FGF20

Summary

FGF20 (fibroblast growth factor 20, HGNC:3677) is a protein-coding gene on chromosome 8p22, encoding Fibroblast growth factor 20 (Q9NP95). Neurotrophic factor that regulates central nervous development and function.

The protein encoded by this gene is a member of the fibroblast growth factor family. The fibroblast growth factors possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene product is a secreted neurotrophic factor but lacks a typical signal peptide. It is expressed in normal brain, particularly the cerebellum, and may regulate central nervous system development and function. Homodimerization of this protein was shown to regulate its receptor binding activity and concentration gradient in the extracellular matrix. Genetic variations of this gene have been associated with Parkinson disease susceptibility.

Source: NCBI Gene 26281 — RefSeq curated summary.

At a glance

• Gene–disease (curated): renal hypodysplasia/aplasia 2 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 135 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 24
• MANE Select transcript: NM_019851

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3677
Approved symbol	FGF20
Name	fibroblast growth factor 20
Location	8p22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000078579
Ensembl biotype	protein_coding
OMIM	605558
Entrez	26281

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000180166, ENST00000519941

RefSeq mRNA: 1 — MANE Select: NM_019851 NM_019851

CCDS: CCDS5998

Canonical transcript exons

ENST00000180166 — 3 exons

Exon	Start	End
ENSE00001171149	16992181	16993317
ENSE00001320392	17001747	17002345
ENSE00001716619	16995655	16995758

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 94.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3135 / max 223.1430, expressed in 33 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91980	0.2729	17
91981	0.0406	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.02	gold quality
cerebellar cortex	UBERON:0002129	66.57	gold quality
cerebellar hemisphere	UBERON:0002245	66.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	65.38	gold quality
cerebellum	UBERON:0002037	65.18	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.18	gold quality
spinal cord	UBERON:0002240	62.01	gold quality
adrenal tissue	UBERON:0018303	58.21	gold quality
prefrontal cortex	UBERON:0000451	58.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	57.08	gold quality
spleen	UBERON:0002106	56.32	gold quality
right adrenal gland	UBERON:0001233	56.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.96	gold quality
substantia nigra	UBERON:0002038	55.65	gold quality
hypothalamus	UBERON:0001898	55.37	gold quality
right adrenal gland cortex	UBERON:0035827	55.29	gold quality
medial globus pallidus	UBERON:0002477	54.47	gold quality
left adrenal gland cortex	UBERON:0035825	54.33	gold quality
cranial nerve II	UBERON:0000941	54.28	silver quality
left adrenal gland	UBERON:0001234	53.79	gold quality
midbrain	UBERON:0001891	53.76	gold quality
right frontal lobe	UBERON:0002810	53.76	gold quality
adrenal cortex	UBERON:0001235	53.53	gold quality
frontal cortex	UBERON:0001870	53.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	53.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	52.99	gold quality
adrenal gland	UBERON:0002369	52.98	gold quality
anterior cingulate cortex	UBERON:0009835	52.21	gold quality
neocortex	UBERON:0001950	52.18	gold quality
amygdala	UBERON:0001876	52.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, FOXP1, HNF4A, WNT1

miRNA regulators (miRDB)

16 targeting FGF20, 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-340-5P	100.00	72.50	4437
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-4790-3P	96.63	67.08	806
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-8059	95.11	66.30	646
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812
HSA-MIR-4765	93.11	66.17	737

Literature-anchored findings (GeneRIF, showing 30)

• FGF20, FGF9, and FGF16 constitute a subfamily among FGFs. FGF20 is preferentially expressed in colorectal cancer. (PMID:10913340)
• Fibroblast growth factor 20 polymorphisms and haplotypes is associated with the risk of Parkinson disease (PMID:15122513)
• Data show that FGF20 and DKK1 appear to be direct targets for beta-catenin/TCF transcriptional regulation via LEF/TCF-binding sites, and are expressed early in Xenopus embryogenesis under the control of the Wnt signaling pathway (PMID:15592430)
• results suggest that the FGF20 gene is a susceptibility gene for Parkinson’s disease in the Japanese population (PMID:17515805)
• Variants in FGF20 and MAOB show evidence of statistical interactions and potential patterns of biological interaction contributing to Parkinson disease risk. (PMID:18205889)
• Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein. (PMID:18252210)
• FGF20 is associated with Parkinson’s disease synergistically with SNCA. (PMID:18568448)
• Data demonstrate that homodimerization autoregulates FGF9 and FGF20’s receptor binding and concentration gradients in the extracellular matrix. (PMID:19564416)
• The effect of arginine on the solubility and stability of FGF-20 was dominated by the preferential binding interaction. (PMID:19619121)
• The associations described, from mRNA expression to brain morphology to cognition and an interaction with aging, confirm a role of FGF20 in human brain structure and function during development and aging. (PMID:20427658)
• The common FGF20 rs12720208 SNP was not associated with the risk for Parkinson’s disease (PD) in our population. In addition, we did not find nucleotide changes in miR-433 (that binds to the 3’ UTR FGF20 mRNA) among our PD patients. (PMID:20471450)
• This study revealed that the rs1721100(C/G) polymorphism is a risk factor for PD in Han Chinese population, while rs12720208(C/T) polymorphism is not significantly associated with Parkinson’s disease. (PMID:22342445)
• The data suggested that Fgf9/20 and Bmp7 organize the nephron progenitor niche and highlight the essential role of FGF20 in human kidney development. FGF signaling likely regulates multiple important steps in the stem cell niche. (PMID:22698282)
• The results have not shown any effect of rs12720208 in the FGF20 gene on the risk of Parkinson’s disease in patients residing in Russia (PMID:23516905)
• The results showed no significant differences in the presence of rs1721100 or rs12720208 in the FGF20 gene between Parkinson’s disease patients and controls. (PMID:23938014)
• The meta-analysis showed an association between FGF20 gene rs1721100 polymorphism and risk of Parkinson’s disease under a recessive model. (PMID:24942208)
• Meta-analysis suggests that FGF20 rs1721100 C/G polymorphism is associated with sporadic sporadic Parkinson’s diseases in Asians (PMID:25030126)
• The results of this study indicated that rs12720208 may contribute to the risk of PD in Iranian population. (PMID:26070653)
• This study suggested that there is no sufficient evidence to support the association between FGF20 rs12720208 polymorphism and Parkinson’s disease risk. (PMID:27023076)
• the FGF20 gene might not play a dominating role in the genetic predisposition to essential tremor in Chinese Han population. (PMID:27040428)
• Meta-analysis indicated that the rs12720208 polymorphism may be associated with the Parkinson’s disease susceptibility in Caucasians (PMID:28191856)
• This study confirmed that the A allele of rs591323 in FGF20 reduces the risk of developing sporadic PD (P = 0.013). Additionally, subjects with the AA + AG genotype have a reduced risk compared to individuals with the GG genotype (P = 0.024). (PMID:28238162)
• Study observed statistically significant differences in genotypic and allelic frequencies of rs1721100 in the FGF20 gene between Parkinson’s disease cases and controls but not for rs12720208. Results suggest that FGF 20 is a susceptibility gene for Parkinson’s disease in Eastern Indians. (PMID:29604408)
• Studied effect of recombinant human fibroblast growth factor 20 (rhFGF20) on cultured mouse vibrissal follicles; found rhFGF20 significantly induced growth of the follicles in vitro, stimulated proliferation of hair matrix cells, and activated Wnt signal pathway. (PMID:29713847)
• a significant association between a functional polymorphism in the FGF20 gene, which regulates its modulation by miR-433, and depressive symptoms, is reported. (PMID:30241547)
• Fibroblast Growth Factor 20 Gene Polymorphism in Parkinson’s Disease in Asian Population: A Meta-Analysis. (PMID:33947140)
• Association analysis of SYT11, FGF20, GCH1 rare variants in Parkinson’s disease. (PMID:34674384)
• Glioma cell-derived FGF20 suppresses macrophage function by activating beta-catenin. (PMID:34757019)
• FGF20 and PGM2 variants are associated with childhood asthma in family-based whole-genome sequencing studies. (PMID:36255742)
• FGF20. (PMID:38007375)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgf20a	ENSDARG00000007356
danio_rerio	fgf20b	ENSDARG00000086070
mus_musculus	Fgf20	ENSMUSG00000031603
rattus_norvegicus	Fgf20	ENSRNOG00000000109

Paralogs (21): FGF10 (ENSG00000070193), FGF22 (ENSG00000070388), FGF4 (ENSG00000075388), FGF14 (ENSG00000102466), FGF9 (ENSG00000102678), FGF21 (ENSG00000105550), FGF8 (ENSG00000107831), FGF6 (ENSG00000111241), FGF1 (ENSG00000113578), FGF12 (ENSG00000114279), FGF23 (ENSG00000118972), FGF13 (ENSG00000129682), FGF5 (ENSG00000138675), FGF2 (ENSG00000138685), FGF7 (ENSG00000140285), FGF18 (ENSG00000156427), FGF17 (ENSG00000158815), FGF11 (ENSG00000161958), FGF19 (ENSG00000162344), FGF3 (ENSG00000186895), FGF16 (ENSG00000196468)

Protein

Protein identifiers

Fibroblast growth factor 20 — Q9NP95 (reviewed: Q9NP95)

All UniProt accessions (3): Q9NP95, A0A7U3L649, H0YAT9

UniProt curated annotations — full annotation on UniProt →

Function. Neurotrophic factor that regulates central nervous development and function.

Subunit / interactions. Homodimer. Interacts with FGFR2 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.

Subcellular location. Secreted.

Tissue specificity. Predominantly expressed in the cerebellum.

Disease relevance. Renal hypodysplasia/aplasia 2 (RHDA2) [MIM:615721] A perinatally lethal renal disease encompassing a spectrum of kidney development defects, including renal agenesis, bilateral renal aplasia, hypoplasia, (cystic) dysplasia, and severe obstructive uropathy. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the heparin-binding growth factors family.

RefSeq proteins (1): NP_062825* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002209	Fibroblast_GF_fam	Family
IPR008996	IL1/FGF	Homologous_superfamily

Pfam: PF00167

UniProt features (27 total): strand 12, helix 6, turn 3, sequence variant 3, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3F1R	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP95-F1	83.52	0.65

Function

Pathways and Gene Ontology

Reactome pathways

37 pathways

ID	Pathway
R-HSA-109704	PI3K Cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1839122	Signaling by activated point mutants of FGFR1
R-HSA-1839130	Signaling by activated point mutants of FGFR3
R-HSA-190322	FGFR4 ligand binding and activation
R-HSA-190371	FGFR3b ligand binding and activation
R-HSA-190372	FGFR3c ligand binding and activation
R-HSA-190373	FGFR1c ligand binding and activation
R-HSA-190375	FGFR2c ligand binding and activation
R-HSA-2033519	Activated point mutants of FGFR2
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5654219	Phospholipase C-mediated cascade: FGFR1
R-HSA-5654221	Phospholipase C-mediated cascade; FGFR2
R-HSA-5654227	Phospholipase C-mediated cascade; FGFR3
R-HSA-5654228	Phospholipase C-mediated cascade; FGFR4
R-HSA-5654687	Downstream signaling of activated FGFR1
R-HSA-5654688	SHC-mediated cascade:FGFR1
R-HSA-5654689	PI-3K cascade:FGFR1
R-HSA-5654693	FRS-mediated FGFR1 signaling
R-HSA-5654695	PI-3K cascade:FGFR2
R-HSA-5654699	SHC-mediated cascade:FGFR2
R-HSA-5654700	FRS-mediated FGFR2 signaling
R-HSA-5654704	SHC-mediated cascade:FGFR3
R-HSA-5654706	FRS-mediated FGFR3 signaling
R-HSA-5654710	PI-3K cascade:FGFR3
R-HSA-5654712	FRS-mediated FGFR4 signaling
R-HSA-5654719	SHC-mediated cascade:FGFR4
R-HSA-5654720	PI-3K cascade:FGFR4
R-HSA-5654726	Negative regulation of FGFR1 signaling
R-HSA-5654727	Negative regulation of FGFR2 signaling

MSigDB gene sets: 279 (showing top): REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, FREAC2_01, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, KEGG_MAPK_SIGNALING_PATHWAY, REACTOME_FGFR2C_LIGAND_BINDING_AND_ACTIVATION, REACTOME_SIGNALING_BY_FGFR, REACTOME_FGFR1_LIGAND_BINDING_AND_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEUROGENESIS, GOMF_GROWTH_FACTOR_ACTIVITY

GO Biological Process (15): signal transduction (GO:0007165), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), fibroblast growth factor receptor signaling pathway (GO:0008543), regulation of dopamine secretion (GO:0014059), neurogenesis (GO:0022008), regulation of cell migration (GO:0030334), inner ear auditory receptor cell differentiation (GO:0042491), positive regulation of MAPK cascade (GO:0043410), negative regulation of neuron apoptotic process (GO:0043524), regulation of cardiac muscle cell proliferation (GO:0060043), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of dopaminergic neuron differentiation (GO:1904340), cell differentiation (GO:0030154), regulation of neuron differentiation (GO:0045664)

GO Molecular Function (5): signaling receptor binding (GO:0005102), fibroblast growth factor receptor binding (GO:0005104), growth factor activity (GO:0008083), heparan sulfate proteoglycan binding (GO:0043395), receptor-receptor interaction (GO:0090722)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Downstream signaling of activated FGFR1	4
FGFR3 ligand binding and activation	2
Downstream signaling of activated FGFR2	2
IRS-mediated signalling	1
Intracellular signaling by second messengers	1
FGFR1 mutant receptor activation	1
FGFR3 mutant receptor activation	1
Signaling by FGFR4	1
FGFR1 ligand binding and activation	1
FGFR2 ligand binding and activation	1
FGFR2 mutant receptor activation	1
PI3K/AKT Signaling in Cancer	1
Downstream signaling of activated FGFR3	1
Downstream signaling of activated FGFR4	1
Signaling by FGFR1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
regulation of cell population proliferation	2
cellular anatomical structure	2
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
dopamine secretion	1
regulation of catecholamine secretion	1
nervous system development	1
cell differentiation	1
cell migration	1
regulation of cell motility	1
hair cell differentiation	1
inner ear receptor cell differentiation	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
regulation of cardiac muscle tissue growth	1
cardiac muscle cell proliferation	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
positive regulation of neuron differentiation	1
dopaminergic neuron differentiation	1
regulation of dopaminergic neuron differentiation	1
cellular developmental process	1
neuron differentiation	1
regulation of cell differentiation	1
protein binding	1
growth factor receptor binding	1
receptor ligand activity	1
proteoglycan binding	1

Protein interactions and networks

STRING

3791 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGF20	FGFR1	P11362	995
FGF20	EGF	P01133	988
FGF20	KL	Q9UEF7	987
FGF20	FGFR4	P22455	972
FGF20	FGFR2	P18443	967
FGF20	HSPG2	P98160	948
FGF20	FGFBP1	Q14512	945
FGF20	DCN	P07585	937
FGF20	CD44	P16070	887
FGF20	CDH2	P19022	881
FGF20	FGFR3	P22607	877
FGF20	HGF	P14210	868
FGF20	KLB	Q86Z14	848
FGF20	FRS2	Q8WU20	838
FGF20	SHH	Q15465	830

IntAct

4 interactions, top by confidence:

A	B	Type	Score
FGF9	PPID	psi-mi:“MI:0914”(association)	0.530
	FGF20	psi-mi:“MI:0407”(direct interaction)	0.440
FGF9	GTF2F1	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): FGF20 (Affinity Capture-MS), PTX3 (Reconstituted Complex), FGF20 (Affinity Capture-MS)

ESM2 similar proteins: A0MTF4, A4Q9F4, M3X9S6, O15520, O35565, O43189, O43320, O54693, O54769, O73754, O95750, P05524, P08620, P11487, P12034, P15656, P31371, P36364, P36386, P48801, P48802, P48803, P48804, P48807, P54130, P70492, P97401, P98172, Q20FD0, Q2HXK8, Q3ZFI5, Q5RF67, Q5T6S3, Q5XI70, Q91875, Q92765, Q92838, Q95117, Q95L12, Q96GD3

Diamond homologs: A0MTF4, A6P7H6, M3X9S6, O15520, O35565, O43320, O54769, P03968, P03969, P05230, P05524, P08620, P09038, P10767, P11403, P11487, P12034, P12226, P13109, P15655, P15656, P19596, P20002, P20003, P21658, P21781, P31371, P34004, P36363, P36364, P36386, P48798, P48799, P48800, P48801, P48802, P48803, P48804, P48805, P48806

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	86
Likely benign	28
Benign	17

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
126502	NM_019851.3(FGF20):c.337del (p.Val113fs)	Pathogenic
802391	NM_019851.3(FGF20):c.391-1G>A	Likely pathogenic

SpliceAI

295 predictions. Top by Δscore:

Variant	Effect	Δscore
8:16993313:TTCTC:T	acceptor_gain	1.0000
8:16993315:CTC:C	acceptor_gain	1.0000
8:16993316:TCCTG:T	acceptor_loss	1.0000
8:16993317:CCTGA:C	acceptor_loss	1.0000
8:16993318:C:CC	acceptor_gain	1.0000
8:16993318:CTG:C	acceptor_loss	1.0000
8:16995650:CGT:C	donor_loss	1.0000
8:16995651:GTA:G	donor_loss	1.0000
8:16995652:TACTG:T	donor_loss	1.0000
8:16995653:A:AC	donor_gain	1.0000
8:16995653:A:T	donor_loss	1.0000
8:16995654:C:CG	donor_gain	1.0000
8:16995654:CTG:C	donor_gain	1.0000
8:16995654:CTGAT:C	donor_gain	1.0000
8:17001743:GTA:G	donor_loss	1.0000
8:17001744:TA:T	donor_loss	1.0000
8:17001745:A:AC	donor_gain	1.0000
8:17001746:C:CG	donor_gain	1.0000
8:17001746:CCG:C	donor_gain	1.0000
8:17001746:CCGA:C	donor_gain	1.0000
8:16993316:TC:T	acceptor_gain	0.9900
8:16993317:CC:C	acceptor_gain	0.9900
8:16995646:AATAC:A	donor_loss	0.9900
8:16995647:ATACG:A	donor_loss	0.9900
8:16995648:TACGT:T	donor_loss	0.9900
8:16995649:ACGTA:A	donor_loss	0.9900
8:16995650:CGTA:C	donor_gain	0.9900
8:16995654:CT:C	donor_gain	0.9900
8:16995654:CTGA:C	donor_gain	0.9900
8:16995755:ATACC:A	acceptor_loss	0.9900

AlphaMissense

1359 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:16993136:A:G	L191S	1.000
8:16993138:G:C	F190L	1.000
8:16993138:G:T	F190L	1.000
8:16993139:A:C	F190C	1.000
8:16993139:A:G	F190S	1.000
8:16993140:A:G	F190L	1.000
8:16993143:G:C	H189D	1.000
8:16993175:C:T	G178D	1.000
8:16993190:C:A	G173V	1.000
8:16993190:C:T	G173E	1.000
8:16993202:A:G	L169P	1.000
8:16993202:A:T	L169H	1.000
8:16993250:G:A	S153F	1.000
8:16993254:A:G	S152P	1.000
8:16993257:A:C	Y151D	1.000
8:16993257:A:G	Y151H	1.000
8:16993261:G:C	N149K	1.000
8:16993261:G:T	N149K	1.000
8:16993270:G:C	N146K	1.000
8:16993270:G:T	N146K	1.000
8:16993285:C:A	E141D	1.000
8:16993285:C:G	E141D	1.000
8:16993292:A:C	F139C	1.000
8:16993292:A:G	F139S	1.000
8:16995659:C:T	G129E	1.000
8:16995671:C:A	G125V	1.000
8:16995671:C:T	G125E	1.000
8:16995689:A:G	L119P	1.000
8:16995689:A:T	L119H	1.000
8:16995716:A:T	I110N	1.000

dbSNP variants (sampled 300 via entrez): RS1000001925 (8:16992044 T>A,C), RS1000084734 (8:16999264 A>G), RS1000193361 (8:16992825 G>A), RS1000399884 (8:16992602 A>C,T), RS1000463229 (8:16991849 A>C,T), RS1000581619 (8:17001699 G>A,T), RS1000757925 (8:16997210 C>A), RS1000938838 (8:17000928 C>T), RS1001180548 (8:16991795 C>G), RS1001391124 (8:17000696 C>G,T), RS1001460232 (8:16992525 A>C), RS1001524187 (8:16996982 A>C), RS1001743663 (8:17001000 G>A,T), RS1001973439 (8:16992276 G>C), RS1002091251 (8:17001219 C>T)

Disease associations

OMIM: gene MIM:605558 | disease phenotypes: MIM:615721, MIM:168600

GenCC curated gene-disease

Disease	Classification	Inheritance
renal hypodysplasia/aplasia 2	Moderate	Autosomal recessive
bilateral renal agenesis	Supportive	Autosomal recessive

Mondo (3): renal hypodysplasia/aplasia 2 (MONDO:0014319), late-onset Parkinson disease (MONDO:0008199), bilateral renal agenesis (MONDO:0015986)

Orphanet (2): Renal agenesis (Orphanet:411709), Hereditary late-onset Parkinson disease (Orphanet:411602)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000104	Renal agenesis
HP:0000175	Cleft palate
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000369	Low-set ears
HP:0000457	Depressed nasal ridge
HP:0001562	Oligohydramnios
HP:0001563	Fetal polyuria
HP:0001582	Redundant skin
HP:0001958	Nonketotic hypoglycemia
HP:0002009	Potter facies
HP:0002089	Pulmonary hypoplasia
HP:0002242	Abnormal intestine morphology
HP:0002575	Tracheoesophageal fistula
HP:0005107	Abnormal sacrum morphology
HP:0010497	Sirenomelia
HP:0010958	Bilateral renal agenesis
HP:0025700	Anhydramnios
HP:0030674	Antenatal onset
HP:0030680	Abnormal cardiovascular system morphology
HP:0100335	Non-midline cleft of the upper lip
HP:0100589	Urogenital fistula

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002544_9	Parkinson’s disease	7.000000e-08
GCST002552_1	Allergic rhinitis in asthma	3.000000e-07
GCST003025_4	Attention function in attention deficit hyperactive disorder	4.000000e-06
GCST007325_184	General risk tolerance (MTAG)	1.000000e-08
GCST009325_46	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	3.000000e-15
GCST011743_46	HDL cholesterol levels in HIV infection	1.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007636	attention function measurement
EFO:0008579	risk-taking behaviour
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
manganese chloride	increases expression	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	affects cotreatment, increases expression	1
abrine	increases expression	1
bisphenol S	increases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Dinoprostone	increases abundance	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00455143	PHASE4	TERMINATED	Cognitive Protection - Dexmedetomidine and Cognitive Reserve
NCT00561678	PHASE4	COMPLETED	Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
NCT01807481	PHASE4	UNKNOWN	Phase IV Study to Evaluate the Efficacy and Safety of Mircera in PD
NCT07015671	PHASE3	COMPLETED	Bioavailability and Bioequivalence Study of ER Torsemide and Spironolactone FDC Tablet in Healthy Subjects
NCT03942458	PHASE1	COMPLETED	Pharmacokinetics and Pharmacodynamics of Vicagrel in Healthy Adult Subjects of Different CYP2C19
NCT07195825	PHASE1	RECRUITING	A Clinical Study to Evaluate the Safety, and Tolerability of BBM-P002 in the Treatment of Parkinson’s Disease
NCT06728228	Not specified	RECRUITING	Amnioinfusion for Fetal Renal Failure
NCT04093349	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Gene Transfer Study for Late-Onset Pompe Disease (RESOLUTE)
NCT07282847	PHASE1/PHASE2	RECRUITING	A Study to Evaluate Safety, Tolerability, and Efficacy of AB-1009 Gene Therapy (GAA Gene) in Adult Participants With Late Onset Pompe Disease (PROGRESS-GT LOPD)
NCT00105131	Not specified	COMPLETED	Genetic Characterization of Parkinson’s Disease
NCT03021408	Not specified	UNKNOWN	Effectiveness of Different Approaches for the Rehabilitation of Gait in Patients With Parkinson’s Disease
NCT03893240	Not specified	COMPLETED	Neutralizing Antibody Seroprevalence Study With a Retrospective Component in Participants With Late-Onset Pompe Disease
NCT05810454	Not specified	NOT_YET_RECRUITING	iPACES v3 MCI NIA Protocol Copied for iPACES v4 PD NINDS