LIF

Summary

LIF (LIF interleukin 6 family cytokine, HGNC:6596) is a protein-coding gene on chromosome 22q12.2, encoding Leukemia inhibitory factor (P15018). LIF has the capacity to induce terminal differentiation in leukemic cells.

The protein encoded by this gene is a pleiotropic cytokine with roles in several different systems. It is involved in the induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, regulator of mesenchymal to epithelial conversion during kidney development, and may also have a role in immune tolerance at the maternal-fetal interface. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 3976 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_002309

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6596
Approved symbol	LIF
Name	LIF interleukin 6 family cytokine
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	CDF, DIA, HILDA
Ensembl gene	ENSG00000128342
Ensembl biotype	protein_coding
OMIM	159540
Entrez	3976

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000249075, ENST00000403987

RefSeq mRNA: 2 — MANE Select: NM_002309 NM_001257135, NM_002309

CCDS: CCDS13872, CCDS58799

Canonical transcript exons

ENST00000249075 — 3 exons

Exon	Start	End
ENSE00000879785	30244755	30244933
ENSE00001215846	30240453	30244061
ENSE00001551728	30246677	30246759

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 96.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.2565 / max 1001.3120, expressed in 1140 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193579	26.2632	1118
193580	0.8256	340
193581	0.1677	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	96.89	gold quality
gall bladder	UBERON:0002110	93.56	gold quality
type B pancreatic cell	CL:0000169	91.69	silver quality
islet of Langerhans	UBERON:0000006	90.17	gold quality
vena cava	UBERON:0004087	87.67	gold quality
olfactory bulb	UBERON:0002264	86.57	gold quality
epithelial cell of pancreas	CL:0000083	85.06	silver quality
mucosa of urinary bladder	UBERON:0001259	84.94	gold quality
cervix squamous epithelium	UBERON:0006922	84.60	gold quality
tongue squamous epithelium	UBERON:0006919	83.54	gold quality
vermiform appendix	UBERON:0001154	81.37	gold quality
pancreatic ductal cell	CL:0002079	80.57	silver quality
omental fat pad	UBERON:0010414	80.00	gold quality
peritoneum	UBERON:0002358	79.96	gold quality
caecum	UBERON:0001153	78.83	gold quality
mucosa of transverse colon	UBERON:0004991	78.50	gold quality
adipose tissue of abdominal region	UBERON:0007808	78.07	gold quality
smooth muscle tissue	UBERON:0001135	77.91	gold quality
mucosa of paranasal sinus	UBERON:0005030	77.61	silver quality
upper lobe of left lung	UBERON:0008952	77.51	gold quality
rectum	UBERON:0001052	76.60	gold quality
upper lobe of lung	UBERON:0008948	76.37	gold quality
cervix epithelium	UBERON:0004801	76.07	gold quality
left uterine tube	UBERON:0001303	75.78	gold quality
transverse colon	UBERON:0001157	75.66	gold quality
adenohypophysis	UBERON:0002196	75.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.18	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.85	gold quality
upper leg skin	UBERON:0004262	74.70	gold quality
small intestine	UBERON:0002108	73.95	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.94
E-MTAB-9801	yes	5.98
E-MTAB-6678	yes	4.84
E-GEOD-70580	no	514.88
E-GEOD-86618	no	111.94

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
MYH7	Activation

Upstream regulators (CollecTRI, top): ATF3, EGR2, FOSL2, FOXC1, FOXP3, HSF4, JUN, MYCN, NFATC1, NODAL, PAX1, PGR, STAT3, STAT5A, TP53, TXK

miRNA regulators (miRDB)

129 targeting LIF, 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-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
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-6077	99.99	68.04	2299
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-579-3P	99.86	71.66	3628

Literature-anchored findings (GeneRIF, showing 40)

• LIF stimulates proliferation of rat pituitary tumor cells in culture, inhibits secretion of prolactin and growth hormone and induces tyrosine phosphorylation of STAT3 in the cells. (PMID:11448119)
• The entire structure of the LIF gene of 48 alleles in the Japanese population was sequenced. (PMID:11587067)
• Oncostatin M and leukemia inhibitory factor regulate the growth of normal human breast epithelial cells (PMID:11811789)
• LIF does not activate STAT3, ERK, or gp130 receptor in human N tera-2/D1 EC cells. The suppressor of cytokine signaling 1 (SOCS-1) is constitutively expressed, suggesting that LIF signal transduction is inhibited by elevated levels of SOCS-1 expression. (PMID:11855863)
• experimental N-Myc overexpression results in down-regulation of leukemia inhibitory factor (LIF), a modulator of endothelial cell proliferation (PMID:12153570)
• LIF stimulates (45)Ca release and enhances expression of receptor activator of NF-kappa B ligand (RANKL) and osteoprotegerin in neonatal mouse calvarial cultures, but has no effect on the expression of RANK. (PMID:12218157)
• role for LIF in loss of autocrine prolactin suppression contributing to unrestrained prolactinomas prolactin secretion. (PMID:12574225)
• LIF regulates cell survival of normal human endometrial stromal cells dose-dependently. (PMID:12579339)
• Leukemia inhibitory factor (LIF), cardiotrophin-1, and oncostatin M share structural binding determinants in the immunoglobulin-like domain of LIF receptor (PMID:12707269)
• LIF has a role in src family kinase-independent signal transduction and gene induction (PMID:12764151)
• Leukemia inhibitory factor (LIF) increased overall expansion of human neural precursor cells grown in culture; Following LIF withdrawal, 200 genes showed significant decreases (PMID:12807438)
• binding of ETS transcription factors to the ETS binding sites in the human LIF promoter is critical for its inducibility in response to T cell activators and play an important functional role within the endocrine-immune network. (PMID:14557674)
• role in hepatocyte growth factor expression (PMID:14647442)
• Decreased concentartion of LIF in infertile women do not seem to have a genetic basis due to the low frequency of LIF gene alterations. (PMID:14687743)
• Constitutive expression of cytokines in brain induces changes in gene expression characteristic of chronic inflammation leading to either temporal weight reduction (CNTF) or severe cachexia (leukemia inhibitory factor). (PMID:14715713)
• immunocytochemical staining and mRNA expression of LIF and its receptor are consistent with the concept that LIF might be involved in growth initiation of primordial follicles through its receptor (PMID:15044601)
• At early human post-implantation stage, LIF is produced from decidua and chorionic villi and may exert its action on trophoblasts. Anembryonic pregnancy cannot be accounted for by defective expression of either LIF or LIF-Rbeta in most circumstances. (PMID:15180980)
• Both IL-6 and LIF can be very efficiently induced by IL-1beta in articular chondrocytes in vitro, more so in osteosarthritis than in normal cells. (PMID:15341921)
• LIFRbeta and the signaling subunit gp130 are expressed in hESCs and human LIF can induce STAT3 phosphorylation and nuclear translocation in hESCs. (PMID:15342941)
• LCH represents a cytokine-driven condition partially mediated by TNF, IL-11, and LIF. These three cytokines are all osteoclastogenic, suggesting a pathogenetic pathway for the osteolytic lesions in LCH. (PMID:15543003)
• These results indicated that LIF induced multi-lineage differentiation of adult stem-like cells in kidney via cadherin 16. (PMID:15670782)
• role of leukemia inhibitory factor (LIF) and its receptors in human embryo implantation (PMID:15731310)
• demonstrate using RNAi that Stat3 activation is necessary in the invasive phenotype of trophoblast cells and can be controlled via Leukemia Inhibitory Factor (LIF) (PMID:15837065)
• different members of the TGF-beta superfamily may also contribute in the reproductive process by enhancing endometrial proimplantatory LIF secretion and reducing proinflammatory IL-6 release by endometrial epithelium (PMID:15905624)
• LIF plays an essential role in the preimplantation embryo development and the blastocyst implantation and its gene mutations in women contribute to the implantation failure and subsequent infertility. (PMID:16295654)
• Leukemia inhibitory factor concentration in follicular fluid is not a useful marker for the prediction of number and quality of embryos, or implantation and pregnancy rates. (PMID:16341766)
• Data show that increased leukemia inhibitory factor secretion enhances airway reactivity and intracellular calcium signaling. (PMID:16489116)
• results suggest that the LIF gene mutations affect fertility (PMID:16545901)
• Since we demonstrated that not only SDF-1, but also HGF and LIF are upregulated in damaged tissues, we postulate that CXCR4+ c-Met+ LIF-R+ TCSC could be mobilized from the BM into the PB, where they play a role in tissue repair/regeneration. (PMID:16648972)
• Down-regulation of PRB in the endometrium is concomitant with the presence of glycodelin in the endometrium, suggesting interaction. (PMID:16759928)
• Suppressor of cytokine signaling-1 may prevent leukemia inhibitory factor signaling in human embryonic stem cells. (PMID:16949591)
• There is no receptivity defect with regard to LIF and IL-11 secretions by eutopic endometrium in infertile women with endometriosis. (PMID:17000646)
• Ciliary neurotrophic factor/LIF signaling pathway acts via regulation of nitric oxide production to modulate developmental programmed cell death of postmitotic rod precursor cells. (PMID:17054938)
• The regulation of LIF and its receptor (LIFR) expression in pancreatic carcinoma cells were studied. (PMID:17332938)
• provides a structural template to understand the formation and orientation of the high-affinity signaling complex between LIF, LIF receptor, and gp130 (PMID:17652170)
• interleukin-8 (CXCL-8) is induced by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells (PMID:17671691)
• Endometrial integrin beta3 and LIF expressions in the peri-implantation phase were significantly lower in stimulated cycles (including both moderate and high responders) compared to natural controls. (PMID:17681328)
• LIF and IL6 skew monocyte differentiation into tumor-associated macrophage (TAM)-like cells by enabling monocytes to consume monocyte-CSF. Depletion of LIF, IL-6, and M-CSF in ovarian cancer ascites suppressed TAM-like cell induction (PMID:17848619)
• the LIF gene mutation, the heterozygote G to A transition on the position 3400, affects fertility but the infertility treatment can succeed. (PMID:17966612)
• Increased expression of some IL-6 cytokine family members (oncostatin M, gp130, CT-1, LIF) in cutaneous inflammation might contribute to the promotion of hair loss. (PMID:17979974)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lif	ENSMUSG00000034394
rattus_norvegicus	Lif	ENSRNOG00000007002

Protein

Protein identifiers

Leukemia inhibitory factor — P15018 (reviewed: P15018)

Alternative names: Differentiation-stimulating factor, Melanoma-derived LPL inhibitor

All UniProt accessions (1): P15018

UniProt curated annotations — full annotation on UniProt →

Function. LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes.

Subcellular location. Secreted.

Similarity. Belongs to the LIF/OSM family.

Isoforms (2)

UniProt ID	Names	Canonical?
P15018-1	1	yes
P15018-2	2

RefSeq proteins (2): NP_001244064, NP_002300* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001581	Leukemia_IF/oncostatin	Family
IPR003624	Leukemia_IF	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR019827	Leukemia_IF/oncostatin_CS	Conserved_site

Pfam: PF01291

UniProt features (22 total): glycosylation site 6, helix 5, disulfide bond 3, strand 3, splice variant 2, signal peptide 1, chain 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1PVH	X-RAY DIFFRACTION	2.5
7N0A	X-RAY DIFFRACTION	3.1
1EMR	X-RAY DIFFRACTION	3.5
8D6A	ELECTRON MICROSCOPY	3.54
2Q7N	X-RAY DIFFRACTION	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15018-F1	87.55	0.76

Antibody-complex structures (SAbDab): 1 — 7N0A

Functional residue map

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

Disulfide bonds (3): 82–185, 34–156, 40–153

Glycosylation sites (6): 31, 56, 85, 95, 118, 138

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-6783783	Interleukin-10 signaling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-6788467	IL-6-type cytokine receptor ligand interactions
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-449147	Signaling by Interleukins
R-HSA-6783589	Interleukin-6 family signaling

MSigDB gene sets: 520 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TGGTGCT_MIR29A_MIR29B_MIR29C, AGGAAGC_MIR5163P, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, MODULE_52, MODULE_92, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, RRAGTTGT_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP

GO Biological Process (46): cell morphogenesis (GO:0000902), response to hypoxia (GO:0001666), blood vessel remodeling (GO:0001974), immune response (GO:0006955), embryo implantation (GO:0007566), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), macrophage differentiation (GO:0030225), positive regulation of peptidyl-serine phosphorylation (GO:0033138), positive regulation of cell adhesion mediated by integrin (GO:0033630), somatic stem cell population maintenance (GO:0035019), positive regulation of MAPK cascade (GO:0043410), regulation of cell differentiation (GO:0045595), positive regulation of macrophage differentiation (GO:0045651), negative regulation of meiotic nuclear division (GO:0045835), positive regulation of transcription by RNA polymerase II (GO:0045944), decidualization (GO:0046697), negative regulation of hormone secretion (GO:0046888), fibroblast proliferation (GO:0048144), positive regulation of fibroblast proliferation (GO:0048146), lung alveolus development (GO:0048286), muscle organ morphogenesis (GO:0048644), neuron development (GO:0048666), positive regulation of astrocyte differentiation (GO:0048711), leukemia inhibitory factor signaling pathway (GO:0048861), stem cell differentiation (GO:0048863), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), lung vasculature development (GO:0060426), lung lobe morphogenesis (GO:0060463), trophoblast giant cell differentiation (GO:0060707), negative regulation of ERK1 and ERK2 cascade (GO:0070373), positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis (GO:0072108), regulation of metanephric nephron tubule epithelial cell differentiation (GO:0072307), cell surface receptor signaling pathway via STAT (GO:0097696), meiotic nuclear division (GO:0140013), positive regulation of receptor signaling pathway via STAT (GO:1904894), cell population proliferation (GO:0008283), regulation of cell communication (GO:0010646)

GO Molecular Function (5): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), leukemia inhibitory factor receptor binding (GO:0005146), growth factor activity (GO:0008083), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by Interleukins	3
Interleukin-6 family signaling	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	2
regulation of cell population proliferation	2
receptor ligand activity	2
cellular anatomical structure	2
anatomical structure morphogenesis	1
response to stress	1
response to decreased oxygen levels	1
tissue remodeling	1
immune system process	1
response to stimulus	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
positive regulation of cellular process	1
negative regulation of cellular process	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
positive regulation of protein phosphorylation	1
peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation	1
cell adhesion mediated by integrin	1
regulation of cell adhesion mediated by integrin	1
positive regulation of cell adhesion	1
stem cell population maintenance	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	1
positive regulation of myeloid leukocyte differentiation	1
macrophage differentiation	1
regulation of macrophage differentiation	1
negative regulation of cell cycle process	1
regulation of meiotic nuclear division	1
negative regulation of meiotic cell cycle	1

Protein interactions and networks

STRING

2310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIF	LIFR	P42702	999
LIF	CNTF	P26441	946
LIF	OSM	P13725	929
LIF	IL6ST	P40189	920
LIF	IL11	P20809	918
LIF	POU5F1	P31359	879
LIF	KLF4	P78338	860
LIF	IL6	P05231	858
LIF	CTF1	Q16619	856
LIF	STAT3	P40763	854
LIF	NANOG	Q9H9S0	834
LIF	CNTFR	P26992	832
LIF	FGF2	P09038	828
LIF	OSMR	Q99650	797
LIF	SOX2	P48431	795

IntAct

20 interactions, top by confidence:

A	B	Type	Score
LIF	IL6ST	psi-mi:“MI:0407”(direct interaction)	0.740
IL6ST	LIF	psi-mi:“MI:0915”(physical association)	0.740
LIF	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.560
HPGDS	LIF	psi-mi:“MI:0915”(physical association)	0.560
LIF	NCALD	psi-mi:“MI:0915”(physical association)	0.560
LIF	KRT31	psi-mi:“MI:0915”(physical association)	0.560
LIF	Lifr	psi-mi:“MI:0407”(direct interaction)	0.440
SORT1	LIF	psi-mi:“MI:0407”(direct interaction)	0.440
LIF	LIFR	psi-mi:“MI:0407”(direct interaction)	0.440
LIF	KRT31	psi-mi:“MI:0915”(physical association)	0.000
LIF	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
LIF	HPGDS	psi-mi:“MI:0915”(physical association)	0.000
NCALD	LIF	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): LIF (Reconstituted Complex), LIF (Two-hybrid), LIF (Two-hybrid), HPGDS (Two-hybrid), KRTAP12-3 (Two-hybrid), LIF (Co-localization), LIF (Co-localization), LIF (Affinity Capture-RNA), LIF (Affinity Capture-MS)

ESM2 similar proteins: A0S0B0, A3FBE9, B6CKP4, O62728, P01237, P05231, P08505, P08998, P09056, P09586, P09611, P10766, P11228, P14059, P15018, P16038, P17777, P19795, P20392, P20607, P22077, P33091, P33092, P37884, P37885, P41323, P41683, P43431, P46650, P51494, P79341, Q25BC2, Q27956, Q28819, Q2XNF5, Q4T554, Q5I6E3, Q5IGQ0, Q659Q8, Q6JV22

Diamond homologs: O62728, P09056, P15018, P17777, Q27956

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
LIF	up-regulates	LIFR	binding
NODAL	“up-regulates quantity by expression”	LIF	“transcriptional regulation”
“Activated PSC”	up-regulates	LIF
ZBTB46	“up-regulates quantity by expression”	LIF	“transcriptional regulation”
LIF	up-regulates	IL6ST	binding
LIF	“up-regulates quantity by expression”	MYH7	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

509 predictions. Top by Δscore:

Variant	Effect	Δscore
22:30244058:TGTA:T	acceptor_gain	1.0000
22:30244060:TA:T	acceptor_gain	1.0000
22:30244061:AC:A	acceptor_loss	1.0000
22:30244062:C:CC	acceptor_gain	1.0000
22:30244753:A:AC	donor_gain	1.0000
22:30244754:C:CC	donor_gain	1.0000
22:30244057:GTGTA:G	acceptor_gain	0.9900
22:30244059:GTA:G	acceptor_gain	0.9900
22:30244070:C:CT	acceptor_gain	0.9900
22:30244071:A:T	acceptor_gain	0.9900
22:30244748:AACTT:A	donor_loss	0.9900
22:30244749:ACTT:A	donor_loss	0.9900
22:30244750:CTT:C	donor_loss	0.9900
22:30244751:TTACA:T	donor_loss	0.9900
22:30244752:TACAT:T	donor_loss	0.9900
22:30244753:ACA:A	donor_loss	0.9900
22:30244754:C:A	donor_loss	0.9900
22:30244754:CATA:C	donor_gain	0.9900
22:30246496:TGGG:T	donor_gain	0.9900
22:30244058:TGTAC:T	acceptor_gain	0.9800
22:30244059:G:C	acceptor_gain	0.9800
22:30244059:GTAC:G	acceptor_gain	0.9800
22:30244060:TACT:T	acceptor_gain	0.9800
22:30244061:ACTG:A	acceptor_gain	0.9800
22:30244062:C:CA	acceptor_gain	0.9800
22:30244063:T:A	acceptor_gain	0.9800
22:30244931:CTC:C	acceptor_gain	0.9800
22:30246672:TTTA:T	donor_loss	0.9800
22:30246673:TTACC:T	donor_loss	0.9800
22:30246674:TAC:T	donor_loss	0.9800

AlphaMissense

1320 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:30244039:A:C	F74C	0.995
22:30243707:A:G	C185R	0.993
22:30244015:C:G	C82S	0.992
22:30244015:C:T	C82Y	0.992
22:30244016:A:T	C82S	0.992
22:30243706:C:G	C185S	0.990
22:30243707:A:T	C185S	0.990
22:30244039:A:G	F74S	0.990
22:30244014:A:C	C82W	0.989
22:30244016:A:G	C82R	0.989
22:30243850:A:G	L137P	0.988
22:30243727:A:C	F178C	0.987
22:30244789:A:G	L55P	0.986
22:30243705:A:C	C185W	0.985
22:30243706:C:T	C185Y	0.985
22:30244038:G:C	F74L	0.985
22:30244038:G:T	F74L	0.985
22:30244040:A:G	F74L	0.985
22:30243820:A:G	L147P	0.984
22:30244050:C:A	Q70H	0.984
22:30244050:C:G	Q70H	0.984
22:30243654:G:C	F202L	0.983
22:30243654:G:T	F202L	0.983
22:30243656:A:G	F202L	0.983
22:30244015:C:A	C82F	0.983
22:30243803:A:G	C153R	0.982
22:30243891:C:A	Q123H	0.981
22:30243891:C:G	Q123H	0.981
22:30243946:A:G	L105P	0.981
22:30244798:A:G	L52P	0.981

dbSNP variants (sampled 300 via entrez): RS1000148623 (22:30246739 C>A,T), RS1000161723 (22:30241832 T>A), RS1000803950 (22:30243804 C>T), RS1000867331 (22:30243359 G>A,T), RS1000928675 (22:30240280 C>T), RS1000980798 (22:30246142 AG>A,AGG), RS1001127842 (22:30241017 C>T), RS1001242114 (22:30240681 G>A), RS1001262835 (22:30241357 C>T), RS1002029632 (22:30240010 C>T), RS1002312515 (22:30240206 C>A,T), RS1002436399 (22:30244791 C>A,T), RS1002802931 (22:30242215 A>T), RS1002858152 (22:30244107 C>A,G,T), RS1003104092 (22:30247477 C>A)

Disease associations

OMIM: gene MIM:159540 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000531_1	Inflammatory bowel disease (early onset)	2.000000e-09
GCST001009_3	Nephropathy	2.000000e-09
GCST001725_109	Inflammatory bowel disease	3.000000e-14
GCST003974_1	Tonsillectomy	1.000000e-09
GCST005851_15	Delirium	1.000000e-06
GCST006979_197	Heel bone mineral density	5.000000e-17
GCST009144_10	Disease progression in age-related macular degeneration (adjusted for baseline)	7.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007924	tonsillectomy risk measurement
EFO:0009270	heel bone mineral density
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	10
Tetrachlorodibenzodioxin	increases expression	7
Particulate Matter	increases abundance, increases expression, affects cotreatment	7
Aflatoxin B1	increases expression, affects expression	6
bisphenol A	affects activity, decreases reaction, increases activity, increases reaction, affects expression (+4 more)	5
sodium arsenite	decreases expression, increases expression	5
(+)-JQ1 compound	decreases expression	5
Estradiol	increases activity, affects cotreatment, increases expression, increases phosphorylation, decreases expression (+1 more)	5
Cyclosporine	decreases expression, increases expression	4
tert-Butylhydroperoxide	increases expression, increases methylation	4
Arsenic Trioxide	decreases expression, increases expression	3
Air Pollutants	increases expression, affects cotreatment, decreases expression, increases abundance	3
Cisplatin	affects cotreatment, decreases expression, increases expression	3
Dexamethasone	affects cotreatment, decreases expression	3
Doxorubicin	decreases expression, increases expression	3
Hydrogen Peroxide	affects expression, increases expression	3
Ozone	increases abundance, increases expression, increases oxidation, affects cotreatment, decreases expression	3
Silicon Dioxide	increases expression	3
lasiocarpine	increases expression	2
methyleugenol	increases expression	2
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	2
bisphenol S	decreases expression, increases expression	2
Temozolomide	increases response to substance, increases expression	2
Troglitazone	decreases response to substance, increases expression	2
Azathioprine	increases expression	2
Diethylhexyl Phthalate	increases expression	2
Methotrexate	affects cotreatment, increases expression	2
N-Nitrosopyrrolidine	increases expression	2
Quercetin	increases expression	2
Tetradecanoylphorbol Acetate	affects cotreatment, affects expression, increases expression	2

Cellosaurus cell lines

8 cell lines: 4 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3X1	SEES3-1V human LIF, clone1	Embryonic stem cell	Male
CVCL_A3X2	SEES3-1V human LIF, clone2	Embryonic stem cell	Male
CVCL_A3X3	SEES3-1V human LIF, clone3	Embryonic stem cell	Male
CVCL_B1VS	Abcam HeLa LIF KO	Cancer cell line	Female
CVCL_D7TL	Ubigene A-549 LIF KO	Cancer cell line	Male
CVCL_D8P8	Ubigene HCT 116 LIF KO	Cancer cell line	Male
CVCL_D9IL	Ubigene HEK293 LIF KO	Transformed cell line	Female
CVCL_E0GI	Ubigene HeLa LIF KO	Cancer cell line	Female

Clinical trials (associated diseases)

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