FSTL3

Summary

FSTL3 (follistatin like 3, HGNC:3973) is a protein-coding gene on chromosome 19p13.3, encoding Follistatin-related protein 3 (O95633). Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such as activin, BMP2 and MSTN.

Follistatin-like 3 is a secreted glycoprotein of the follistatin-module-protein family. It may have a role in leukemogenesis.

Source: NCBI Gene 10272 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_005860

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3973
Approved symbol	FSTL3
Name	follistatin like 3
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLRG, FSRP
Ensembl gene	ENSG00000070404
Ensembl biotype	protein_coding
OMIM	605343
Entrez	10272

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000166139, ENST00000588773, ENST00000589185, ENST00000591573, ENST00000592058, ENST00000592947, ENST00000605925, ENST00000905299, ENST00000964202

RefSeq mRNA: 1 — MANE Select: NM_005860 NM_005860

CCDS: CCDS12040

Canonical transcript exons

ENST00000166139 — 5 exons

Exon	Start	End
ENSE00000655234	677792	677977
ENSE00000892310	681650	683385
ENSE00000892311	676392	676526
ENSE00003602279	680274	680489
ENSE00003684051	681333	681560

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 98.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 95.9411 / max 6089.9346, expressed in 1742 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172722	89.9461	1495
172727	3.4063	1192
172726	0.7456	362
172728	0.7304	481
172724	0.4270	190
172734	0.3200	122
172723	0.2112	95
172725	0.1545	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	98.00	gold quality
nerve	UBERON:0001021	97.85	gold quality
tibial nerve	UBERON:0001323	97.85	gold quality
ascending aorta	UBERON:0001496	97.74	gold quality
thoracic aorta	UBERON:0001515	97.70	gold quality
left coronary artery	UBERON:0001626	97.50	gold quality
apex of heart	UBERON:0002098	97.44	gold quality
left adrenal gland cortex	UBERON:0035825	97.33	gold quality
left uterine tube	UBERON:0001303	97.30	gold quality
left adrenal gland	UBERON:0001234	97.15	gold quality
upper lobe of left lung	UBERON:0008952	97.14	gold quality
mucosa of stomach	UBERON:0001199	97.12	gold quality
right adrenal gland	UBERON:0001233	96.98	gold quality
right lung	UBERON:0002167	96.95	gold quality
aorta	UBERON:0000947	96.78	gold quality
right atrium auricular region	UBERON:0006631	96.70	gold quality
right adrenal gland cortex	UBERON:0035827	96.49	gold quality
tibial artery	UBERON:0007610	96.38	gold quality
popliteal artery	UBERON:0002250	96.37	gold quality
coronary artery	UBERON:0001621	96.21	gold quality
descending thoracic aorta	UBERON:0002345	96.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.16	gold quality
lower esophagus	UBERON:0013473	96.08	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.92	gold quality
upper lobe of lung	UBERON:0008948	95.74	gold quality
endocervix	UBERON:0000458	95.73	gold quality
adrenal cortex	UBERON:0001235	95.68	gold quality
right testis	UBERON:0004534	95.13	gold quality
left testis	UBERON:0004533	94.88	gold quality
omental fat pad	UBERON:0010414	94.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	3906.14
E-MTAB-6678	yes	3633.31
E-HCAD-24	yes	2834.30
E-GEOD-135922	yes	19.48
E-ANND-3	yes	10.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB, SMAD3, SMAD4, YAP1

miRNA regulators (miRDB)

61 targeting FSTL3, 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-8485	100.00	77.57	4731
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-485-5P	99.10	64.78	1889

Literature-anchored findings (GeneRIF, showing 40)

• Transcription activation of FLRG and follistatin by activin A, through Smad proteins, participates in a negative feedback loop to modulate activin A function (PMID:11948405)
• our present data suggest that protein kinase C and A signal transduction pathways differently regulate the expression of FLRG in human ovarian granulosa-luteal cells (PMID:12397211)
• Follistatin and FLRG proteins downmodulate the effects of activin A and BMP2 on erythroid maturation. (PMID:12531697)
• likely to be a local regulator of activin action in gonadal development and gametogenesis (PMID:14739256)
• Data report the endometrial mRNA and peptide expression of follistatin-related gene (FLRG), a protein that binds activin-A, preventing its interaction. (PMID:15130517)
• review discusses differences between signal targets of follistatin and FLRG and distinct functions and mechanisms for these two proteins in the human hematopoietic system (PMID:15451575)
• comparison of the kinetics of FST isoform and FSTL3 biosynthesis, trafficking, and secretion (PMID:16150905)
• IGFBP1 and Follistatin-like 3 are highly up-regulated in intrauterine growth restriction in the placenta. (PMID:16338475)
• the differential biological actions among the FST isoforms and FSTL3 are primarily dependent on their relative cell-surface binding ability and ligand specificity (PMID:16627583)
• Follistatin-like 3 expression was low in normal but enhanced in malignant rat liver. in human normal liver, in contrast, it was abundantly expressed but downregulated in liver cancer (PMID:16935389)
• Ovarian endometriotic lesions show a deranged expression of activin A-binding proteins FLRG and follistatin, which may result in an altered effect of activin A on angiogenesis and/or endometrial differentiation. (PMID:17296189)
• TNFalpha activates FLRG expression at the transcriptional level. (PMID:17395406)
• Overexpression of FLRG, an antagonist of activin is associated with increased breast tumor cell growth (PMID:17671190)
• Data show that the nuclear isoform of FLRG lacks an intrinsic transactivation domain, but enhances AF10-mediated transcription, probably through promoting the homo-oligomerization of AF10, thus facilitating the recruitment of co-activators. (PMID:17868029)
• Hypoxia enhances the expression of FSTL3 and its release from PHT cells. (PMID:17959243)
• Elevated myocardial expression of FST-like genes is a feature of heart failure, and may be linked to both disease severity and mechanisms underlying recovery. (PMID:18617621)
• analysis of the structure of the FSTL3.activin A complex (PMID:18768470)
• FLRG expression was regulated in the epithelial cytoplasm and nucleus of the malignant breast tissue. (PMID:19740438)
• First-trimester FSTL3 levels are associated with glucose intolerance and gestational diabetes later in pregnancy. (PMID:20007937)
• FLRG can be successfully detected in maternal plasma in the first trimester of pregnancy but its levels are not significantly altered in the presence of Down syndrome fetuses. (PMID:20063262)
• GDF9 decreases basal and activin A-induced FST and FSTL3 expression, and this explains, in part, its enhancing effects on activin A-induced inhibin beta(B)-subunit mRNA expression and inhibin B production in hGL cells (PMID:21829661)
• Structure of myostatin.follistatin-like 3: N-terminal domains of follistatin-type molecules exhibit alternate modes of binding. (PMID:22052913)
• Maternal and placental FSTL3 concentrations were reduced in GDM women compared with normally pregnant women, suggesting FSTL3 may play an important role in the pathogenesis of gestational diabetes (PMID:22122995)
• After eccentric exercise, postmenopausal women not using hormone therapy (HT) expressed higher levels of follistatin-like protein 3 while postmenopausal women using HT showed a significant increased expression over controls. (PMID:22395277)
• Resistance exercise resulted in a significant downregulation of MSTN and FBXO32 mRNA expression and a significant upregulation in FSTL3 and SMURF1 mRNA expression, and carbohydrate and protein feeding have little influence on the these markers expression. (PMID:22476926)
• Data suggest that serum levels of FSTL3 are higher in pre-eclampsia than in controls; placental expression of FSTL3 is also increased in pre-eclampsia compared with controls; no differences were observed between mild and severe pre-eclampsia. (PMID:22568578)
• Suggest FSTL3 has a role in paracrine communication between cardiomyocytes and fibroblasts. (PMID:22915069)
• The elevation of Follistatin-like-3 was demonstrated in late second trimester of pregnancy destined to developing preeclampsia, suggesting its causal role in the pathogenesis and prediction of preeclampsia. (PMID:24475769)
• Elevated FSTL-3 concentrations were attributable to preeclampsia and were associated with increased likelihood of later developing preeclampsia, suggesting further study as a biomarker prior to clinically evident disease. (PMID:24700053)
• FSTL3 is a critical mediator of exercise-dependent bone formation (PMID:25937185)
• The serum levels of IL-8, MIP-1 alpha, MIP-1 beta, MMP-8, Resistin, FLRG, and BCAM were significantly higher in breast cancer patients, but LAP and TSH-beta levels were lower. (PMID:26898119)
• first trimester maternal serum levels not altered in women who develop gestational diabetes mellitus (PMID:27623975)
• FSTL3 expression in invasive breast cancer is inversely associated with tumor size and nuclear grade but it does not predict disease relapse in the short term. (PMID:28178680)
• Human renal dysfunction is the strongest independent predictor of FSTL3 serum concentrations in multivariate analyses. (PMID:28339962)
• deficient FSTL3 expression by asthmatic Bronchial epithelial cells impairs epithelial regulation of human lung fibroblast and fibroblast-to-myofibroblast transition. (PMID:29394092)
• Aberrant expression of FSTL3 in preeclampsia led to the dysfunction of trophoblast, indicating its involvement in the pathogenesis of preeclampsia. (PMID:30454705)
• FSTL3 plays a biological role in the establishment and maintenance of normal pregnancy. (PMID:31810141)
• Alterations in activin A-myostatin-follistatin system associate with disease activity in inflammatory myopathies. (PMID:31990347)
• [Expression Level of FLRG in Colon Cancer Tissue and Its Clinical Significance]. (PMID:32543143)
• Follistatin-Like 3 Correlates With Lymph Node Metastasis and Serves as a Biomarker of Extracellular Matrix Remodeling in Colorectal Cancer. (PMID:34335633)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fstl3	ENSDARG00000025670
mus_musculus	Fstl3	ENSMUSG00000020325
rattus_norvegicus	Fstl3	ENSRNOG00000009311

Paralogs (6): FSTL4 (ENSG00000053108), SPINK5 (ENSG00000133710), FST (ENSG00000134363), FSTL1 (ENSG00000163430), FSTL5 (ENSG00000168843), SPINK6 (ENSG00000178172)

Protein

Protein identifiers

Follistatin-related protein 3 — O95633 (reviewed: O95633)

Alternative names: Follistatin-like protein 3, Follistatin-related gene protein

All UniProt accessions (4): O95633, A0A087WTD3, A0A087X1Q2, K7EM71

UniProt curated annotations — full annotation on UniProt →

Function. Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such as activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellular signaling; more effective on activin A than on activin B. Involved in bone formation; inhibits osteoclast differentiation. Involved in hematopoiesis; involved in differentiation of hemopoietic progenitor cells, increases hematopoietic cell adhesion to fibronectin and seems to contribute to the adhesion of hematopoietic precursor cells to the bone marrow stroma. Isoform 2 or the nuclear form is probably involved in transcriptional regulation via interaction with MLLT10.

Subunit / interactions. Interacts with INHBA and INHBB. Interacts with FN1. Interacts with ADAM12. Isoform 2 interacts with MLLT10; the interaction enhances MLLT10 in vitro transcriptional activity and self-association. Interacts with MSTN.

Subcellular location. Secreted Nucleus.

Tissue specificity. Expressed in a wide range of tissues.

Disease relevance. A chromosomal aberration involving FSTL3 is found in a case of B-cell chronic lymphocytic leukemia. Translocation t(11;19)(q13;p13) with CCDN1.

Isoforms (2)

UniProt ID	Names	Canonical?
O95633-1	1	yes
O95633-2	2

RefSeq proteins (1): NP_005851* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002350	Kazal_dom	Domain
IPR003645	Fol_N	Domain
IPR015369	Follistatin/Osteonectin_EGF	Domain
IPR017878	TB_dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR036773	TB_dom_sf	Homologous_superfamily
IPR050653	Prot_Inhib_GrowthFact_Antg	Family

Pfam: PF07648, PF09289, PF21333

UniProt features (49 total): strand 19, disulfide bond 13, domain 5, helix 4, glycosylation site 2, signal peptide 1, chain 1, splice variant 1, mutagenesis site 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3SEK	X-RAY DIFFRACTION	2.4
3B4V	X-RAY DIFFRACTION	2.48
2KCX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95633-F1	86.17	0.69

Functional residue map

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

Post-translational modifications (1): 255

Disulfide bonds (13): 38–61, 48–92, 62–95, 99–110, 104–119, 121–153, 125–146, 135–167, 171–182, 176–192, 195–229, 200–222, 211–243

Glycosylation sites (2): 215, 73

Mutagenesis-validated functional residues (1):

Position	Phenotype
27	nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2473224	Antagonism of Activin by Follistatin
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 205 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, TGACCTY_ERR1_Q2, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GTGCCTT_MIR506, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS

GO Biological Process (11): ossification (GO:0001503), hematopoietic progenitor cell differentiation (GO:0002244), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of cell-cell adhesion (GO:0022409), cell differentiation (GO:0030154), regulation of BMP signaling pathway (GO:0030510), negative regulation of BMP signaling pathway (GO:0030514), negative regulation of activin receptor signaling pathway (GO:0032926), negative regulation of osteoclast differentiation (GO:0045671), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090101)

GO Molecular Function (3): fibronectin binding (GO:0001968), activin binding (GO:0048185), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), endoplasmic reticulum lumen (GO:0005788)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by Activin	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
BMP signaling pathway	2
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	2
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	2
cellular anatomical structure	2
multicellular organismal process	1
hemopoiesis	1
cell differentiation	1
regulation of DNA-templated transcription	1
regulation of cell-cell adhesion	1
positive regulation of cell adhesion	1
cell-cell adhesion	1
cellular developmental process	1
regulation of cellular response to growth factor stimulus	1
regulation of BMP signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
activin receptor signaling pathway	1
regulation of activin receptor signaling pathway	1
negative regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cell surface receptor protein serine/threonine kinase signaling pathway	1
negative regulation of signal transduction	1
protein binding	1
protein-containing complex binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
endoplasmic reticulum	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FSTL3	MSTN	O14793	988
FSTL3	GDF11	O95390	864
FSTL3	BMP2	P12643	688
FSTL3	ACVR2A	P27037	682
FSTL3	ANG	P03950	653
FSTL3	INHBA	P08476	638
FSTL3	WFIKKN2	Q8TEU8	624
FSTL3	FSTL1	Q12841	612
FSTL3	ACVR2B	Q13705	601
FSTL3	BMP7	P18075	580
FSTL3	FSTL5	Q8N475	571
FSTL3	BMP6	P22004	570
FSTL3	ADAM12	O43184	553
FSTL3	WFIKKN1	Q96NZ8	525
FSTL3	ACVR1B	P36896	508

IntAct

6 interactions, top by confidence:

A	B	Type	Score
FSTL3	ADAM12	psi-mi:“MI:0915”(physical association)	0.590
ADAM12	FSTL3	psi-mi:“MI:0407”(direct interaction)	0.590
ADAM12	FSTL3	psi-mi:“MI:0915”(physical association)	0.590
FSTL3	ADAM8	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (7): FSTL3 (Affinity Capture-RNA), FSTL3 (Affinity Capture-MS), FSTL3 (Affinity Capture-Western), FSTL3 (Reconstituted Complex), FSTL3 (Proximity Label-MS), FSTL3 (Affinity Capture-RNA), FSTL3 (Proximity Label-MS)

ESM2 similar proteins: A5D8T8, O35217, O75078, O75882, O75900, O88272, O88507, O88676, O95633, P08887, P0C7M8, P0C7M9, P26992, P78539, Q00961, Q01098, Q08406, Q0ZCA7, Q14957, Q1LZB9, Q2TBM7, Q4V7F2, Q5EA46, Q5VV63, Q63769, Q642A6, Q6A051, Q6IA17, Q6P1D5, Q6PCB0, Q6UXF7, Q71DR4, Q7TNS7, Q7TSQ1, Q8NCF0, Q8R2Z5, Q8R366, Q91XD7, Q96FT7, Q96HD1

Diamond homologs: A0A1D5PUP4, A0JP86, A2ASQ1, A3KN33, A5YT95, E9Q7X7, G4V4G1, G5ECE3, O00468, O00634, O09118, O15230, O62650, O75094, O75445, O88280, O94813, O95631, O95633, O95980, P02468, P02469, P07942, P0DKM7, P0DKM8, P0DKM9, P10184, P10669, P11046, P11047, P15215, P15800, P16895, P19883, P21674, P25304, P31514, P31515, P31696, P47931

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FSTL3	down-regulates	MSTN	binding
YAP1	“up-regulates quantity by expression”	FSTL3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

929 predictions. Top by Δscore:

Variant	Effect	Δscore
19:676522:GCCCG:G	donor_gain	1.0000
19:680487:GCA:G	donor_gain	1.0000
19:680490:G:GG	donor_gain	1.0000
19:681316:T:TA	acceptor_gain	1.0000
19:676524:CCGGT:C	donor_loss	0.9900
19:676525:CGGTG:C	donor_loss	0.9900
19:676526:GGTG:G	donor_loss	0.9900
19:676527:G:GG	donor_gain	0.9900
19:676527:G:T	donor_loss	0.9900
19:680456:GACC:G	donor_gain	0.9900
19:680488:CAG:C	donor_loss	0.9900
19:680489:AGTA:A	donor_loss	0.9900
19:680490:GT:G	donor_loss	0.9900
19:680466:TC:T	donor_gain	0.9800
19:680485:CCGCA:C	donor_gain	0.9800
19:680486:CGCA:C	donor_gain	0.9800
19:680487:GCAG:G	donor_gain	0.9800
19:680488:CA:C	donor_gain	0.9800
19:680491:TA:T	donor_loss	0.9800
19:681317:G:A	acceptor_gain	0.9800
19:681320:A:AG	acceptor_gain	0.9800
19:681320:ACCC:A	acceptor_gain	0.9800
19:681328:TGCA:T	acceptor_loss	0.9800
19:681330:CA:C	acceptor_loss	0.9800
19:681331:A:AC	acceptor_loss	0.9800
19:681553:C:G	donor_gain	0.9800
19:681867:GAC:G	donor_gain	0.9800
19:681874:G:GT	donor_gain	0.9800
19:681878:G:GT	donor_gain	0.9800
19:681879:G:T	donor_gain	0.9800

AlphaMissense

1696 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:677805:G:C	W39C	0.998
19:677805:G:T	W39C	0.998
19:677901:G:C	W71C	0.998
19:677901:G:T	W71C	0.998
19:681458:T:A	C211S	0.998
19:681459:G:C	C211S	0.998
19:677869:T:A	C61S	0.997
19:677870:G:C	C61S	0.997
19:680387:T:A	C135S	0.997
19:680388:G:C	C135S	0.997
19:681480:A:G	Y218C	0.997
19:681371:T:A	C182S	0.996
19:681372:G:A	C182Y	0.996
19:681372:G:C	C182S	0.996
19:681479:T:G	Y218D	0.996
19:677902:T:C	S72P	0.995
19:677964:C:G	C92W	0.995
19:677972:G:A	C95Y	0.995
19:680388:G:A	C135Y	0.995
19:680472:A:G	Y163C	0.995
19:681401:T:A	C192S	0.995
19:681402:G:A	C192Y	0.995
19:681402:G:C	C192S	0.995
19:677800:T:A	C38S	0.994
19:677801:G:C	C38S	0.994
19:677871:C:G	C61W	0.994
19:677962:T:A	C92S	0.994
19:677963:G:C	C92S	0.994
19:677971:T:A	C95S	0.994
19:677972:G:C	C95S	0.994

dbSNP variants (sampled 300 via entrez): RS1000126542 (19:683617 G>A), RS1001307917 (19:683846 A>C), RS1001339503 (19:679504 C>T), RS1001340161 (19:678995 G>A), RS1001375366 (19:674412 C>T), RS1001576702 (19:674830 T>C), RS1002508527 (19:681853 C>T), RS1003355452 (19:677117 C>A,T), RS1003592913 (19:676970 G>A), RS1003677929 (19:680745 A>G), RS1003773315 (19:680893 T>A), RS1003815378 (19:680478 G>A,C), RS1003929678 (19:676301 C>A,G,T), RS1004510875 (19:680009 C>A,G,T), RS1004653510 (19:683143 T>C,G)

Disease associations

OMIM: gene MIM:605343 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002928_5	Nickel levels	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression, increases expression	3
Cyclosporine	increases expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
Copper Sulfate	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
diethyl maleate	increases expression	1
beta-lapachone	increases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	decreases expression	1
cupric chloride	increases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
chloropicrin	decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1

Clinical trials (associated diseases)

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