IFI44

Summary

IFI44 (interferon induced protein 44, HGNC:16938) is a protein-coding gene on chromosome 1p31.1, encoding Interferon-induced protein 44 (Q8TCB0). This protein aggregates to form microtubular structures.

Predicted to be involved in immune response. Predicted to act upstream of or within cellular response to virus and response to bacterium. Predicted to be located in cytoplasm.

Source: NCBI Gene 10561 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_006417

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16938
Approved symbol	IFI44
Name	interferon induced protein 44
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	MTAP44, p44, TLDC5
Ensembl gene	ENSG00000137965
Ensembl biotype	protein_coding
OMIM	610468
Entrez	10561

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 5 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000370747, ENST00000438486, ENST00000446486, ENST00000467790, ENST00000470323, ENST00000472152, ENST00000476911, ENST00000485662, ENST00000495254, ENST00000879045, ENST00000879046, ENST00000879047, ENST00000879048, ENST00000879049

RefSeq mRNA: 1 — MANE Select: NM_006417 NM_006417

CCDS: CCDS688

Canonical transcript exons

ENST00000370747 — 9 exons

Exon	Start	End
ENSE00001932223	78649831	78649905
ENSE00003475271	78650186	78650652
ENSE00003544750	78655014	78655209
ENSE00003558415	78654243	78654279
ENSE00003559609	78655362	78655511
ENSE00003610985	78662704	78662878
ENSE00003631529	78659312	78659483
ENSE00003686263	78660554	78660654
ENSE00003844551	78663765	78664073

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 97.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.5139 / max 1526.8265, expressed in 1418 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3681	37.0836	1417
3682	0.4304	150

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.70	gold quality
mononuclear cell	CL:0000842	97.46	gold quality
leukocyte	CL:0000738	97.24	gold quality
gall bladder	UBERON:0002110	97.18	gold quality
spleen	UBERON:0002106	97.03	gold quality
calcaneal tendon	UBERON:0003701	95.87	gold quality
granulocyte	CL:0000094	95.82	gold quality
apex of heart	UBERON:0002098	95.80	gold quality
tibial nerve	UBERON:0001323	95.64	gold quality
right lung	UBERON:0002167	95.53	gold quality
right uterine tube	UBERON:0001302	95.28	gold quality
upper lobe of left lung	UBERON:0008952	95.27	gold quality
mucosa of stomach	UBERON:0001199	94.82	gold quality
adenohypophysis	UBERON:0002196	94.47	gold quality
right ovary	UBERON:0002118	94.34	gold quality
right adrenal gland	UBERON:0001233	94.33	gold quality
upper lobe of lung	UBERON:0008948	94.22	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.20	gold quality
right adrenal gland cortex	UBERON:0035827	94.14	gold quality
left lobe of thyroid gland	UBERON:0001120	94.04	gold quality
metanephros cortex	UBERON:0010533	93.90	gold quality
left adrenal gland cortex	UBERON:0035825	93.56	gold quality
left adrenal gland	UBERON:0001234	93.54	gold quality
right lobe of thyroid gland	UBERON:0001119	93.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.45	gold quality
thyroid gland	UBERON:0002046	93.19	gold quality
omental fat pad	UBERON:0010414	93.05	gold quality
peritoneum	UBERON:0002358	93.02	gold quality
sural nerve	UBERON:0015488	92.84	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.83	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	101.99
E-ANND-3	yes	9.35
E-GEOD-99795	no	671.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting IFI44, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-96-3P	97.47	68.03	839

Literature-anchored findings (GeneRIF, showing 8)

• Binds and depletes intracellular GTP, abolishing extracellular signal-regulated kinase (ERK) signaling and resulting finally in cell cycle arrest. (PMID:17784819)
• The restriction of Bunyamwera virus replication mediated by interferon is an accumulated effect of at least three interferon-stimulated genes viperin, MTAP44 and PKR. (PMID:22896602)
• IFI44 localizes to nuclei and suppresses HIV-1 LTR promoter. (PMID:25776761)
• The data indicate that binding of IFI44 to FKBP5 decreased the phosphorylation of IRF-3 and IkappaBalpha mediated by IKKepsilon and IKKbeta, respectively, providing a likely explanation for the function of IFI44 in negatively modulating IFN responses. (PMID:31455651)
• Interferon-Induced Protein 44 and Interferon-Induced Protein 44-Like Restrict Replication of Respiratory Syncytial Virus. (PMID:32611756)
• IFI44 is an immune evasion biomarker for SARS-CoV-2 and Staphylococcus aureus infection in patients with RA. (PMID:36189314)
• ACSL4 upregulates IFI44 and IFI44L expression and promotes the proliferation and invasiveness of head and neck squamous cell carcinoma cells. (PMID:38989827)
• Interferon-induced protein 44 (IFI44) and interferon regulatory factor 4 (IRF4) gene expression in rheumatoid arthritis. (PMID:39051937)

Cross-species orthologs

23 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-197g15.9	ENSDARG00000002293
danio_rerio	si:ch211-197g15.5	ENSDARG00000009673
danio_rerio		ENSDARG00000010729
danio_rerio	ifi44b	ENSDARG00000015678
danio_rerio	ifi44a1	ENSDARG00000029720
danio_rerio	ifi44e	ENSDARG00000056501
danio_rerio	ifi44c2	ENSDARG00000060322
danio_rerio	ifi44f4	ENSDARG00000071355
danio_rerio	ifi44f1	ENSDARG00000071361
danio_rerio	ifi44a3	ENSDARG00000075791
danio_rerio		ENSDARG00000089661
danio_rerio	ifi44a5	ENSDARG00000092361
		ENSDARG00000092634
danio_rerio	ifi44c1	ENSDARG00000092883
danio_rerio	ifi44a8	ENSDARG00000093857
danio_rerio	ifi44f5	ENSDARG00000094747
danio_rerio	ifi44f3	ENSDARG00000094984
danio_rerio	ifi44a7	ENSDARG00000095309
danio_rerio	ifi44a6	ENSDARG00000095673
danio_rerio		ENSDARG00000107486
		ENSDARG00000111120
mus_musculus	Ifi44	ENSMUSG00000028037
rattus_norvegicus	Ifi44	ENSRNOG00000022218

Paralogs (1): IFI44L (ENSG00000137959)

Protein

Protein identifiers

Interferon-induced protein 44 — Q8TCB0 (reviewed: Q8TCB0)

Alternative names: Microtubule-associated protein 44

All UniProt accessions (3): Q8TCB0, C9JUM8, H7C1F3

UniProt curated annotations — full annotation on UniProt →

Function. This protein aggregates to form microtubular structures.

Subcellular location. Cytoplasm.

Induction. By alpha and beta interferons, but not by gamma interferons.

Similarity. Belongs to the IFI44 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TCB0-1	1	yes
Q8TCB0-2	2

RefSeq proteins (1): NP_006408* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006571	TLDc_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF07534

UniProt features (7 total): splice variant 2, sequence conflict 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCB0-F1	87.46	0.54

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9909505	Modulation of host responses by IFN-stimulated genes

MSigDB gene sets: 364 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BECKER_TAMOXIFEN_RESISTANCE_UP, MODULE_45, MODULE_418, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, BROWNE_HCMV_INFECTION_16HR_UP, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN

GO Biological Process (5): immune response (GO:0006955), response to virus (GO:0009615), response to bacterium (GO:0009617), cellular response to virus (GO:0098586), response to other organism (GO:0051707)

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

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

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 other organism	2
cellular anatomical structure	2
immune system process	1
response to stimulus	1
response to virus	1
response to external biotic stimulus	1
biological process involved in interspecies interaction between organisms	1
binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1648 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFI44	IFIT3	O14879	914
IFI44	IFIT1	P09914	865
IFI44	MX1	P20591	849
IFI44	ISG15	P05161	829
IFI44	RSAD2	Q8WXG1	824
IFI44	IFI6	P09912	821
IFI44	OAS1	P00973	820
IFI44	IFIT2	P09913	818
IFI44	OASL	Q15646	778
IFI44	IRF7	Q92985	772
IFI44	IFI27	P40305	769
IFI44	EIF2AK2	P19525	760
IFI44	IFNB1	P01574	757
IFI44	IFITM3	Q01628	756
IFI44	IFIH1	Q9BYX4	751

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MAGEA11	IFI44	psi-mi:“MI:0915”(physical association)	0.560
IFNA21	IFIT3	psi-mi:“MI:0914”(association)	0.530
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
IFI44	MAGEA11	psi-mi:“MI:0915”(physical association)	0.000
IFI44	nrdF	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): IFI44 (Affinity Capture-MS), MAGEA11 (Two-hybrid), IFI44 (Proximity Label-MS), IFI44 (Affinity Capture-MS), IFI44 (Affinity Capture-MS), RALA (Cross-Linking-MS (XL-MS)), IFI44 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIF8, A0A2P1BRP3, A0A386CAB9, A0JN92, A1A4Y4, O14791, P27473, P59045, P86448, P86449, Q0GUM3, Q13075, Q3B7D9, Q3T9E4, Q3TL54, Q53G44, Q5NCI0, Q5RFJ8, Q60766, Q62293, Q66X01, Q66X03, Q66X05, Q66X22, Q6AYC2, Q6ZSC3, Q7Z745, Q84WJ0, Q86W28, Q8BV66, Q8BVM9, Q8C6J9, Q8CBA2, Q8CCN1, Q8TCB0, Q8TCY9, Q8TD90, Q90597, Q99388, Q99J64

Diamond homologs: P27473, Q53G44, Q8BV66, Q8TCB0, Q9BDB7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1634 predictions. Top by Δscore:

Variant	Effect	Δscore
1:78654280:G:GG	donor_gain	1.0000
1:78659310:A:AG	acceptor_gain	1.0000
1:78659311:G:GG	acceptor_gain	1.0000
1:78659480:GCTG:G	donor_gain	1.0000
1:78662797:G:GT	donor_gain	1.0000
1:78649902:ACAGG:A	donor_loss	0.9900
1:78649904:AGG:A	donor_loss	0.9900
1:78649906:G:GC	donor_loss	0.9900
1:78649907:T:G	donor_loss	0.9900
1:78650411:A:T	donor_gain	0.9900
1:78651125:G:GT	donor_gain	0.9900
1:78654278:GA:G	donor_gain	0.9900
1:78655360:A:AG	acceptor_gain	0.9900
1:78655361:G:GG	acceptor_gain	0.9900
1:78655361:GTATA:G	acceptor_gain	0.9900
1:78659311:GTT:G	acceptor_gain	0.9900
1:78659311:GTTT:G	acceptor_gain	0.9900
1:78659311:GTTTA:G	acceptor_gain	0.9900
1:78659467:G:GT	donor_gain	0.9900
1:78659484:G:GG	donor_gain	0.9900
1:78650406:G:GT	donor_gain	0.9800
1:78651150:G:GA	donor_gain	0.9800
1:78655361:GT:G	acceptor_gain	0.9800
1:78655464:G:T	donor_gain	0.9800
1:78659311:GT:G	acceptor_gain	0.9800
1:78659484:G:GA	donor_loss	0.9800
1:78659486:G:GC	donor_loss	0.9800
1:78659487:AGTCT:A	donor_loss	0.9800
1:78662703:GCTA:G	acceptor_gain	0.9800
1:78654661:G:GT	donor_gain	0.9700

AlphaMissense

2919 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:78650640:T:C	F149L	0.961
1:78650642:T:A	F149L	0.961
1:78650642:T:G	F149L	0.961
1:78655147:T:C	F210L	0.946
1:78655149:C:A	F210L	0.946
1:78655149:C:G	F210L	0.946
1:78655115:A:C	K199T	0.938
1:78655120:A:C	S201R	0.937
1:78655122:C:A	S201R	0.937
1:78655122:C:G	S201R	0.937
1:78655115:A:T	K199M	0.925
1:78655123:T:C	F202L	0.917
1:78655125:T:A	F202L	0.917
1:78655125:T:G	F202L	0.917
1:78655116:G:C	K199N	0.916
1:78655116:G:T	K199N	0.916
1:78655489:G:T	G273V	0.914
1:78650433:T:C	F80L	0.910
1:78650435:T:A	F80L	0.910
1:78650435:T:G	F80L	0.910
1:78662731:T:C	F381L	0.909
1:78662733:T:A	F381L	0.909
1:78662733:T:G	F381L	0.909
1:78650641:T:C	F149S	0.907
1:78650347:T:C	L51P	0.905
1:78659389:T:G	C306W	0.905
1:78655410:T:C	F247L	0.895
1:78655412:T:A	F247L	0.895
1:78655412:T:G	F247L	0.895
1:78662848:T:C	F420L	0.894

dbSNP variants (sampled 300 via entrez): RS1000022351 (1:78664213 T>C), RS1000143527 (1:78648649 C>G,T), RS1000184362 (1:78658254 T>G), RS1000378209 (1:78651825 T>C), RS1000436283 (1:78661611 A>G), RS1000505940 (1:78654903 A>C), RS1000660827 (1:78658063 A>G), RS1000750362 (1:78653469 T>G), RS1000862270 (1:78652061 C>A,T), RS1000919479 (1:78659918 A>T), RS1000976384 (1:78648114 G>A), RS1001084609 (1:78649207 T>G), RS1001261042 (1:78656554 C>A,T), RS1001345315 (1:78647837 T>G), RS1001463717 (1:78650883 C>T)

Disease associations

OMIM: gene MIM:610468 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001877_50	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	1.000000e-06
GCST005212_14	Asthma	5.000000e-06
GCST006284_18	Plasma proprotein convertase subtilisin/kexin type 9 levels in stable coronary artery disease	6.000000e-07
GCST009391_191	Metabolite levels	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006899	PCSK9 protein measurement
EFO:0010482	gamma-aminoisobutyric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance, affects expression, affects cotreatment	7
(+)-JQ1 compound	decreases expression	3
Air Pollutants	decreases expression, increases abundance	3
Plant Extracts	affects expression, affects reaction, affects cotreatment, increases expression	3
Silicon Dioxide	increases expression	3
Tretinoin	decreases expression, increases expression	3
Cyclosporine	increases expression, affects expression, decreases expression	3
Acetaminophen	decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Lipopolysaccharides	affects expression, increases expression, affects reaction, affects response to substance	2
Nickel	increases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
TL8-506	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	increases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
chloroquine diphosphate	decreases expression	1
nickel sulfate	increases expression	1
hydroquinone	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	decreases expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1FR	Abcam A-549 IFI44 KO 1	Cancer cell line	Male
CVCL_B2NA	Abcam A-549 IFI44 KO 2	Cancer cell line	Male
CVCL_E1ZR	HAP1 IFI44 (-) 2	Cancer cell line	Male
CVCL_XP71	HAP1 IFI44 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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