AIF1L

Summary

AIF1L (allograft inflammatory factor 1 like, HGNC:28904) is a protein-coding gene on chromosome 9q34.12-q34.13, encoding Allograft inflammatory factor 1-like (Q9BQI0). Actin-binding protein that promotes actin bundling.

Enables actin filament binding activity. Predicted to be involved in actin filament bundle assembly and ruffle assembly. Located in actin filament and focal adhesion. Biomarker of breast cancer.

Source: NCBI Gene 83543 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_031426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28904
Approved symbol	AIF1L
Name	allograft inflammatory factor 1 like
Location	9q34.12-q34.13
Locus type	gene with protein product
Status	Approved
Aliases	IBA2, FLJ12783
Ensembl gene	ENSG00000126878
Ensembl biotype	protein_coding
OMIM	621223
Entrez	83543

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000247291, ENST00000372297, ENST00000372298, ENST00000372300, ENST00000372301, ENST00000372302, ENST00000372309, ENST00000372314, ENST00000472942, ENST00000478257, ENST00000896316

RefSeq mRNA: 3 — MANE Select: NM_031426 NM_001185095, NM_001185096, NM_031426

CCDS: CCDS55348, CCDS55349, CCDS6939

Canonical transcript exons

ENST00000247291 — 6 exons

Exon	Start	End
ENSE00003460375	131111597	131111663
ENSE00003477407	131114577	131114618
ENSE00003591318	131117756	131117918
ENSE00003616673	131096802	131096863
ENSE00003842312	131096531	131096660
ENSE00003846601	131120235	131123144

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.3013 / max 828.4339, expressed in 1056 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99051	38.9767	1040
99050	1.9754	714
99058	0.1094	23
99061	0.0943	35
99057	0.0693	19
99054	0.0307	11
99056	0.0222	10
99055	0.0129	6
99053	0.0057	3
99052	0.0045	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	99.74	gold quality
kidney epithelium	UBERON:0004819	99.63	gold quality
metanephros cortex	UBERON:0010533	99.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.01	gold quality
inferior vagus X ganglion	UBERON:0005363	98.99	gold quality
adult mammalian kidney	UBERON:0000082	98.91	gold quality
spinal cord	UBERON:0002240	98.89	gold quality
spleen	UBERON:0002106	98.25	gold quality
lower esophagus mucosa	UBERON:0035834	98.13	gold quality
medial globus pallidus	UBERON:0002477	98.12	gold quality
ventral tegmental area	UBERON:0002691	97.90	gold quality
medulla oblongata	UBERON:0001896	97.86	gold quality
globus pallidus	UBERON:0001875	97.79	gold quality
ventricular zone	UBERON:0003053	97.76	gold quality
midbrain	UBERON:0001891	97.62	gold quality
substantia nigra	UBERON:0002038	97.60	gold quality
kidney	UBERON:0002113	97.47	gold quality
dorsal root ganglion	UBERON:0000044	97.41	gold quality
trigeminal ganglion	UBERON:0001675	97.27	gold quality
superior vestibular nucleus	UBERON:0007227	97.24	gold quality
putamen	UBERON:0001874	97.19	gold quality
amygdala	UBERON:0001876	97.18	gold quality
endothelial cell	CL:0000115	96.78	gold quality
subthalamic nucleus	UBERON:0001906	96.46	gold quality
esophagus squamous epithelium	UBERON:0006920	95.96	gold quality
corpus callosum	UBERON:0002336	95.91	gold quality
pons	UBERON:0000988	95.87	gold quality
thyroid gland	UBERON:0002046	95.82	gold quality
hypothalamus	UBERON:0001898	95.78	gold quality
right lobe of thyroid gland	UBERON:0001119	95.67	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	83.91
E-HCAD-10	yes	40.22
E-MTAB-6678	yes	16.67
E-GEOD-93593	yes	16.23
E-MTAB-10137	yes	4.68
E-CURD-11	no	40.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

137 targeting AIF1L, 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-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1273H-5P	99.77	66.32	2471

Literature-anchored findings (GeneRIF, showing 3)

• Structure of human Iba2 and its homodimerization properties, F-actin cross-linking activity, cellular localization and recruitment upon bacterial invasion in comparison with Iba1. (PMID:18699778)
• We did not find the AIF1L-ETV6 and ABL1-AIF1L fusions in other ETV6-ABL1-positive ALL. Nevertheless, functional studies would be needed to establish the biological role of AIF1L-ETV6 and ABL1-AIF1L and to determine whether they contribute to leukemogenesis and/or to the final leukemia phenotype. (PMID:29726059)
• these findings indicate an involvement of AIF1L in the stabilization of podocyte morphology by titrating actomyosin contractility and membrane dynamics. (PMID:30001384)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	aif1l	ENSDARG00000009336
mus_musculus	Aif1l	ENSMUSG00000001864
rattus_norvegicus	Aif1l	ENSRNOG00000009951

Paralogs (1): AIF1 (ENSG00000204472)

Protein

Protein identifiers

Allograft inflammatory factor 1-like — Q9BQI0 (reviewed: Q9BQI0)

Alternative names: Ionized calcium-binding adapter molecule 2

All UniProt accessions (5): Q9BQI0, A6PVM9, H7C605, Q5JUP1, Q5JUP3

UniProt curated annotations — full annotation on UniProt →

Function. Actin-binding protein that promotes actin bundling. May neither bind calcium nor depend on calcium for function.

Subunit / interactions. Homodimer (Potential). Monomer.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Ruffle membrane.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BQI0-1	1	yes
Q9BQI0-2	2
Q9BQI0-3	3
Q9BQI0-4	4

RefSeq proteins (3): NP_001172024, NP_001172025, NP_113614* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR042433	AIF1/AIF1L	Family
IPR049025	AIF-1_EF_pair	Domain

Pfam: PF21008

UniProt features (27 total): helix 7, splice variant 4, binding site 4, modified residue 3, strand 3, domain 2, initiator methionine 1, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2JJZ	X-RAY DIFFRACTION	2.15
2VTG	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQI0-F1	84.82	0.60

Functional residue map

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

Ligand- & substrate-binding residues (4): 60; 62; 64; 66

Post-translational modifications (3): 2, 134, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 158 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, AP4_Q6, GOCC_RUFFLE, CAGCTG_AP4_Q5, GTGCCTT_MIR506, MARTINEZ_RB1_TARGETS_UP, GOBP_ACTIN_FILAMENT_ORGANIZATION, HNF4_DR1_Q3, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, TGANTCA_AP1_C, GATA1_04, GOMF_ACTIN_BINDING, LEF1_Q6, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (2): actin filament bundle assembly (GO:0051017), ruffle assembly (GO:0097178)

GO Molecular Function (5): calcium ion binding (GO:0005509), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (10): focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), ruffle membrane (GO:0032587), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), actin filament (GO:0005884), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular component assembly	1
actin filament bundle organization	1
ruffle organization	1
plasma membrane bounded cell projection assembly	1
metal ion binding	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
binding	1
cation binding	1
cell-substrate junction	1
cytoskeleton	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
extracellular vesicle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1966 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AIF1L	CPVL	Q9H3G5	460
AIF1L	DPPA4	Q7L190	389
AIF1L	HABP4	Q5JVS0	388
AIF1L	NAA11	Q9BSU3	343
AIF1L	FDXACB1	Q9BRP7	336
AIF1L	SLAMF8	Q9P0V8	327
AIF1L	WDR38	Q5JTN6	317
AIF1L	PDE6G	P18545	314
AIF1L	ARHGEF18	Q6ZSZ5	311
AIF1L	A0A087WZG4	A0A087WZG4	309
AIF1L	G3V325	G3V325	295
AIF1L	LY86	O95711	283
AIF1L	TBCB	Q99426	279
AIF1L	ASB2	Q96Q27	276
AIF1L	PPP3R1	P06705	272

IntAct

19 interactions, top by confidence:

A	B	Type	Score
PROM1	AIF1L	psi-mi:“MI:0915”(physical association)	0.370
SPHK1	TAF4	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
FGFR2	LANCL1	psi-mi:“MI:0914”(association)	0.350
rep	LAD1	psi-mi:“MI:0914”(association)	0.350
	PDLIM1	psi-mi:“MI:0914”(association)	0.350
TMIGD1	LAD1	psi-mi:“MI:0914”(association)	0.350
ACTN4		psi-mi:“MI:0914”(association)	0.350
CALD1		psi-mi:“MI:0914”(association)	0.350
CALM3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
CTTN		psi-mi:“MI:0914”(association)	0.350
EEA1	PARP1	psi-mi:“MI:0914”(association)	0.350
RIPK3	AIF1L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (86): AIF1L (Affinity Capture-MS), AIF1L (Affinity Capture-MS), AIF1L (Affinity Capture-MS), AIF1L (Affinity Capture-MS), AIF1L (Affinity Capture-MS), AIF1L (Two-hybrid), TSEN15 (Two-hybrid), AIF1L (Affinity Capture-MS), AIF1L (Affinity Capture-MS), AIF1L (Proximity Label-MS), AIF1L (Affinity Capture-MS), AIF1L (Affinity Capture-MS), AIF1L (Affinity Capture-MS), AIF1L (Affinity Capture-MS), AIF1L (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6A2H6, A2VEI2, A4IG32, A4IHK8, A5D7A0, D2HZB0, D4A1F2, E9Q4Z2, F1MF74, O00763, O08874, O14795, O94851, P23092, Q05AA6, Q08BI9, Q13474, Q17QM6, Q3TWN3, Q4FZY0, Q4KUS2, Q4V8B2, Q5E9V1, Q5R9G1, Q5RDI4, Q5U2P1, Q5ZJT0, Q62768, Q62769, Q69ZT9, Q6DFA1, Q86XE3, Q8BHD4, Q8BML1, Q8IWE4, Q8K0V2, Q8WN03, Q96C19, Q9BQI0, Q9BUP0

Diamond homologs: A5D7A0, O70200, O81092, P04112, P04113, P05944, P29289, P54680, P55008, P55009, P81076, Q09011, Q11083, Q17QM6, Q32LE3, Q4FZY0, Q54QX0, Q5RDI4, Q5TM25, Q8VWY7, Q96C19, Q9AWK2, Q9BDK2, Q9BQI0, Q9BUP0, Q9D4J1, Q9D8Y0, Q9EQX4, Q9SRP7, Q9VJ26, O60041, O96102, P06787, P14533, P25071, P80322, Q09665, Q12798, Q9XZP2, A3E3H0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

986 predictions. Top by Δscore:

Variant	Effect	Δscore
9:131096658:AAG:A	donor_loss	1.0000
9:131096659:AGG:A	donor_loss	1.0000
9:131096661:G:GA	donor_loss	1.0000
9:131096662:T:A	donor_loss	1.0000
9:131111595:A:AG	acceptor_gain	1.0000
9:131111595:A:AT	acceptor_loss	1.0000
9:131111595:AG:A	acceptor_gain	1.0000
9:131111596:G:GG	acceptor_gain	1.0000
9:131111596:GG:G	acceptor_gain	1.0000
9:131111596:GGA:G	acceptor_gain	1.0000
9:131111596:GGAGT:G	acceptor_gain	1.0000
9:131111661:AAG:A	donor_gain	1.0000
9:131111661:AAGG:A	donor_loss	1.0000
9:131111662:AG:A	donor_gain	1.0000
9:131111662:AGGTA:A	donor_loss	1.0000
9:131111663:GG:G	donor_gain	1.0000
9:131111664:G:GA	donor_loss	1.0000
9:131111664:G:GG	donor_gain	1.0000
9:131114567:T:TA	acceptor_gain	1.0000
9:131114571:TTCCA:T	acceptor_loss	1.0000
9:131114572:TCCA:T	acceptor_loss	1.0000
9:131114574:CA:C	acceptor_loss	1.0000
9:131114575:A:AG	acceptor_gain	1.0000
9:131114575:AGAGA:A	acceptor_loss	1.0000
9:131114576:G:GA	acceptor_gain	1.0000
9:131114576:G:GC	acceptor_loss	1.0000
9:131114576:GA:G	acceptor_gain	1.0000
9:131114576:GAGAA:G	acceptor_gain	1.0000
9:131114614:GATTG:G	donor_gain	1.0000
9:131114619:G:GC	donor_loss	1.0000

AlphaMissense

1004 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:131117861:T:A	I103K	0.999
9:131117875:T:C	F108L	0.999
9:131117877:T:A	F108L	0.999
9:131117877:T:G	F108L	0.999
9:131111649:T:A	L49H	0.998
9:131111649:T:C	L49P	0.998
9:131114582:T:G	Y56D	0.998
9:131114591:T:C	F59L	0.998
9:131114593:T:A	F59L	0.998
9:131114593:T:G	F59L	0.998
9:131117866:T:G	Y105D	0.998
9:131117876:T:C	F108S	0.998
9:131120245:T:C	F126L	0.998
9:131120247:T:A	F126L	0.998
9:131120247:T:G	F126L	0.998
9:131117772:G:C	K73N	0.997
9:131117772:G:T	K73N	0.997
9:131117804:C:T	T84I	0.997
9:131117861:T:G	I103R	0.997
9:131114583:A:C	Y56S	0.996
9:131117802:G:C	K83N	0.996
9:131117802:G:T	K83N	0.996
9:131117806:C:G	H85D	0.996
9:131117808:C:A	H85Q	0.996
9:131117808:C:G	H85Q	0.996
9:131117861:T:C	I103T	0.996
9:131117866:T:C	Y105H	0.996
9:131117879:T:A	V109E	0.996
9:131117768:T:C	L72S	0.995
9:131117810:T:C	L86P	0.995

dbSNP variants (sampled 300 via entrez): RS1000017386 (9:131111933 G>A,C), RS1000039366 (9:131108372 G>C), RS1000050163 (9:131111663 G>A,T), RS1000126309 (9:131103131 G>A), RS1000228085 (9:131100706 C>T), RS1000257510 (9:131100511 C>G), RS1000292726 (9:131117177 C>T), RS1000411962 (9:131108715 G>A,C), RS1000491785 (9:131096461 A>C,G,T), RS1000578322 (9:131123638 G>C), RS1000582158 (9:131106386 G>A), RS1000757355 (9:131118282 G>A), RS1000773428 (9:131096705 G>A,C), RS1000976970 (9:131112716 A>C), RS1001017455 (9:131107300 G>C)

Disease associations

OMIM: gene MIM:621223 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression, decreases expression	6
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
bisphenol A	decreases methylation, decreases expression, affects cotreatment	2
sodium arsenite	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
FR900359	increases phosphorylation	1
propionaldehyde	increases expression	1
lead acetate	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
tobacco tar	decreases expression	1
coumarin	decreases phosphorylation	1
pentanal	increases expression	1
avobenzone	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Aldehydes	increases expression	1
Aspirin	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Cocaine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_X907	TK-6 [Human leukemia]	Cancer cell line	Male

Clinical trials (associated diseases)

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