AIF1

Summary

AIF1 (allograft inflammatory factor 1, HGNC:352) is a protein-coding gene on chromosome 6p21.33, encoding Allograft inflammatory factor 1 (P55008). Actin-binding protein that enhances membrane ruffling and RAC activation.

This gene encodes a protein that binds actin and calcium. This gene is induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes. Polymorphisms in this gene may be associated with systemic sclerosis. Alternative splicing results in multiple transcript variants, but the full-length and coding nature of some of these variants is not certain.

Source: NCBI Gene 199 — RefSeq curated summary.

At a glance

• GWAS associations: 41
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_001623

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:352
Approved symbol	AIF1
Name	allograft inflammatory factor 1
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	IRT-1, AIF-1, Em:AF129756.17, IBA1
Ensembl gene	ENSG00000204472
Ensembl biotype	protein_coding
OMIM	601833
Entrez	199

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 retained_intron

ENST00000337917, ENST00000376049, ENST00000376059, ENST00000466820, ENST00000497362, ENST00000889060

RefSeq mRNA: 3 — MANE Select: NM_001623 NM_001318970, NM_001623, NM_032955

CCDS: CCDS34398, CCDS4706

Canonical transcript exons

ENST00000376059 — 6 exons

Exon	Start	End
ENSE00001666380	31615670	31615736
ENSE00001696262	31616104	31616145
ENSE00001882020	31615234	31615354
ENSE00003299262	31616344	31616506
ENSE00003581585	31615521	31615582
ENSE00003843233	31616816	31617015

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 99.80.

FANTOM5 (CAGE): breadth broad, TPM avg 87.6264 / max 5534.2276, expressed in 704 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66969	62.5854	513
66975	10.9164	421
66974	8.8060	489
66971	2.8744	369
66973	0.8937	237
66977	0.6338	193
66976	0.4996	88
66972	0.2554	114
66970	0.1618	85

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.80	gold quality
leukocyte	CL:0000738	99.78	gold quality
granulocyte	CL:0000094	99.61	gold quality
bone marrow cell	CL:0002092	98.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.47	gold quality
right lung	UBERON:0002167	97.40	gold quality
gall bladder	UBERON:0002110	97.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.31	gold quality
rectum	UBERON:0001052	96.04	gold quality
spleen	UBERON:0002106	96.01	gold quality
right coronary artery	UBERON:0001625	95.89	gold quality
smooth muscle tissue	UBERON:0001135	95.55	gold quality
upper lobe of left lung	UBERON:0008952	95.54	gold quality
calcaneal tendon	UBERON:0003701	94.39	gold quality
colonic epithelium	UBERON:0000397	93.94	gold quality
omental fat pad	UBERON:0010414	93.74	gold quality
descending thoracic aorta	UBERON:0002345	93.64	gold quality
peritoneum	UBERON:0002358	93.60	gold quality
right adrenal gland cortex	UBERON:0035827	92.66	gold quality
left coronary artery	UBERON:0001626	92.52	gold quality
right adrenal gland	UBERON:0001233	92.27	gold quality
mucosa of transverse colon	UBERON:0004991	91.92	gold quality
upper lobe of lung	UBERON:0008948	91.82	gold quality
left adrenal gland	UBERON:0001234	91.65	gold quality
thoracic aorta	UBERON:0001515	91.58	gold quality
left adrenal gland cortex	UBERON:0035825	91.46	gold quality
ascending aorta	UBERON:0001496	91.29	gold quality
spinal cord	UBERON:0002240	90.91	gold quality
lymph node	UBERON:0000029	90.90	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.85	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 30.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	3360.46
E-MTAB-7407	yes	1549.94
E-MTAB-10287	yes	1462.91
E-MTAB-10662	yes	1262.51
E-MTAB-9388	yes	1184.59
E-MTAB-9221	yes	1001.55
E-MTAB-6701	yes	917.52
E-GEOD-84465	yes	890.07
E-CURD-98	yes	761.53
E-HCAD-10	yes	755.73
E-GEOD-149689	yes	714.96
E-MTAB-6075	yes	582.53
E-HCAD-56	yes	437.50
E-HCAD-4	yes	295.19
E-GEOD-130473	yes	285.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SPI1

miRNA regulators (miRDB)

8 targeting AIF1, 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-587	99.64	70.86	2611
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-6861-5P	96.23	67.19	800
HSA-MIR-6835-5P	95.81	64.27	500
HSA-MIR-4522	95.76	66.23	742
HSA-MIR-1298-3P	94.05	64.84	620

Literature-anchored findings (GeneRIF, showing 40)

• AIF-1 binds and polymerizes F actin and also regulates Rac1 activity and vascular smooth muscle migration (PMID:12714565)
• more AIF-1 immunoreactive macrophages/microglial cells and, interestingly, neurones were observed in Creutzfeldt-Jakob disease patients (PMID:12887599)
• AIF-1 enhances VSMC growth by autocrine production of G-CSF, and AIF-1 expression may influence VSMC-inflammatory cell communication. (PMID:15117732)
• Genomic rearrangement of AIF1 in arteriosclerosis was studied. (PMID:15784173)
• The ability of AIF-1 to activate vascular smooth muscle is lost by mutation in the EF-hand calcium-binding region. (PMID:15922740)
• Overexpression of allograft inflammatory factor-1 is associated with development of coronary artery vasculopathy (PMID:16049345)
• These data indicate that AIF-1 mediates atherogenesis-initiated signaling and activation of macrophages. (PMID:16291819)
• The subtle regulation of allograft inflammatory factor-1 in the involution of hemangiomas will help design a new anti-angiogenic therapy for some tumors. [REVIEW] (PMID:17010532)
• The molecular conformational change induced by Ca(2+)-binding of Iba1 is different from that found in the classical EF-hand proteins, which demonstrates that Iba1 has an unique molecular switching mechanism dependent on Ca(2+)-binding. (PMID:17011575)
• AIF-1 is a novel molecular component of podocytes and the upregulation of AIF-1 in an anti-GBM nephritis model may mainly be a consequence of its expression in infiltrating cells. (PMID:17035944)
• Crystals of AIF-1 were grown at 291 K using PEG-8000 as precipitant, and diffraction extends to 3.3 A resolution. (PMID:17073733)
• association of a nonsynonymous change within the AIF-1 gene with systemic sclerosis, and linkage with TNFA alleles within 50 kb of this gene (PMID:17498268)
• a genetic association between AIF1 and the anti-centromere antibodies-positive subset of systemic sclerosis. (PMID:17522098)
• Using immunohistochemistry, we found that AIF-1 is expressed at low levels in normal skin, but is highly upregulated in various inflammatory skin disorders (PMID:17533487)
• These results suggest that AIF-1 may participate in the early pathogenesis of systemic sclerosis by promoting tissue T cell infiltration and production of cytokines capable of inducing the expression of a fibrotic phenotype in normal fibroblasts. (PMID:17907195)
• daintain/AIF-1 can promote the growth of breast tumors via activating NF-kappaB signaling, which consequently up-regulates the expression of cyclin D1. (PMID:18341653)
• The AIF1 rs2269475 T allele is associated with increased risk of rheumatoid arthritis development. (PMID:18721278)
• AIF-1 expression regulates endothelial cell activation, signal transduction, and vasculogenesis. (PMID:18787073)
• AIF-1 plays a role in inflammatory nerve disease and vascular smooth muscle cell proliferation and may be a new molecular target for treatment. (PMID:18816612)
• Genetic variants of the HLA-A, HLA-B and AIF1 loci show independent associations with type 1 diabetes in Norwegian families (PMID:18987644)
• findings suggest that the impact of AIF-1 on endothelial cells would stimulate angiogenesis and consequently affect the progression of infantile hemangiomas (PMID:19745784)
• AIF-1 shows promise that it can be a potential biomarker for cardiac allograft rejection. (PMID:20850992)
• AIF-1 can induce IL-6 secretion on mononuclear cells and fibroblast chemotaxis. AIF-1 may accordingly provide an attractive new target for antifibrotic therapy in SSc as well as Scl GVHD. (PMID:21040744)
• data demonstrated that expression profiles of AIF-1 and TLR-2 correlated with biopsy-proven allograft rejection in both peripheral blood and local tissue, suggesting their potential as diagnostic biomarkers for early detection of allograft rejection (PMID:21168672)
• daintain/AIF-1 activates p38 MAPK signaling pathway contributing to up-regulation of TNF-alpha in MDA-MB-231 and MCF-7 cells. (PMID:21509525)
• Our data suggest that SNPs in or near the AIF1 locus contribute to obesity risk in the Greek population. (PMID:21720444)
• Our results suggest that the AIF1 rs2259571 CC genotype is associated with the active form of RA. (PMID:22106834)
• Overexpression of AIF-1 stimulates migration and proliferation of human vascular smooth muscle cells, whereas IRT-1 exerts opposite effects. (PMID:22116621)
• The serum AIF-1 concentrations were positively correlated with levels of fasting plasma glucose, hemoglobin A1c, triglycerides, and uric acid, and with waist circumference and BMI, and were inversely correlated with HDL cholesterol levels. (PMID:22225958)
• Serum AIF-1 concentration correlated with albuminuria and eGFR in patients with type 2 diabetes and it could be a marker of diabetic nephropathy as well as activated macrophages. (PMID:22560794)
• daintain/AIF-1 reinforced the resistance of breast cancer cells to cisplatin by inhibition of cell apoptosis and reduction of intracellular cisplatin accumulation (PMID:23221708)
• AIF-1 can protect rheumatoid arthritis fibroblast-like synoviocytes from apoptosis induced by NO by upregulating the expression of p-Akt and p-BAD. (PMID:23547889)
• We are unable to find statistically significant association between COX-2 and AIF-1 gene polymorphisms and allograft survival. (PMID:23777936)
• The overexpressed AIF-1, the novel inflammatory polypeptide derived from macrophage lineages, is closely associated with atherogenesis via affecting the blood composition and promoting macrophage uptake and foam cell formation. (PMID:23867161)
• The results of this study suggest that the patients with the rs2259571 CC AIF1 genotype have a poorer response to therapy with Methotrexate. (PMID:24018427)
• AIF-1 functions as a tumor suppressor possibly by regulating beta-catenin in gastric cancer. the level of AIF-1 expression may serve as a protective prognostic indicator for gastric cancer. (PMID:24337893)
• AIF-1, which induced chemokines and enhanced chemotaxis of monocytes, may represent a molecular target for the therapy of immune-inflammatory disorders (PMID:24796669)
• The results of this study suggest a lack of association between AIF-1 gene polymorphisms and response to sulphasalazine treatment in rheumatoid arthritis. (PMID:25026748)
• Data showed that AIF-1 promoted the proliferation of HepG2 cells by accelerating the activation of IGF-1R and its downstream signaling pathway, which confirms that AIF-1 plays a crucial role in the development of hepatocellular carcinoma cells. (PMID:25998745)
• The results of our study suggest that the AIF1 gene polymorphisms have no influence on long-term kidney allograft function. (PMID:26324213)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Aif1	ENSMUSG00000024397
rattus_norvegicus	Aif1	ENSRNOG00000000853

Paralogs (1): AIF1L (ENSG00000126878)

Protein

Protein identifiers

Allograft inflammatory factor 1 — P55008 (reviewed: P55008)

Alternative names: Ionized calcium-binding adapter molecule 1, Protein G1

All UniProt accessions (4): P55008, I3WTX1, Q4V347, Q5STX8

UniProt curated annotations — full annotation on UniProt →

Function. Actin-binding protein that enhances membrane ruffling and RAC activation. Enhances the actin-bundling activity of LCP1. Binds calcium. Plays a role in RAC signaling and in phagocytosis. May play a role in macrophage activation and function. Promotes the proliferation of vascular smooth muscle cells and of T-lymphocytes. Enhances lymphocyte migration. Plays a role in vascular inflammation.

Subunit / interactions. Homodimer (Potential). Monomer. Interacts with LCP1.

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

Tissue specificity. Detected in T-lymphocytes and peripheral blood mononuclear cells.

Post-translational modifications. Phosphorylated on serine residues.

Isoforms (3)

UniProt ID	Names	Canonical?
P55008-1	1	yes
P55008-2	2, G1
P55008-3	3

RefSeq proteins (3): NP_001305899, NP_001614, NP_116573 (=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 (30 total): helix 7, binding site 6, modified residue 3, splice variant 3, strand 3, sequence conflict 2, domain 2, initiator methionine 1, chain 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2D58	X-RAY DIFFRACTION	1.9
2G2B	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55008-F1	87.07	0.64

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 (6): 105; 58; 60; 62; 64; 100

Post-translational modifications (3): 2, 11, 39

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 415 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, MODULE_151, MODULE_45, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_MIGRATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, MODULE_128, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION

GO Biological Process (27): microglial cell activation (GO:0001774), phagocytosis, engulfment (GO:0006911), inflammatory response (GO:0006954), positive regulation of cell population proliferation (GO:0008284), regulation of gene expression (GO:0010468), Rac protein signal transduction (GO:0016601), actin filament polymerization (GO:0030041), parallel actin filament bundle assembly (GO:0030046), positive regulation of cell migration (GO:0030335), positive regulation of chemokine production (GO:0032722), positive regulation of interleukin-6 production (GO:0032755), cellular response to oxidative stress (GO:0034599), positive regulation of T cell proliferation (GO:0042102), positive regulation of smooth muscle cell proliferation (GO:0048661), negative regulation of smooth muscle cell proliferation (GO:0048662), positive regulation of chemotaxis (GO:0050921), actin filament bundle assembly (GO:0051017), actin crosslink formation (GO:0051764), cellular response to type II interferon (GO:0071346), negative regulation of smooth muscle cell chemotaxis (GO:0071672), positive regulation of smooth muscle cell chemotaxis (GO:0071673), positive regulation of mononuclear cell migration (GO:0071677), positive regulation of monocyte chemotaxis (GO:0090026), positive regulation of fibroblast growth factor production (GO:0090271), ruffle assembly (GO:0097178), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), positive regulation of T cell migration (GO:2000406)

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 (14): ruffle (GO:0001726), phagocytic cup (GO:0001891), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), actin filament (GO:0005884), lamellipodium (GO:0030027), ruffle membrane (GO:0032587), perinuclear region of cytoplasm (GO:0048471), glial cell projection (GO:0097386), cytoskeleton (GO:0005856), 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	6
plasma membrane bounded cell projection	3
positive regulation of cytokine production	2
smooth muscle cell proliferation	2
regulation of smooth muscle cell proliferation	2
cell leading edge	2
cytoplasm	2
leukocyte activation involved in inflammatory response	1
macrophage activation	1
glial cell activation	1
phagocytosis	1
plasma membrane invagination	1
defense response	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
small GTPase-mediated signal transduction	1
actin polymerization or depolymerization	1
protein polymerization	1
actin filament bundle assembly	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
chemokine production	1
regulation of chemokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
response to oxidative stress	1
cellular response to chemical stress	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
positive regulation of cell population proliferation	1
negative regulation of cell population proliferation	1
chemotaxis	1
positive regulation of response to external stimulus	1
positive regulation of locomotion	1

Protein interactions and networks

STRING

4416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AIF1	GFAP	P14136	914
AIF1	RBFOX3	A6NFN3	905
AIF1	CD68	P34810	852
AIF1	IL1B	P01584	828
AIF1	TNF	P01375	826
AIF1	ITGAM	P11215	799
AIF1	NFKB1	P19838	791
AIF1	TMEM119	Q4V9L6	787
AIF1	DLG4	P78352	782
AIF1	CSF1R	P07333	779
AIF1	IL6	P05231	778
AIF1	CX3CR1	P49238	772
AIF1	OLIG2	Q13516	771
AIF1	MBP	P02686	769
AIF1	APP	P05067	765

IntAct

12 interactions, top by confidence:

A	B	Type	Score
AIF1	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
AIF1	GSN	psi-mi:“MI:0915”(physical association)	0.560
HSFY1	NDUFS1	psi-mi:“MI:0914”(association)	0.530
CHCHD4	HAX1	psi-mi:“MI:0914”(association)	0.350
KRT27	CCDC88B	psi-mi:“MI:0914”(association)	0.350
AIF1	YLPM1	psi-mi:“MI:0914”(association)	0.350
AIF1	PHB1	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (12): AIF1 (Proximity Label-MS), SNIP1 (Affinity Capture-MS), WDR33 (Affinity Capture-MS), RRP36 (Affinity Capture-MS), AIF1 (Affinity Capture-MS), YLPM1 (Affinity Capture-MS), ZC3H4 (Affinity Capture-MS), USP36 (Affinity Capture-MS), AIF1 (Affinity Capture-MS), AIF1 (Proximity Label-MS), AIF1 (Affinity Capture-Luminescence), AIF1 (Affinity Capture-MS)

ESM2 similar proteins: A0AVX7, A2VEI2, F4J0W4, O43745, O70200, O73761, O73762, P04354, P04467, P05937, P07171, P12658, P22728, P41044, P43080, P43081, P46065, P51177, P55008, P61022, P61023, P79880, P81076, Q0V9B1, Q1LWZ0, Q298L5, Q3KQ77, Q3SYS6, Q3T024, Q4R760, Q4V7T8, Q5R4V1, Q5R7F0, Q5TM25, Q5U554, Q5ZM44, Q6P8Y1, Q810D1, Q8IMX7, Q8R426

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

580 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31615516:CACA:C	acceptor_loss	1.0000
6:31615519:A:AG	acceptor_gain	1.0000
6:31615520:G:GG	acceptor_gain	1.0000
6:31615556:G:GT	donor_gain	1.0000
6:31615579:CAAGG:C	donor_loss	1.0000
6:31615580:AAGGT:A	donor_loss	1.0000
6:31615581:AGGT:A	donor_loss	1.0000
6:31615583:G:C	donor_loss	1.0000
6:31615584:T:A	donor_loss	1.0000
6:31615590:G:GT	donor_gain	1.0000
6:31616335:T:A	acceptor_gain	1.0000
6:31616340:CCAG:C	acceptor_loss	1.0000
6:31616342:A:AG	acceptor_gain	1.0000
6:31616342:AGAT:A	acceptor_loss	1.0000
6:31616343:G:GA	acceptor_gain	1.0000
6:31616343:GA:G	acceptor_gain	1.0000
6:31616343:GAT:G	acceptor_gain	1.0000
6:31616343:GATA:G	acceptor_gain	1.0000
6:31616343:GATAT:G	acceptor_gain	1.0000
6:31616471:G:GT	donor_gain	1.0000
6:31616502:AAAAT:A	donor_gain	1.0000
6:31616503:AAAT:A	donor_gain	1.0000
6:31616504:AAT:A	donor_gain	1.0000
6:31616504:AATGT:A	donor_loss	1.0000
6:31616505:AT:A	donor_gain	1.0000
6:31616505:ATGTG:A	donor_loss	1.0000
6:31616506:TG:T	donor_loss	1.0000
6:31616507:G:GG	donor_gain	1.0000
6:31616507:GTGA:G	donor_loss	1.0000
6:31615328:C:G	donor_gain	0.9900

AlphaMissense

974 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31616404:T:C	L86P	0.994
6:31616356:T:C	L70P	0.992
6:31616360:A:C	K71N	0.989
6:31616360:A:T	K71N	0.989
6:31616463:T:C	F106L	0.989
6:31616465:T:A	F106L	0.989
6:31616465:T:G	F106L	0.989
6:31615735:A:C	K51N	0.988
6:31615735:A:T	K51N	0.988
6:31616359:A:T	K71I	0.987
6:31616109:T:G	Y54D	0.986
6:31616454:T:G	Y103D	0.986
6:31616118:T:C	F57L	0.985
6:31616120:T:A	F57L	0.985
6:31616120:T:G	F57L	0.985
6:31616392:C:T	T82I	0.981
6:31616390:G:C	K81N	0.980
6:31616390:G:T	K81N	0.980
6:31616368:T:C	L74P	0.979
6:31616467:T:A	L107H	0.979
6:31616464:T:C	F106S	0.977
6:31616467:T:C	L107P	0.977
6:31616818:T:C	I121T	0.977
6:31616110:A:C	Y54S	0.976
6:31616358:A:G	K71E	0.976
6:31615532:T:C	F13L	0.971
6:31615534:C:A	F13L	0.971
6:31615534:C:G	F13L	0.971
6:31616394:C:G	H83D	0.971
6:31616396:C:A	H83Q	0.971

dbSNP variants (sampled 300 via entrez): RS1000047016 (6:31617322 T>C), RS1001749810 (6:31613751 C>T), RS1001830310 (6:31613393 C>A,T), RS1002768367 (6:31613570 C>T), RS1003421720 (6:31615583 G>A), RS1003871460 (6:31615085 G>A), RS1003903064 (6:31615150 C>T), RS1004515745 (6:31614515 T>C), RS1005526312 (6:31614762 G>A), RS1006973268 (6:31613705 A>G), RS1008011047 (6:31613835 C>A), RS1008352054 (6:31614209 G>C), RS1010147128 (6:31613943 G>A), RS1011872657 (6:31614152 G>A,T), RS1011973975 (6:31617045 G>A,C)

Disease associations

OMIM: gene MIM:601833 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST000299_1	Weight	2.000000e-08
GCST000738_5	Neonatal lupus	5.000000e-10
GCST001652_9	Crohn’s disease	3.000000e-06
GCST001956_32	Height	3.000000e-10
GCST002597_1	Laryngeal squamous cell carcinoma	2.000000e-15
GCST003858_9	Oral cavity cancer	7.000000e-08
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_281	Autism spectrum disorder or schizophrenia	5.000000e-09
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST005038_108	Allergic disease (asthma, hay fever or eczema)	9.000000e-16
GCST005542_1	Sarcoidosis (non-Lofgren’s syndrome without extrapulmonary manifestations)	7.000000e-06
GCST005790_61	Rosacea symptom severity	3.000000e-12
GCST006575_36	Takayasu arteritis	1.000000e-09
GCST006979_500	Heel bone mineral density	2.000000e-09
GCST008916_111	Asthma	2.000000e-14
GCST008916_114	Asthma	1.000000e-09
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight
EFO:0009180	rosacea severity measurement
EFO:0009270	heel bone mineral density
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004980	appendicular lean mass
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
Tretinoin	increases expression	2
triphenyl phosphate	affects expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium bichromate	decreases expression	1
quinoline	increases activity	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
mepanipyrim	increases reaction, affects cotreatment, increases expression	1
pyrimethanil	affects cotreatment, increases expression, increases reaction	1
cyprodinil	affects cotreatment, increases expression, increases reaction	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
trans-10,cis-12-conjugated linoleic acid	decreases expression	1
physalin A	increases expression	1
Arsenic Trioxide	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Diuron	decreases expression	1
Menthol	increases expression	1
Nickel	increases expression	1
Sodium Dodecyl Sulfate	affects response to substance	1
Tetrachlorodibenzodioxin	decreases expression, increases expression	1
Aflatoxin B1	decreases expression	1
Medroxyprogesterone Acetate	increases expression	1
Uranium Compounds	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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