IL34

Summary

IL34 (interleukin 34, HGNC:28529) is a protein-coding gene on chromosome 16q22.1, encoding Interleukin-34 (Q6ZMJ4). Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages.

Interleukin-34 is a cytokine that promotes the differentiation and viability of monocytes and macrophages through the colony-stimulating factor-1 receptor (CSF1R; MIM 164770) (Lin et al., 2008 [PubMed 18467591]).

Source: NCBI Gene 146433 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_001393494

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28529
Approved symbol	IL34
Name	interleukin 34
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC34647, IL-34
Ensembl gene	ENSG00000157368
Ensembl biotype	protein_coding
OMIM	612081
Entrez	146433

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000288098, ENST00000429149, ENST00000566361, ENST00000569641, ENST00000574181, ENST00000877106, ENST00000877107, ENST00000877108, ENST00000877109, ENST00000877110, ENST00000913509, ENST00000913510, ENST00000913511, ENST00000913512, ENST00000953393, ENST00000953394, ENST00000953395

RefSeq mRNA: 9 — MANE Select: NM_001393494 NM_001172771, NM_001172772, NM_001393493, NM_001393494, NM_001393495, NM_001393496, NM_001393497, NM_001393498, NM_152456

CCDS: CCDS10895, CCDS92192

Canonical transcript exons

ENST00000288098 — 6 exons

Exon	Start	End
ENSE00001032153	70656960	70657121
ENSE00001032159	70659618	70659753
ENSE00001250984	70646559	70646975
ENSE00001881912	70659997	70660682
ENSE00003648596	70656602	70656679
ENSE00003786987	70654538	70654671

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 96.18.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1881 / max 61.0669, expressed in 230 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154894	0.5594	102
154889	0.4499	145
154895	0.1443	63
154893	0.0132	3
154896	0.0117	6
154890	0.0095	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	96.18	gold quality
upper arm skin	UBERON:0004263	95.91	silver quality
kidney epithelium	UBERON:0004819	95.78	silver quality
spleen	UBERON:0002106	95.41	gold quality
lower esophagus mucosa	UBERON:0035834	94.86	gold quality
skin of abdomen	UBERON:0001416	93.40	gold quality
skin of leg	UBERON:0001511	92.87	gold quality
left ventricle myocardium	UBERON:0006566	92.30	silver quality
sural nerve	UBERON:0015488	92.15	gold quality
parotid gland	UBERON:0001831	91.50	silver quality
vena cava	UBERON:0004087	90.92	silver quality
pancreatic ductal cell	CL:0002079	90.83	silver quality
zone of skin	UBERON:0000014	90.59	gold quality
epithelial cell of pancreas	CL:0000083	90.33	silver quality
buccal mucosa cell	CL:0002336	89.65	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.43	silver quality
cardiac muscle of right atrium	UBERON:0003379	89.21	gold quality
cerebellar vermis	UBERON:0004720	89.17	silver quality
tendon of biceps brachii	UBERON:0008188	88.56	silver quality
right coronary artery	UBERON:0001625	88.48	gold quality
ascending aorta	UBERON:0001496	87.85	gold quality
thoracic aorta	UBERON:0001515	87.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.59	gold quality
body of tongue	UBERON:0011876	87.37	silver quality
pons	UBERON:0000988	86.10	gold quality
prefrontal cortex	UBERON:0000451	85.94	gold quality
descending thoracic aorta	UBERON:0002345	85.93	gold quality
left adrenal gland cortex	UBERON:0035825	85.75	gold quality
adrenal cortex	UBERON:0001235	85.67	gold quality
pylorus	UBERON:0001166	85.39	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-53	no	19.05
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CCL2	Activation
ITGAX	Activation

Upstream regulators (CollecTRI, top): SPI1

miRNA regulators (miRDB)

12 targeting IL34, 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-6077	99.99	68.04	2299
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-4640-3P	94.58	63.02	263

Literature-anchored findings (GeneRIF, showing 40)

• Discovered IL-34 and its receptor CSF1 by functional screening of the extracellular proteome. (PMID:18467591)
• The different spatiotemporal expression of IL-34 and CSF-1 allows for complementary activation of the CSF-1R in developing and adult tissues. (PMID:20504948)
• study identifies IL-34 expression in the synovial tissue of patients with arthritis; this cytokine, as a downstream effector of TNFalpha and IL-1beta, may contribute to inflammation and bone erosions in rheumatoid arthritis (PMID:22039170)
• Data suggest a discrete role of IL-34 in inflammatory rheumatoid arthritis (RA) diseases. (PMID:22264405)
• IL-34 as a nonredundant cytokine for the development of Langerhans cells during embryogenesis as well as for their homeostasis in the adult skin. (PMID:23177320)
• IL-34 levels were significantly increased in patients with coronary artery disease (CAD), and positively correlated with hs-CRP levels, suggesting that IL-34 may be an independent predictor of CAD. (PMID:23206468)
• the feline CSF-1R was cloned and the responsiveness to CSF-1 and IL-34 from a range of species, was examined. (PMID:23260168)
• These findings suggest that IL-34 may play a role in the pathogenesis of rheumatoid arthritis. (PMID:23421370)
• This study is the first to illustrate downstream transcriptional profiles and pathways of IL-34 in comparison with CSF-1 and identify notable differences in CCR2 expression. (PMID:23684409)
• Data suggest that CSF-1R-independent actions of IL-34 via receptor-type protein-tyrosine phosphatase zeta (PTP-zeta) might be considered in evaluating IL-34 roles in development and disease. (PMID:23744080)
• Circulating IL-34 levels in rheumatoid arthritis correlated with autoantibody production. (PMID:23996288)
• IL-34 expression in human gingival fibroblasts, stimulated by TNF-alpha and IL-1beta (PMID:24339952)
• IL-34 is associated with insulin resistance. (PMID:24712570)
• IL-34 promotes the development, survival, and function of microglia and Langerhans cells; therefore, this cytokine may predominately function in brain and skin biology.[review] (PMID:24737461)
• These results suggest that IL-34, a novel osteoclastogenic cytokine, plays a role in rheumatoid arthritis-associated joint damage and is a potential biomarker for predicting subsequent radiographic progression in patients with RA. (PMID:25027626)
• potent profibrotic factor in hepatitis C virus liver fibrosis (PMID:25066464)
• IL-34 is induced by IL-22 in the inflammatory cascade in response to IAV infection. (PMID:25415279)
• In vitro and in vivo experiments indicate that IL-34 expression is regulated by TNF-a and IL-1b and that its overexpression is associated with an increase in osteosarcoma growth and metastasis. (PMID:25471534)
• This paper provides evidence of alternative binding of IL-34 to chondroitin sulphates and syndecan-1 at the cell surface that modulates M-CSFR activation. (PMID:25662098)
• IL-34 is up-regulated in inflammatory bowel disease and suggest a role for this cytokine in sustaining the inflammatory responses in this disease (PMID:25800277)
• the expression pattern of IL-34 in ileum and colon and suggest IL-34 as a new modulator of inflammation in inflammatory bowel disease (PMID:25896238)
• findings demonstrated that M-CSF binds to IL-34; molecular docking studies predicted the formation of a heteromeric M-CSF/IL-34 cytokine (PMID:26095744)
• IL-34 is expressed by human FOXP3+CD45RCloCD8+ and CD4+ Tregs and markedly inhibited alloreactive immune responses. (PMID:26389674)
• miR-28-5p-IL-34-macrophage feedback loop modulates hepatocellular carcinoma metastasis (PMID:26754294)
• The receiver operating characteristic (ROC) curve analysis has shown that IL-34 has more discriminatory power than C-reactive protein (CRP) for the risk of diabetic complications. The cut-off value for IL-34 was established as 91.2 pg/mL. The gist of our research was identification of IL-34 as an additional potential inflammatory biomarker for the prediction of the risk of vascular diabetic complications. (PMID:26849008)
• The IL-34/STAT3/miR-21 pathway is crucial for the survival of synovial fibroblasts in rheumatoid arthritis (PMID:27084907)
• Data indicate that the interleukin 34 (IL-34) is a feasible diagnostic marker of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) patients. (PMID:27363523)
• pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. (PMID:27550451)
• The current study aimed to assess the IL-34 expression in response to two members of the transforming growth factor (TGF)-beta family, TGF-beta1 and bone morphogenetic protein (BMP)-2, in synovial fibroblasts from rheumatoid arthritis patients. (PMID:27865758)
• In conclusion, elevated serum IL-34 levels were demonstrated to be independently associated with renal insufficiency and coronary artery disease in patients with chronic heart failure, regardless of the systolic function. (PMID:27982136)
• Data show that both serum interleukin-34 (IL-34) and IL-34 mRNA in mononuclear leukocytes (PBMCs) in chronic hepatitis B virus (HBV) patients was significantly decreased compared to the healthy controls. (PMID:28614380)
• Findings uncover a novel function for IKKbeta/mHTTx1 interactions in regulating IL-34 production, and implicate a role for IL-34 in non-cell-autonomous, microglial-dependent neurodegeneration in HD. (PMID:28973132)
• Data showed that single expression of M-CSF or IL-34 can be observed in lung cancer tissues and correlated with poor survival. Additionally, their high co-expression correlates with disease stages and poor survival. Thus, evaluating the expression of both M-CSF and IL-34 may help to estimate disease progression and malignant degree in lung cancer patients. (PMID:29323162)
• Systemic Lupus Erythematosus (SLE) patients with detectable IL-34 levels had higher SLE Disease Activity Index (SLEDAI) and IgG concentrations and lower C3 and Hb levels than patients with undetectable IL-34 levels. Therefore, IL-34 could be a potential disease activity marker for SLE. (PMID:29472590)
• Our study shows that IL-34 is produced at the fetal-maternal interface by both placental cyto- and syncytiotrophoblasts and decidual stromal cells. (PMID:29579271)
• Study indicates that IL-34 can be an indicator of liver inflammation and fibrosis in patients with chronic hepatitis B virus infection. (PMID:29599606)
• this study shows that IL-34 regulates IL-6 and IL-8 production in human lung fibroblasts via MAPK, PI3K-Akt, JAK and NF-kappaB signaling pathways (PMID:29857241)
• Increased serum IL-34 levels were associated with greater frequency and severity of interstitial lung disease in systemic sclerosis patients. (PMID:30004593)
• Using a small amount of peripheral blood,successfully detected possible neuron-derived exosome-related blood biomarkers. This is the first study to suggest that not only SYP and TNFR1 but also IL34 are important blood biomarkers for patients with Manic Depressive Disorder. (PMID:30059939)
• Study found that high IL-34 levels in synovial fluid were significantly associated with the radiographic and symptomatic severity of knee osteoarthritis. (PMID:30159102)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il34	ENSMUSG00000031750
rattus_norvegicus	Il34	ENSRNOG00000017602

Protein

Protein identifiers

Interleukin-34 — Q6ZMJ4 (reviewed: Q6ZMJ4)

All UniProt accessions (2): J3QQT3, Q6ZMJ4

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of pro-inflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.

Subunit / interactions. Homodimer. Interacts with CSF1R.

Subcellular location. Secreted.

Tissue specificity. Detected in the sinusoidal epithelium in the red pulp of spleen (at protein level). Predominantly expressed in spleen. Also detected in a range of other tissues including heart, brain, lung, liver, kidney, thymus, testis, ovary, small intestine, prostate and colon.

Similarity. Belongs to the IL-34 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZMJ4-1	1	yes
Q6ZMJ4-2	2

RefSeq proteins (9): NP_001166242, NP_001166243, NP_001380422, NP_001380423, NP_001380424, NP_001380425, NP_001380426, NP_001380427, NP_689669 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020415	IL-34	Family
IPR038328	IL-34_sf	Homologous_superfamily

Pfam: PF15036

UniProt features (23 total): helix 8, turn 4, strand 3, sequence variant 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4DKC	X-RAY DIFFRACTION	1.85
4DKF	X-RAY DIFFRACTION	2.61
4DKD	X-RAY DIFFRACTION	3
4DKE	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMJ4-F1	80.45	0.65

Antibody-complex structures (SAbDab): 2 — 4DKE, 4DKF

Functional residue map

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

Glycosylation sites (1): 76

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-449836	Other interleukin signaling
R-HSA-9680350	Signaling by CSF1 (M-CSF) in myeloid cells

MSigDB gene sets: 182 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, chr16q22, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEUROGENESIS, GOMF_GROWTH_FACTOR_ACTIVITY

GO Biological Process (19): positive regulation of protein phosphorylation (GO:0001934), inflammatory response (GO:0006954), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), positive regulation of macrophage chemotaxis (GO:0010759), positive regulation of MAPK cascade (GO:0043410), innate immune response (GO:0045087), positive regulation of macrophage differentiation (GO:0045651), positive regulation of monocyte differentiation (GO:0045657), positive regulation of oligodendrocyte differentiation (GO:0048714), interleukin-34-mediated signaling pathway (GO:0061514), microglial cell proliferation (GO:0061518), positive regulation of macrophage proliferation (GO:0120041), immune system process (GO:0002376), signal transduction (GO:0007165), positive regulation of macromolecule metabolic process (GO:0010604), positive regulation of cell development (GO:0010720), positive regulation of multicellular organismal process (GO:0051240), regulation of multicellular organismal development (GO:2000026)

GO Molecular Function (5): cytokine activity (GO:0005125), macrophage colony-stimulating factor receptor binding (GO:0005157), growth factor activity (GO:0008083), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of myeloid leukocyte differentiation	2
macrophage proliferation	2
regulation of multicellular organismal process	2
receptor ligand activity	2
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	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 gene expression	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
macrophage differentiation	1
regulation of macrophage differentiation	1
monocyte differentiation	1
regulation of monocyte differentiation	1
positive regulation of glial cell differentiation	1
oligodendrocyte differentiation	1
regulation of oligodendrocyte differentiation	1
cytokine-mediated signaling pathway	1
glial cell proliferation	1
positive regulation of leukocyte proliferation	1
regulation of macrophage proliferation	1
biological_process	1
cell communication	1
cellular process	1
signaling	1

Protein interactions and networks

STRING

1161 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL34	CSF1R	P07333	998
IL34	CSF1	P09603	976
IL34	SDC1	P18827	835
IL34	CX3CR1	P49238	752
IL34	PTPRZ1	P23471	668
IL34	TREM2	Q9NZC2	654
IL34	TMEM119	Q4V9L6	605
IL34	PTPRC	P08575	603
IL34	CSF2	P04141	561
IL34	CX3CL1	P78423	543
IL34	CD163	Q86VB7	538
IL34	SPI1	P17947	533
IL34	IL10	P22301	526
IL34	P2RY12	Q9H244	520
IL34	CD200	P41217	518

IntAct

5 interactions, top by confidence:

A	B	Type	Score
LCE1F	IL34	psi-mi:“MI:0915”(physical association)	0.560
IL34	LCE1F	psi-mi:“MI:0915”(physical association)	0.000
ATXN1	IL34	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): IL34 (Reconstituted Complex), LCE1F (Two-hybrid), IL34 (Two-hybrid)

ESM2 similar proteins: A0A2R8QHQ6, A0A3Q1LRJ2, A0A8M9PDM1, A6QL48, B4ER10, E9Q8Q8, O02720, O46673, O70615, P01244, P01245, P01246, P01248, P06880, P0DJF3, P19795, P33711, P37886, P46404, P46407, P48411, P56437, Q13007, Q1HFN3, Q1XG29, Q29406, Q3KNT9, Q4KM46, Q62575, Q659Q8, Q6AYE5, Q6UXV1, Q6ZMJ4, Q71SY6, Q7YQB8, Q7YQD2, Q7YRR6, Q864S7, Q86UD1, Q8HYE5

Diamond homologs: A6QL48, Q4KM46, Q6ZMJ4, Q8R1R4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IL34	“up-regulates activity”	CSF1R	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1896 predictions. Top by Δscore:

Variant	Effect	Δscore
16:70646658:G:GT	donor_gain	1.0000
16:70654665:G:GG	donor_gain	1.0000
16:70656597:TCCAG:T	acceptor_loss	1.0000
16:70656598:CCAGA:C	acceptor_loss	1.0000
16:70656599:CAGAA:C	acceptor_loss	1.0000
16:70656600:A:AG	acceptor_gain	1.0000
16:70656600:A:C	acceptor_loss	1.0000
16:70656601:G:GA	acceptor_gain	1.0000
16:70656601:GA:G	acceptor_gain	1.0000
16:70656601:GAA:G	acceptor_gain	1.0000
16:70656601:GAAA:G	acceptor_gain	1.0000
16:70656601:GAAAC:G	acceptor_gain	1.0000
16:70656676:GCTG:G	donor_gain	1.0000
16:70656954:CCGCA:C	acceptor_loss	1.0000
16:70656955:CGCA:C	acceptor_loss	1.0000
16:70656956:GCAG:G	acceptor_loss	1.0000
16:70656957:CAGC:C	acceptor_loss	1.0000
16:70656958:A:AG	acceptor_gain	1.0000
16:70656959:G:GG	acceptor_gain	1.0000
16:70656959:GC:G	acceptor_gain	1.0000
16:70656959:GCA:G	acceptor_gain	1.0000
16:70656959:GCAGA:G	acceptor_gain	1.0000
16:70657120:CG:C	donor_gain	1.0000
16:70657121:GG:G	donor_gain	1.0000
16:70657121:GGT:G	donor_loss	1.0000
16:70657122:G:A	donor_loss	1.0000
16:70657122:G:GG	donor_gain	1.0000
16:70657123:T:A	donor_loss	1.0000
16:70659616:A:AC	acceptor_loss	1.0000
16:70659616:A:AG	acceptor_gain	1.0000

AlphaMissense

1552 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:70656999:T:A	W94R	0.996
16:70656999:T:C	W94R	0.996
16:70657011:A:C	S98R	0.996
16:70657013:C:A	S98R	0.996
16:70657013:C:G	S98R	0.996
16:70659701:A:C	K162N	0.995
16:70659701:A:T	K162N	0.995
16:70657001:G:C	W94C	0.994
16:70657001:G:T	W94C	0.994
16:70659712:A:T	D166V	0.993
16:70659697:C:A	P161H	0.992
16:70659700:A:T	K162I	0.991
16:70654643:T:C	L45P	0.990
16:70656658:A:C	R73S	0.990
16:70656658:A:T	R73S	0.990
16:70659711:G:C	D166H	0.990
16:70660022:G:C	W188C	0.990
16:70660022:G:T	W188C	0.990
16:70656612:T:C	F58S	0.989
16:70659712:A:C	D166A	0.989
16:70659716:C:A	N167K	0.989
16:70659716:C:G	N167K	0.989
16:70659717:T:C	C168R	0.989
16:70656612:T:G	F58C	0.988
16:70657058:C:A	H113Q	0.988
16:70657058:C:G	H113Q	0.988
16:70654657:C:G	R50G	0.985
16:70657057:A:G	H113R	0.984
16:70659696:C:T	P161S	0.984
16:70659697:C:G	P161R	0.984

dbSNP variants (sampled 300 via entrez): RS1000016773 (16:70644894 G>A,C), RS1000024057 (16:70588711 A>G), RS1000102642 (16:70638090 G>A), RS1000134704 (16:70628148 A>C), RS1000209567 (16:70622816 G>A,C), RS1000231950 (16:70610404 T>C), RS1000247724 (16:70600670 T>C), RS1000251735 (16:70583060 G>A), RS1000295280 (16:70632295 G>T), RS1000311434 (16:70595281 C>A,G), RS1000376453 (16:70636023 C>G,T), RS1000382387 (16:70624619 C>G), RS1000408068 (16:70622684 G>A), RS1000452575 (16:70606659 C>G), RS1000469754 (16:70624317 G>A)

Disease associations

OMIM: gene MIM:612081 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004070_7	Cerebrospinal P-tau181p levels	8.000000e-06
GCST005553_1	Diffuse cutaneous systemic sclerosis	1.000000e-06
GCST006394_79	Intraocular pressure	7.000000e-09
GCST006412_93	Intraocular pressure	3.000000e-08
GCST006993_12	Hippocampal volume in Alzheimer’s disease dementia	1.000000e-07
GCST010703_100	Brain morphology (MOSTest)	2.000000e-40
GCST010725_47	Malaria	6.000000e-07
GCST010989_16	Body size at age 10	4.000000e-10
GCST012182_8	Alzheimer’s disease	4.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004763	p-tau measurement
EFO:0004695	intraocular pressure measurement
EFO:0005035	hippocampal volume
EFO:0004346	neuroimaging measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Nickel	decreases expression	2
Asian ginseng	decreases expression, decreases reaction, affects cotreatment	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
terbufos	increases methylation	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
abrine	increases expression	1
eprenetapopt	affects expression, affects reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Calcitriol	increases expression	1
Diethylhexyl Phthalate	decreases expression, decreases reaction, affects cotreatment	1
Fonofos	increases methylation	1
Estradiol	decreases expression	1
Lead	affects expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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