197617794:GCTCA:G	donor_loss	1.0000
2:197617795:CTCA:C	donor_loss	1.0000
2:197617796:TCACC:T	donor_loss	1.0000
2:197617797:CACCT:C	donor_loss	1.0000
2:197617798:A:AC	donor_gain	1.0000
2:197617798:A:T	donor_loss	1.0000
2:197617799:C:CC	donor_gain	1.0000
2:197617799:CCT:C	donor_gain	1.0000
2:197617919:CCC:C	acceptor_gain	1.0000
2:197617920:CC:C	acceptor_gain	1.0000
2:197617920:CCC:C	acceptor_gain	1.0000
2:197617920:CCCTG:C	acceptor_loss	1.0000
2:197617921:CC:C	acceptor_gain	1.0000
2:197617922:C:A	acceptor_loss	1.0000
2:197617922:C:CC	acceptor_gain	1.0000

AlphaMissense

3279 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:197615922:A:G	W370R	0.999
2:197615922:A:T	W370R	0.999
2:197631089:A:G	W284R	0.998
2:197631089:A:T	W284R	0.998
2:197675384:T:A	R25S	0.997
2:197675384:T:G	R25S	0.997
2:197596027:C:A	R399S	0.996
2:197596027:C:G	R399S	0.996
2:197615920:C:A	W370C	0.996
2:197615920:C:G	W370C	0.996
2:197615926:G:C	F368L	0.996
2:197615926:G:T	F368L	0.996
2:197615928:A:G	F368L	0.996
2:197675385:C:G	R25T	0.996
2:197675403:A:T	I19K	0.996
2:197596028:C:G	R399T	0.995
2:197617828:A:T	I341N	0.995
2:197675391:A:G	L23P	0.995
2:197675403:A:G	I19T	0.995
2:197596034:A:G	L397P	0.994
2:197596048:C:A	K392N	0.994
2:197596048:C:G	K392N	0.994
2:197617814:A:G	W346R	0.994
2:197617814:A:T	W346R	0.994
2:197675452:A:G	C3R	0.994
2:197615921:C:G	W370S	0.993
2:197615924:C:A	G369V	0.993
2:197615936:A:G	L365P	0.992
2:197675397:G:A	S21F	0.992
2:197675445:A:T	L5H	0.992

dbSNP variants (sampled 300 via entrez): RS1000007782 (2:197672788 G>A), RS1000015357 (2:197656058 A>G), RS1000021693 (2:197604280 A>G), RS1000046082 (2:197654011 T>C), RS1000060977 (2:197660715 C>T), RS1000077213 (2:197610430 T>C), RS1000087136 (2:197571080 T>C), RS1000140642 (2:197629617 A>T), RS1000163890 (2:197627823 T>TA), RS1000244531 (2:197675019 C>T), RS1000252286 (2:197585623 T>C), RS1000294342 (2:197598181 G>A), RS1000324826 (2:197675897 C>A,T), RS1000340092 (2:197573964 G>C), RS1000341037 (2:197591458 G>A)

Disease associations

OMIM: gene MIM:618215 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001728_23	Ulcerative colitis	3.000000e-08
GCST002539_41	Schizophrenia	2.000000e-11
GCST004132_35	Crohn’s disease	7.000000e-08
GCST004521_180	Autism spectrum disorder or schizophrenia	3.000000e-11
GCST004521_275	Autism spectrum disorder or schizophrenia	7.000000e-09
GCST005588_15	Idiopathic dilated cardiomyopathy	7.000000e-06
GCST006803_21	Schizophrenia	4.000000e-13
GCST007293_117	Body fat distribution (arm fat ratio)	1.000000e-06
GCST007293_18	Body fat distribution (arm fat ratio)	2.000000e-07
GCST007293_44	Body fat distribution (arm fat ratio)	8.000000e-11
GCST007294_108	Body fat distribution (trunk fat ratio)	4.000000e-06
GCST007294_27	Body fat distribution (trunk fat ratio)	3.000000e-09
GCST007565_136	Morning person	6.000000e-23
GCST010698_25	Subcortical volume (min-P)	2.000000e-08
GCST010699_24	Brain morphology (min-P)	1.000000e-09
GCST010700_25	Cortical thickness (MOSTest)	2.000000e-10
GCST010701_25	Cortical surface area (MOSTest)	2.000000e-37
GCST010702_65	Subcortical volume (MOSTest)	1.000000e-11
GCST010703_197	Brain morphology (MOSTest)	1.000000e-11
GCST011176_21	Stroke	8.000000e-07
GCST90002403_106	Red blood cell count	8.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0004341	body fat distribution
EFO:0008328	chronotype measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
trichostatin A	affects cotreatment, increases expression	3
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
Benzo(a)pyrene	affects methylation	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Triclosan	increases expression	1
Levonorgestrel	increases expression, affects cotreatment	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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