IFITM3

Summary

IFITM3 (interferon induced transmembrane protein 3, HGNC:5414) is a protein-coding gene on chromosome 11p15.5, encoding Interferon-induced transmembrane protein 3 (Q01628). IFN-induced antiviral protein which disrupts intracellular cholesterol homeostasis. It is a common-essential gene (DepMap: required in 96.0% of cancer cell lines).

Interferon-induced transmembrane (IFITM) proteins are a family of interferon induced antiviral proteins. The family contains five members, including IFITM1, IFITM2 and IFITM3 and belong to the CD225 superfamily. The protein encoded by this gene restricts cellular entry by diverse viral pathogens, such as influenza A virus, Ebola virus and Sars-CoV-2.

Source: NCBI Gene 10410 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 27 total
• Cancer dependency (DepMap): dependent in 96.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_021034

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5414
Approved symbol	IFITM3
Name	interferon induced transmembrane protein 3
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	1-8U, DSPA2b
Ensembl gene	ENSG00000142089
Ensembl biotype	protein_coding
OMIM	605579
Entrez	10410

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 16 protein_coding, 8 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay, 1 non_stop_decay

ENST00000399808, ENST00000526811, ENST00000531688, ENST00000602735, ENST00000602809, ENST00000602949, ENST00000679382, ENST00000679433, ENST00000679441, ENST00000679746, ENST00000679792, ENST00000679793, ENST00000679830, ENST00000680023, ENST00000680209, ENST00000680372, ENST00000680622, ENST00000680716, ENST00000680720, ENST00000680920, ENST00000680932, ENST00000681048, ENST00000681184, ENST00000681198, ENST00000681304, ENST00000681748, ENST00000681840, ENST00000926220

RefSeq mRNA: 1 — MANE Select: NM_021034 NM_021034

CCDS: CCDS41585

Canonical transcript exons

ENST00000399808 — 2 exons

Exon	Start	End
ENSE00001540252	319676	319990
ENSE00001540254	320565	320860

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 327.2703 / max 4098.1008, expressed in 1748 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117740	306.4394	1726
206072	11.2851	1510
117739	8.3940	1457
206071	1.0647	593
117741	0.0452	6
117744	0.0419	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left uterine tube	UBERON:0001303	99.92	gold quality
left coronary artery	UBERON:0001626	99.90	gold quality
descending thoracic aorta	UBERON:0002345	99.90	gold quality
pericardium	UBERON:0002407	99.90	gold quality
ascending aorta	UBERON:0001496	99.89	gold quality
thoracic aorta	UBERON:0001515	99.89	gold quality
coronary artery	UBERON:0001621	99.89	gold quality
upper lobe of left lung	UBERON:0008952	99.89	gold quality
right coronary artery	UBERON:0001625	99.88	gold quality
peritoneum	UBERON:0002358	99.87	gold quality
upper lobe of lung	UBERON:0008948	99.87	gold quality
omental fat pad	UBERON:0010414	99.87	gold quality
metanephros cortex	UBERON:0010533	99.87	gold quality
endocervix	UBERON:0000458	99.86	gold quality
right lung	UBERON:0002167	99.85	gold quality
body of uterus	UBERON:0009853	99.85	gold quality
lower esophagus	UBERON:0013473	99.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.85	gold quality
aorta	UBERON:0000947	99.84	gold quality
apex of heart	UBERON:0002098	99.84	gold quality
mucosa of stomach	UBERON:0001199	99.83	gold quality
tibial nerve	UBERON:0001323	99.83	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.83	gold quality
right lobe of thyroid gland	UBERON:0001119	99.82	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.82	gold quality
right lobe of liver	UBERON:0001114	99.81	gold quality
right ovary	UBERON:0002118	99.81	gold quality
left lobe of thyroid gland	UBERON:0001120	99.80	gold quality
right uterine tube	UBERON:0001302	99.80	gold quality
popliteal artery	UBERON:0002250	99.80	gold quality

Single-cell (SCXA)

Detected in 74 experiment(s), a significant marker in 64.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	8413.71
E-HCAD-24	yes	6935.11
E-CURD-55	yes	6009.25
E-CURD-88	yes	5925.57
E-MTAB-6701	yes	5870.64
E-MTAB-6308	yes	5434.78
E-GEOD-149689	yes	5415.99
E-HCAD-1	yes	5224.32
E-CURD-122	yes	4781.17
E-HCAD-4	yes	4749.92
E-MTAB-8142	yes	4726.91
E-MTAB-9435	yes	4649.14
E-MTAB-6653	yes	4382.34
E-MTAB-10287	yes	3841.07
E-GEOD-134144	yes	3808.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF4, SIN3A, SP1, STAT1, TEAD1

miRNA regulators (miRDB)

9 targeting IFITM3, 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-3176	99.25	64.35	954
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-4654	95.86	65.72	751
HSA-MIR-4769-5P	95.37	66.09	570
HSA-MIR-3679-5P	94.75	66.46	862
HSA-MIR-1185-5P	94.47	65.95	725

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• regulation of IFITM3 by TEF-1 demonstrates that TEF-1 dependent regulation is more widespread than its previously established role in the expression of muscle specific genes (PMID:18177740)
• IFITM3 plays an important role in early colon cancer development (PMID:18470904)
• This work has shown for the first time that IFITM3 physically interacts with OPN and reduces OPN mRNA expression (PMID:19901966)
• gene polymorphism is associated with susceptibility to ulcerative colitis in Korean population (PMID:19946179)
• IFITM2 and IFITM3, disrupted early steps (entry and/or uncoating) of the viral infection, viperin, ISG20, and double-stranded-RNA-activated protein kinase, inhibited steps in west nile virus and dengue virus viral proteins and/or RNA biosynthesis. (PMID:20534863)
• IFITM1, IFITM2, and IFITM3 inhibit HIV-1 replication through interfering with virus entry. (PMID:21177806)
• promoter demethylation enhances transcriptional response to IFN-alpha treatment in melanoma cells (PMID:21413873)
• IFITM3 was expressed at higher levels in colon tumors and, particularly, nodal metastases than in normal colon tissue. (PMID:21531817)
• To further investigate the 1-8U function with both in vivo and in vitro studies, the 1-8U gene was found to suppress cellular and hepatitis C virus internal ribosomal entry site-mediated translation. (PMID:21914072)
• data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans (PMID:22446628)
• S-palmitoylation and ubiquitination differentially regulate interferon-induced transmembrane protein 3 (IFITM3)-mediated resistance to influenza virus. (PMID:22511783)
• the CC genotype of ITITM3 is found in 69% of Chinese patients with severe pandemic influenza A H1N1/09 virus infection compared with 25% in those with mild infection. (PMID:23361009)
• Although their inhibitory activities were modest when compared to that of tetherin, IFITMs, but not tetherin, directly reduced the expression of HIV-1 proteins including Gag, Vif and Nef. (PMID:23376165)
• The antiviral effector protein interferon-inducible transmembrane protein 3 (IFITM3) interacts with VAPA and prevents its association with OSBP. (PMID:23601107)
• IFITM3 protein was highly expressed in invasive breast cancer compared to normal tissues and was significantly associated with estrogen receptor and progesterone receptor status. (PMID:23624618)
• IFITM3 restricts infection by a nonenveloped virus. (PMID:23649619)
• The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza A virus and dengue virus replication. (PMID:23658454)
• Authors show that interferon-induced transmembrane protein 1 (IFITM-1), IFITM-2, and IFITM-3 exhibit a broad spectrum of antiviral activity against several members of the Bunyaviridae family. (PMID:23720721)
• rs3888188, a functional promoter polymorphism of IFITM3, was identified to influence the risk for pediatric TB in Han Chinese population. (PMID:23874452)
• Authors found evidence of an association between rs12252 rare allele homozygotes and susceptibility to mild influenza (in patients attending primary care). (PMID:23997235)
• Vesicular stomatitis virus and influenza A virus increased IFITM3-K88me1 levels by promoting the interaction between IFITM3 and SET7, suggesting that this pathway could be hijacked to support infection; conversely, IFN-alpha reduced IFITM3-K88me1 levels. (PMID:24129573)
• The IFITM3 genotype is a primary driver of the observed differences in clinical outcome after H7N9 infection. (PMID:24367104)
• The findings of this study provided new evidence that IFITM3 plays an important role in glioma cell growth and migration. (PMID:24370119)
• As an endocytic protein, IFITM3 first arrives at the plasma membrane before it is endocytosed and further traffics to the late endosomes where it acts to impede virus entry. (PMID:24521078)
• IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes. (PMID:24699674)
• Exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content. resulting in a decrease in influenza replication. (PMID:24978204)
• Taken together, these data suggested that IFITM3 is a potential therapeutic target for GC. (PMID:25270246)
• Tyrosine 20 partially regulates the subcellular localization of IFITM3 but is not functionally essential for IFITM3-mediated H1N1 restriction. (PMID:25314048)
• Authors suggest that IFITM3 adopts multiple membrane topologies involving at least one intramembrane domain in its antivirally active conformation. (PMID:25405885)
• In virus-producing cells, IFITMs coalesce with forming virions and are incorporated into HIV-1 viral particles. (PMID:25422070)
• Incorporation of IFITM1, IFITM2 and IFITM3 into HIV-1 virions impair viral fusion and spread. (PMID:25464829)
• Host IFITM3,IFITM2 and IFITM1 facilitate morphogenesis of the human cytomegalovirus assembly. (PMID:25552713)
• This meta-analysis suggests that IFITM3 rs12252 T>C polymorphism is significantly associated with increased risk of severe influenza but not with the chance of initial virus infection. (PMID:25778715)
• A novel association between IFITM3 gene polymorphism and rapid disease progression is reported in an acute HIV-1-infected MSM cohort in China. (PMID:25784441)
• Our meta-analysis suggests a significant association between a minor IFITM3 allele (SNP rs12252-C) with severe influenza susceptibility, but not in mild influenza subjects (PMID:25942469)
• we demonstrate that the E3 ubiquitin ligase NEDD4 ubiquitinates IFITM3 in cells and in vitro. (PMID:26263374)
• propose that the IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation and demonstrate that the actions of the IFITM proteins are indeed virus and cell-type specific (PMID:26354436)
• IFITM2 and IFITM3 specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. (PMID:26387945)
• there is one transmembrane helix in the human IFITM3 with a possible role in virus entry (PMID:27046158)
• These results indicate that IFITM3 protein can restrict alphavirus infection by inhibiting viral fusion with cellular membranes. (PMID:27219333)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ifitm1	ENSMUSG00000025491
mus_musculus	Ifitm3	ENSMUSG00000025492
mus_musculus	Ifitm2	ENSMUSG00000060591
mus_musculus	Ifitm7	ENSMUSG00000065968
rattus_norvegicus	Ifitm1	ENSRNOG00000004273
rattus_norvegicus	Ifitm3-ps2	ENSRNOG00000021674
rattus_norvegicus		ENSRNOG00000080209

Paralogs (5): IFITM2 (ENSG00000185201), IFITM1 (ENSG00000185885), IFITM5 (ENSG00000206013), IFITM10 (ENSG00000244242), (ENSG00000300510)

Protein

Protein identifiers

Interferon-induced transmembrane protein 3 — Q01628 (reviewed: Q01628)

Alternative names: Dispanin subfamily A member 2b, Interferon-inducible protein 1-8U

All UniProt accessions (9): Q01628, A0A7P0T8W2, A0A7P0T9S7, A0A7P0T9U8, A0A7P0TB46, A0A7P0TB91, A0A7P0TBF9, E9PS44, R4GNG9

UniProt curated annotations — full annotation on UniProt →

Function. IFN-induced antiviral protein which disrupts intracellular cholesterol homeostasis. Inhibits the entry of viruses to the host cell cytoplasm by preventing viral fusion with cholesterol depleted endosomes. May inactivate new enveloped viruses which buds out of the infected cell, by letting them go out with a cholesterol depleted membrane. Active against multiple viruses, including influenza A virus, SARS coronaviruses (SARS-CoV and SARS-CoV-2), Marburg virus (MARV), Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV) and vesicular stomatitis virus (VSV). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry, SARS-CoV and SARS-CoV-2 S protein-mediated viral entry and VSV G protein-mediated viral entry. Plays a critical role in the structural stability and function of vacuolar ATPase (v-ATPase). Establishes physical contact with the v-ATPase of endosomes which is critical for proper clathrin localization and is also required for the function of the v-ATPase to lower the pH in phagocytic endosomes thus establishing an antiviral state. In hepatocytes, IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation. IFITM2 and IFITM3 display anti-HCV activity that may complement the anti-HCV activity of IFITM1 by inhibiting the late stages of HCV entry, possibly in a coordinated manner by trapping the virion in the endosomal pathway and targeting it for degradation at the lysosome. Exerts opposing activities on SARS-CoV-2, including amphipathicity-dependent restriction of virus at endosomes and amphipathicity-independent enhancement of infection at the plasma membrane.

Subunit / interactions. Interacts with ATP6V0B. Interacts with CD81. Interacts with SPP1; the interaction reduces OPN expression. Interacts with VAPA. Interacts with BRI3 (isoforms 1 and 2); the interaction with isoform 2 is weaker than with isoform 1.

Subcellular location. Cell membrane. Late endosome membrane. Early endosome membrane. Lysosome membrane. Cytoplasm. Perinuclear region.

Post-translational modifications. Palmitoylation on membrane-proximal cysteines controls clustering in membrane compartments and antiviral activity against influenza virus and hepatitis C virus (HCV). Has no effect on anti-SARS-CoV-2 activity. Not glycosylated. Polyubiquitinated with both ‘Lys-48’ and ‘Lys-63’ linkages. Ubiquitination negatively regulates antiviral activity. Lys-24 is the most prevalent ubiquitination site. Phosphorylation at Tyr-20 is required for endosomal and lysosomal location.

Induction. By IFN-alpha and IFNG/IFN-gamma.

Polymorphism. Genetic variations in IFITM3 are responsible for susceptibility to severe influenza virus infection [MIM:614680].

Similarity. Belongs to the CD225/Dispanin family.

RefSeq proteins (1): NP_066362* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007593	CD225/Dispanin_fam	Family
IPR051517	IFITM_antiviral_protein	Family

Pfam: PF04505

UniProt features (25 total): mutagenesis site 6, cross-link 4, topological domain 3, lipid moiety-binding region 3, sequence conflict 2, region of interest 2, chain 1, sequence variant 1, intramembrane region 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01628-F1	59.40	0.00

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 (8): 72, 105, 24, 83, 88, 104, 20, 71

Mutagenesis-validated functional residues (6):

Position	Phenotype
20	loss of phosphorylation. accumulates at the plasma membrane. increases anti-hcv properties. loss of anti-sars-cov-2 acti
23	accumulates at the plasma membrane. loss of anti-sars-cov-2 activity by enhancing spike-mediated cell-to-cell fusion.
59–68	slightly enhances infection by sars-cov-2.
61–65	decreases anti-sars-cov-2 activity.
71–72	loss of anti-hcv activity. only localizes at the lysosome. no effect on sars-cov-2 infection; when associated with a-105
105	loss of anti-hcv activity. only localizes at the lysosome. no effect on sars-cov-2 infection; when associated with 71-a-

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-909733	Interferon alpha/beta signaling

MSigDB gene sets: 445 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_RESPONSE_TO_PEPTIDE, GOCC_VACUOLAR_MEMBRANE, BECKER_TAMOXIFEN_RESISTANCE_UP, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, MODULE_128, HSIAO_HOUSEKEEPING_GENES, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, DARWICHE_PAPILLOMA_RISK_HIGH_UP

GO Biological Process (12): immune response (GO:0006955), response to virus (GO:0009615), negative regulation of viral transcription (GO:0032897), response to type II interferon (GO:0034341), response to interferon-alpha (GO:0035455), response to interferon-beta (GO:0035456), negative regulation of viral genome replication (GO:0045071), host-mediated suppression of symbiont invasion (GO:0046597), defense response to virus (GO:0051607), type I interferon-mediated signaling pathway (GO:0060337), immune system process (GO:0002376), innate immune response (GO:0045087)

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

GO Cellular Component (10): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), protein-containing complex (GO:0032991), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to cytokine	3
cellular anatomical structure	3
negative regulation of viral process	2
innate immune response	2
endosome membrane	2
immune system process	1
response to stimulus	1
response to other organism	1
viral transcription	1
regulation of viral transcription	1
viral genome replication	1
regulation of viral genome replication	1
host-mediated perturbation of symbiont process	1
defense response	1
response to virus	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
biological_process	1
immune response	1
defense response to symbiont	1
binding	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
early endosome	1
late endosome	1
cellular_component	1
cytoplasm	1
intracellular anatomical structure	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

2050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFITM3	IFIT3	O14879	876
IFITM3	VAPA	Q9P0L0	838
IFITM3	IFIT1	P09914	817
IFITM3	MX1	P20591	808
IFITM3	ISG15	P05161	807
IFITM3	IFI6	P09912	779
IFITM3	IFIT2	P09913	770
IFITM3	IFI44L	Q53G44	757
IFITM3	OAS1	P00973	757
IFITM3	IFI44	Q8TCB0	756
IFITM3	IFNB1	P01574	749
IFITM3	OASL	Q15646	745
IFITM3	IFI27	P40305	730
IFITM3	B3GNT3	Q9Y2A9	728
IFITM3	IFI35	P80217	721

IntAct

132 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
IFITM3	REEP4	psi-mi:“MI:0915”(physical association)	0.670
IFITM3	RETREG3	psi-mi:“MI:0915”(physical association)	0.670
IFITM3	SLC16A7	psi-mi:“MI:0915”(physical association)	0.560
OPRM1	IFITM3	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
KIR2DL3	IFITM3	psi-mi:“MI:0915”(physical association)	0.560
SLC16A7	IFITM3	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	IFITM3	psi-mi:“MI:0915”(physical association)	0.560
SGPL1	IFITM3	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	ELOVL2	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	FKBP7	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	GPRC5D	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	LYPD5	psi-mi:“MI:0915”(physical association)	0.560
PLP1	IFITM3	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
FFAR2	IFITM3	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	MS4A3	psi-mi:“MI:0915”(physical association)	0.560
CD53	IFITM3	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	AQP6	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	SLC10A2	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	FAM210B	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	TMEM86B	psi-mi:“MI:0915”(physical association)	0.560
BRI3	IFITM3	psi-mi:“MI:0915”(physical association)	0.540
BRI3	IFITM3	psi-mi:“MI:0403”(colocalization)	0.540

BioGRID (603): FYN (Affinity Capture-Western), IFITM3 (Two-hybrid), IFITM3 (Affinity Capture-Western), NEDD4 (Affinity Capture-Western), IFITM3 (Biochemical Activity), IFITM3 (PCA), IFITM3 (Affinity Capture-MS), IFITM3 (Affinity Capture-MS), IFITM3 (Affinity Capture-MS), ALDH3A2 (Affinity Capture-MS), ARF4 (Affinity Capture-MS), ATP1A1 (Affinity Capture-MS), ATP1B3 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5B (Affinity Capture-MS)

ESM2 similar proteins: A0A087WTH1, A0A125YWU9, A0PK84, A6PVL3, C9JQL5, F1QHM7, F1QX91, O15503, O41933, O70418, O88728, P0DI73, P13164, P26376, Q01628, Q01629, Q08755, Q0II74, Q21642, Q32L65, Q3UNB8, Q3YBM2, Q5FVR1, Q5FWL7, Q5I0I2, Q5R8D6, Q5RF75, Q5Y5T3, Q6DHI1, Q76IC6, Q7M734, Q7TQJ1, Q8BGI3, Q8CES1, Q8CFA6, Q8IYP9, Q8N6L7, Q8WVZ1, Q91WU6, Q921C1

Diamond homologs: A6NMD0, A6NNB3, C9JQL5, O88728, P13164, P26376, Q01628, Q01629, Q8BR26, Q91499, Q99J93, Q9CQW9, Q9D103, D3ZFB6, E9PUL5, Q2MHH0, Q5RAC1, Q6DFT4, Q7Z6L0, Q8C838

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IFITM3	“up-regulates activity”	gamma-secretase	binding
FYN	“up-regulates quantity”	IFITM3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

192 predictions. Top by Δscore:

Variant	Effect	Δscore
11:320561:GCAC:G	donor_loss	1.0000
11:320562:CA:C	donor_loss	1.0000
11:320563:A:AC	donor_gain	1.0000
11:320563:AC:A	donor_gain	1.0000
11:320564:C:CC	donor_gain	1.0000
11:320564:CC:C	donor_gain	1.0000
11:320564:CCTT:C	donor_gain	1.0000
11:319989:GA:G	acceptor_gain	0.9900
11:319991:C:CC	acceptor_gain	0.9900
11:319991:C:CG	acceptor_loss	0.9900
11:319992:T:C	acceptor_loss	0.9900
11:320560:CGCA:C	donor_gain	0.9900
11:320563:ACCTT:A	donor_gain	0.9900
11:320564:CCTTC:C	donor_gain	0.9900
11:319986:CTAGA:C	acceptor_gain	0.9800
11:319988:AGA:A	acceptor_gain	0.9700
11:320564:CCT:C	donor_gain	0.9700
11:319987:TAGA:T	acceptor_gain	0.9600
11:320905:T:A	donor_gain	0.9300
11:319982:GTCC:G	acceptor_gain	0.9200
11:320560:CG:C	donor_gain	0.9200
11:320871:C:A	donor_gain	0.8700
11:320876:T:A	donor_gain	0.8500
11:320911:T:A	donor_gain	0.8500
11:320127:T:A	donor_gain	0.8300
11:320562:CACCT:C	donor_gain	0.8200
11:320561:GCACC:G	donor_gain	0.8100
11:319984:CC:C	acceptor_gain	0.8000
11:319985:CC:C	acceptor_gain	0.8000
11:320249:C:CC	acceptor_gain	0.8000

AlphaMissense

873 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:319985:C:A	R85S	0.993
11:319985:C:G	R85S	0.993
11:319986:C:A	R85M	0.993
11:319919:G:C	N107K	0.992
11:319919:G:T	N107K	0.992
11:320636:A:G	W60R	0.991
11:320636:A:T	W60R	0.991
11:319986:C:G	R85T	0.990
11:320565:C:A	K83N	0.990
11:320565:C:G	K83N	0.990
11:320594:C:G	G74R	0.990
11:320622:G:C	N64K	0.990
11:320622:G:T	N64K	0.990
11:319983:T:A	D86V	0.989
11:319983:T:G	D86A	0.989
11:319984:C:G	D86H	0.989
11:319932:G:T	A103D	0.986
11:319933:C:G	A103P	0.985
11:320584:G:T	A77E	0.985
11:320593:C:T	G74D	0.984
11:320607:G:C	N69K	0.984
11:320607:G:T	N69K	0.984
11:319968:C:A	G91V	0.983
11:319976:C:A	K88N	0.983
11:319976:C:G	K88N	0.983
11:320572:G:A	S81F	0.982
11:319923:A:G	L106P	0.980
11:319953:G:T	A96D	0.980
11:320641:A:T	V58D	0.980
11:319989:G:A	S84F	0.979

dbSNP variants (sampled 300 via entrez): RS1001130177 (11:322623 G>A,C,T), RS1004126462 (11:320445 A>G), RS1004310280 (11:320120 C>T), RS1005062381 (11:322835 G>A), RS1010394813 (11:322596 C>G), RS1010981048 (11:320008 G>A), RS1015677598 (11:320452 C>T), RS1019296394 (11:320929 C>A,G,T), RS1021528686 (11:320968 C>T), RS1031474238 (11:319650 C>G), RS1033683420 (11:321102 G>A,C), RS1037975941 (11:319605 C>A), RS1041092862 (11:321263 C>T), RS1042599976 (11:322609 C>T), RS1049596244 (11:321238 G>A,C,T)

Disease associations

OMIM: gene MIM:605579 | disease phenotypes: MIM:614680

GenCC curated gene-disease

Mondo (1): influenza, severe, susceptibility to (MONDO:0013855)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004600_95	Eosinophil percentage of white cells	6.000000e-13
GCST004617_135	Eosinophil percentage of granulocytes	2.000000e-13
GCST004623_50	Neutrophil percentage of granulocytes	1.000000e-11
GCST009597_74	Multiple sclerosis	1.000000e-08
GCST90002381_291	Eosinophil count	2.000000e-37
GCST90002382_376	Eosinophil percentage of white cells	9.000000e-45

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0004842	eosinophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12252	IFITM3		0.00	0

CTD chemical–gene interactions

69 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance	4
Valproic Acid	decreases expression, increases expression, increases methylation	4
sodium arsenite	decreases expression, increases expression	3
Particulate Matter	increases reaction, decreases expression, increases abundance, affects expression	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
epigallocatechin gallate	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
lead acetate	decreases expression	1
methylparaben	decreases expression	1
sulforaphane	decreases expression	1
sulindac sulfide	decreases expression	1
ochratoxin A	increases acetylation, increases expression	1
cupric chloride	decreases expression	1
lei gong teng	decreases expression	1
azoxystrobin	decreases expression	1
chloropicrin	decreases expression	1
deguelin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
candoxin	decreases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
ICG 001	increases expression	1

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B0A4	HeLa IFITM1/2/3-KO	Cancer cell line	Female
CVCL_B0A5	HeLa IFITM2/3-KO	Cancer cell line	Female
CVCL_B0A6	A549 IFITM2/3-KO	Cancer cell line	Male
CVCL_B1U8	Abcam HeLa IFITM3 KO	Cancer cell line	Female
CVCL_SS21	HAP1 IFITM3 (-) 1	Cancer cell line	Male
CVCL_SS22	HAP1 IFITM3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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