FBP2

Summary

FBP2 (fructose-bisphosphatase 2, HGNC:3607) is a protein-coding gene on chromosome 9q22.32, encoding Fructose-1,6-bisphosphatase isozyme 2 (O00757). Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations and probably participates in glycogen synthesis from carbohydrate precursors, such as lactate.

This gene encodes a gluconeogenesis regulatory enzyme which catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate.

Source: NCBI Gene 8789 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukodystrophy, childhood-onset, remitting (Moderate, GenCC)
• Clinical variants (ClinVar): 69 total — 1 pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_003837

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3607
Approved symbol	FBP2
Name	fructose-bisphosphatase 2
Location	9q22.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000130957
Ensembl biotype	protein_coding
OMIM	603027
Entrez	8789

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000375337

RefSeq mRNA: 1 — MANE Select: NM_003837 NM_003837

CCDS: CCDS6711

Canonical transcript exons

ENST00000375337 — 7 exons

Exon	Start	End
ENSE00000895731	94571462	94571602
ENSE00000895733	94587307	94587469
ENSE00001466735	94558720	94559132
ENSE00001466739	94593557	94593824
ENSE00001672838	94567270	94567407
ENSE00001700786	94563342	94563461
ENSE00001794191	94584577	94584669

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 98.43.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6803 / max 233.6945, expressed in 46 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101512	0.4726	39
101511	0.1232	25
101513	0.0845	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	98.43	gold quality
biceps brachii	UBERON:0001507	98.24	gold quality
vastus lateralis	UBERON:0001379	97.93	gold quality
triceps brachii	UBERON:0001509	97.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.65	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.48	gold quality
quadriceps femoris	UBERON:0001377	97.03	gold quality
gastrocnemius	UBERON:0001388	96.08	gold quality
skeletal muscle tissue	UBERON:0001134	95.56	gold quality
muscle organ	UBERON:0001630	94.74	gold quality
gluteal muscle	UBERON:0002000	94.11	gold quality
muscle of leg	UBERON:0001383	93.98	gold quality
diaphragm	UBERON:0001103	93.50	gold quality
body of tongue	UBERON:0011876	89.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.25	gold quality
muscle tissue	UBERON:0002385	88.81	gold quality
deltoid	UBERON:0001476	88.53	gold quality
choroid plexus epithelium	UBERON:0003911	87.29	gold quality
body of stomach	UBERON:0001161	81.09	gold quality
secondary oocyte	CL:0000655	80.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.64	gold quality
stomach	UBERON:0000945	78.60	gold quality
tongue	UBERON:0001723	75.21	gold quality
oocyte	CL:0000023	70.58	gold quality
endometrium epithelium	UBERON:0004811	69.28	gold quality
fundus of stomach	UBERON:0001160	69.26	gold quality
pigmented layer of retina	UBERON:0001782	68.78	silver quality
body of pancreas	UBERON:0001150	68.72	gold quality
tibialis anterior	UBERON:0001385	67.86	silver quality
olfactory bulb	UBERON:0002264	67.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting FBP2, 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-3692-3P	99.98	70.27	2139
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-554	95.20	66.98	341

Literature-anchored findings (GeneRIF, showing 8)

• The key role in strong AMP binding to muscle isozyme play K20, T177 and Q179. (PMID:16213487)
• The existence of highly AMP-sensitive muscle-like FBPase, activity of which is regulated by metabolite-dependent interaction with aldolase enables the precise regulation of muscle energy expenditures. (PMID:18214967)
• FBP2 does negatively regulate cell growth, and reduced expression of FBP2 may contribute to carcinogenesis for gastric cancer. (PMID:24063558)
• Results demonstrate that truncation of the evolutionarily conserved N-terminal residues of FBP2 results in a loss of its mitochondria-protective functions. (PMID:24412565)
• Fructose-1,6-Bisphosphatase 2 Inhibits Sarcoma Progression by Restraining Mitochondrial Biogenesis. (PMID:31761563)
• The Reverse Warburg Effect is Associated with Fbp2-Dependent Hif1alpha Regulation in Cancer Cells Stimulated by Fibroblasts. (PMID:31947613)
• TRIM32 promotes oral squamous cell carcinoma progression by enhancing FBP2 ubiquitination and degradation. (PMID:37640002)
• DNA methyltransferase 3a-induced hypermethylation of the fructose-1,6-bisphosphatase-2 promoter contributes to gastric carcinogenesis. (PMID:38183507)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbp2	ENSDARG00000012366
mus_musculus	Fbp2	ENSMUSG00000021456
rattus_norvegicus	Fbp2	ENSRNOG00000017637
drosophila_melanogaster	fbp	FBGN0032820
caenorhabditis_elegans	fbp-1	WBGENE00001404

Paralogs (1): FBP1 (ENSG00000165140)

Protein

Protein identifiers

Fructose-1,6-bisphosphatase isozyme 2 — O00757 (reviewed: O00757)

Alternative names: D-fructose-1,6-bisphosphate 1-phosphohydrolase 2, Muscle FBPase

All UniProt accessions (1): O00757

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations and probably participates in glycogen synthesis from carbohydrate precursors, such as lactate.

Subunit / interactions. Homotetramer. Interacts with ALDOA; the interaction blocks inhibition by physiological concentrations of AMP and reduces inhibition by Ca(2+). Interacts with alpha-actinin and F-actin.

Subcellular location. Cell junction. Cytoplasm. Nucleus. Myofibril. Sarcomere. Z line.

Tissue specificity. Expressed in skeletal muscle (at protein level).

Disease relevance. Leukodystrophy, childhood-onset, remitting (CORLK) [MIM:619864] An autosomal dominant disorder characterized by loss of developmental abilities, demyelination and leukodystrophy on brain imaging, triggered by fever or infection in the first year of life. Abnormalities almost completely resolve over a period of 1 to 2 years, and affected children regain normal development accompanied by remyelination. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as an allosteric inhibitor. Fructose 2,6-bisphosphate acts as a competitive inhibitor. Strongly inhibited by Ca(2+).

Cofactor. Binds 3 Mg(2+) ions per subunit.

Pathway. Carbohydrate biosynthesis; gluconeogenesis.

Miscellaneous. Specific for the alpha-anomer of the substrate. The Arg-33 mutant form has been shown to act on the beta-anomer.

Similarity. Belongs to the FBPase class 1 family.

RefSeq proteins (1): NP_003828* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000146	FBPase_class-1	Family
IPR020548	Fructose_bisphosphatase_AS	Active_site
IPR028343	FBPtase	Family
IPR033391	FBPase_N	Domain
IPR044015	FBPase_C_dom	Domain

Pfam: PF00316, PF18913

Enzyme classification (BRENDA):

• EC 3.1.3.11 — fructose-bisphosphatase (BRENDA: 105 organisms, 146 substrates, 726 inhibitors, 228 Km, 143 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-FRUCTOSE 1,6-BISPHOSPHATE	0.0001–3.2	136
FRUCTOSE 1,6-DIPHOSPHATE	0.0005–0.057	51
SEDOHEPTULOSE 1,7-DIPHOSPHATE	0.0026–1.4	8
BETA-D-GLUCOSE 1,6-BISPHOSPHATE	0.0026–0.17	7
D-FRUCTOSE-1,6-BISPHOSPHATE	0.0018–0.035	3
D-FRUCTOSE 1,6-DIPHOSPHATE	0.0111–99.98	2
FRUCTOSE 1,6-BISPHOSPHATE	0.1–0.45	2
RIBULOSE 1,5-DIPHOSPHATE	0.0031–0.021	2
D-FRUCTOSE 1-PHOSPHATE	1	1
SEDOHEPTULOSE 1,6-DIPHOSPHATE	0.016	1
SEDOHEPTULOSE-1,7-DIPHOSPHATE	0.118	1

Catalyzed reactions (Rhea), 1 shown:

• beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6-phosphate + phosphate (RHEA:11064)

UniProt features (78 total): mutagenesis site 18, binding site 17, strand 16, helix 13, turn 6, modified residue 2, sequence variant 2, chain 1, region of interest 1, short sequence motif 1, site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
4HE2	X-RAY DIFFRACTION	1.6
5ET5	X-RAY DIFFRACTION	1.67
5K54	X-RAY DIFFRACTION	1.72
5ET6	X-RAY DIFFRACTION	1.84
5ET8	X-RAY DIFFRACTION	1.92
3IFA	X-RAY DIFFRACTION	1.93
3IFC	X-RAY DIFFRACTION	1.97
5K55	X-RAY DIFFRACTION	1.98
5K56	X-RAY DIFFRACTION	2.2
4HE1	X-RAY DIFFRACTION	2.23
5L0A	X-RAY DIFFRACTION	2.3
5Q0C	X-RAY DIFFRACTION	2.4
4HE0	X-RAY DIFFRACTION	2.69
5ET7	X-RAY DIFFRACTION	2.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00757-F1	93.87	0.86

Functional residue map

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

Catalytic / active sites (1): 33 (important for the conversion from active r-state to inactive t-state in the presence of amp)

Ligand- & substrate-binding residues (17): 119; 121; 122; 122; 141; 213–216; 245–249; 265; 275; 281; 18; 28–32 …

Post-translational modifications (2): 216, 219

Mutagenesis-validated functional residues (18):

Position	Phenotype
1–10	greatly reduces sensitivity to inhibition by amp and ca(2+) and activation by mg(2+). decreases binding to aldoa.
1–7	greatly reduces sensitivity to inhibition by amp and ca(2+) and activation by mg(2+). decreases binding to aldoa.
1–6	reduces sensitivity to inhibition by amp and ca(2+) and activation by mg(2+). decreases binding to aldoa.
1–5	reduces sensitivity to inhibition by amp and ca(2+) and activation by mg(2+). decreases binding to aldoa.
1–4	slightly reduces sensitivity to inhibition by amp and ca(2+) and activation by mg(2+). decreases binding to aldoa.
1–3	no effect on kinetic properties but decreases binding to aldoa.
1–2	no effect on kinetic properties and interaction with aldoa.
1	no effect on kinetic properties and interaction with aldoa.
21	reduces sensitivity to amp; when associated with m-178 and c-180.
33	causes conformational change of n-terminal residues and decreased sensitivity towards amp with lack of conversion to the
70	greatly reduces affinity towards ca(2+) and slightly reduces affinity towards mg(2+).
178	reduces sensitivity to amp; when associated with e-21 and c-180.
180	reduces sensitivity to amp; when associated with e-21 and m-178.
204–208	almost completely abolishes nuclear localization.
204	minor reduction in nuclear localization.
205	minor reduction in nuclear localization.
206	greatly reduces nuclear lozalization.
208	significantly reduces nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70263	Gluconeogenesis

MSigDB gene sets: 97 (showing top): KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MARTINEZ_RB1_TARGETS_UP, MODULE_205, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS, MOOTHA_GLUCONEOGENESIS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, REACTOME_GLUCONEOGENESIS, TGANTCA_AP1_C, KEGG_PENTOSE_PHOSPHATE_PATHWAY, GOBP_GLUCOSE_METABOLIC_PROCESS, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, JECHLINGER_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, PPARA_01, chr9q22

GO Biological Process (5): fructose metabolic process (GO:0006000), fructose 6-phosphate metabolic process (GO:0006002), gluconeogenesis (GO:0006094), fructose 1,6-bisphosphate metabolic process (GO:0030388), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (8): fructose 1,6-bisphosphate 1-phosphatase activity (GO:0042132), identical protein binding (GO:0042802), metal ion binding (GO:0046872), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791), phosphoric ester hydrolase activity (GO:0042578)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), Z disc (GO:0030018), extracellular exosome (GO:0070062), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glucose metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
organophosphate metabolic process	2
carbohydrate derivative metabolic process	2
hexose metabolic process	1
glucose metabolic process	1
hexose biosynthetic process	1
primary metabolic process	1
sugar-phosphatase activity	1
protein binding	1
cation binding	1
molecular_function	1
binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
hydrolase activity, acting on ester bonds	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
I band	1
extracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1916 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBP2	ZBTB22	O15209	952
FBP2	PFKFB2	O60825	708
FBP2	PFKM	P08237	702
FBP2	PFKFB3	Q16875	694
FBP2	PFKFB1	P16118	634
FBP2	GPI	P06744	625
FBP2	PFKL	P17858	609
FBP2	PFKP	Q01813	608
FBP2	PKLR	P11973	604
FBP2	PFKFB4	Q16877	602
FBP2	PC	P11498	591
FBP2	RPEL1	Q2QD12	591
FBP2	TIGAR	Q9NQ88	581
FBP2	G6PC2	Q9NQR9	570
FBP2	TPI1	P00938	569

IntAct

58 interactions, top by confidence:

A	B	Type	Score
FBP1	FBP2	psi-mi:“MI:0915”(physical association)	0.920
FBP2	FBP1	psi-mi:“MI:0915”(physical association)	0.920
FBP2	FBP2	psi-mi:“MI:0915”(physical association)	0.740
HSPB1	FBP2	psi-mi:“MI:0915”(physical association)	0.560
PRKN	FBP2	psi-mi:“MI:0915”(physical association)	0.560
FBP2	PRPS1	psi-mi:“MI:0915”(physical association)	0.560
KIF1B	FBP2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (37): FBP2 (Two-hybrid), FBP2 (Two-hybrid), FBP1 (Affinity Capture-MS), FBP2 (Two-hybrid), FBP1 (Affinity Capture-MS), CHD3 (Two-hybrid), FBP2 (Two-hybrid), FBP1 (Two-hybrid), FBP2 (Two-hybrid), FBP2 (Two-hybrid), FBP2 (Two-hybrid), FBP2 (Two-hybrid), FBP2 (Two-hybrid), FBP2 (Two-hybrid), FBP2 (Two-hybrid)

ESM2 similar proteins: A1AJD7, A2WXB2, A6THE3, A7MM48, A7ZVB0, A8A7Y7, A8AMG4, A9N548, B1ISX3, B1LRB5, B1XEL4, B2TZ12, B4T3H9, B5BKN5, B5FSC7, B5R0U4, B5Y2X3, B5Z3I7, O00757, P00636, P00637, P09199, P09467, P0A993, P0A994, P0A995, P14766, P46267, P46276, Q0JHF8, Q0SXH4, Q0T9F7, Q1R324, Q2KJJ9, Q31TG8, Q328V4, Q3SZB7, Q42649, Q43139, Q57GG7

Diamond homologs: A0RP36, A1APW8, A1B2P8, A1VZI4, A2RQ29, A2ST39, A2WXB2, A3QAZ7, A4XPL2, A5EVS5, A5G439, A6Q349, A6Q9C9, A6SVE7, A6VDM7, A7GXH6, A7H3L9, A7I1B8, A7I8R6, A7ZCB2, A8EU55, A8FLP9, B0C7G7, B0JH56, B0R3Y1, B1WX40, B2T699, B2U8C4, B2UVU9, B2V6E2, B3E2M3, B3R3R6, B4S2E8, B5EFV5, B5Z9G5, B7V3K3, C0QTP7, C1DHU3, O00757, O20252

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FBP2	“down-regulates quantity”	“beta-D-fructofuranose 1,6-bisphosphate(4-)”	“chemical modification”
FBP2	“up-regulates quantity”	“β-D-fructose 6-phosphate”	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of gene expression	6	14.8×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	56
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
685192	GRCh37/hg19 9p24.3-q34.3(chr9:203861-141020388)x3	Pathogenic

SpliceAI

846 predictions. Top by Δscore:

Variant	Effect	Δscore
9:94559128:CGGAG:C	acceptor_gain	1.0000
9:94559131:AGC:A	acceptor_loss	1.0000
9:94559132:GCT:G	acceptor_loss	1.0000
9:94559133:C:CC	acceptor_gain	1.0000
9:94559133:CT:C	acceptor_loss	1.0000
9:94559134:T:G	acceptor_loss	1.0000
9:94571456:ACCT:A	donor_loss	1.0000
9:94571458:CTA:C	donor_loss	1.0000
9:94571459:TA:T	donor_loss	1.0000
9:94571460:A:T	donor_loss	1.0000
9:94571461:C:CT	donor_loss	1.0000
9:94571603:C:CC	acceptor_gain	1.0000
9:94584572:CTCA:C	donor_loss	1.0000
9:94584573:TCAC:T	donor_loss	1.0000
9:94584574:CACCT:C	donor_loss	1.0000
9:94584575:A:AC	donor_gain	1.0000
9:94584575:A:AT	donor_loss	1.0000
9:94584575:AC:A	donor_gain	1.0000
9:94584576:C:CC	donor_gain	1.0000
9:94584576:C:CT	donor_loss	1.0000
9:94584576:CC:C	donor_gain	1.0000
9:94584576:CCT:C	donor_gain	1.0000
9:94584576:CCTTT:C	donor_gain	1.0000
9:94584666:TCCC:T	acceptor_gain	1.0000
9:94584667:CCCC:C	acceptor_gain	1.0000
9:94584669:CCTAA:C	acceptor_loss	1.0000
9:94584670:C:CC	acceptor_gain	1.0000
9:94584671:T:G	acceptor_loss	1.0000
9:94584676:C:CT	acceptor_gain	1.0000
9:94587249:A:AC	donor_gain	1.0000

AlphaMissense

2183 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:94563403:C:G	R255P	0.999
9:94563436:C:A	R244M	0.999
9:94567342:G:C	S211R	0.999
9:94567342:G:T	S211R	0.999
9:94567344:T:G	S211R	0.999
9:94571542:C:G	A163P	0.999
9:94584625:A:C	N126K	0.999
9:94584625:A:T	N126K	0.999
9:94584635:C:T	G123E	0.999
9:94584636:C:G	G123R	0.999
9:94584636:C:T	G123R	0.999
9:94563378:G:C	F263L	0.998
9:94563378:G:T	F263L	0.998
9:94563380:A:G	F263L	0.998
9:94563385:C:A	G261V	0.998
9:94563385:C:T	G261E	0.998
9:94563388:C:A	G260V	0.998
9:94563404:G:T	R255S	0.998
9:94563413:C:G	D252H	0.998
9:94563435:C:A	R244S	0.998
9:94563435:C:G	R244S	0.998
9:94563436:C:G	R244T	0.998
9:94567336:A:C	N213K	0.998
9:94567336:A:T	N213K	0.998
9:94571519:A:C	S170R	0.998
9:94571519:A:T	S170R	0.998
9:94571521:T:G	S170R	0.998
9:94571538:C:T	G164D	0.998
9:94584602:C:T	G134E	0.998
9:94584635:C:A	G123V	0.998

dbSNP variants (sampled 300 via entrez): RS1000039798 (9:94586955 G>A), RS1000112151 (9:94559322 A>C), RS1000204080 (9:94567204 A>G), RS1000265667 (9:94563396 C>G), RS1000340330 (9:94563696 A>G), RS1000358440 (9:94564190 TCA>T), RS1000438182 (9:94591560 C>T), RS1000606578 (9:94569125 A>C,G), RS1000661324 (9:94574303 T>C), RS1000691407 (9:94562904 A>C,G), RS1000810988 (9:94568462 A>C), RS1000867531 (9:94574285 T>G), RS1000957324 (9:94573874 T>C), RS1000991144 (9:94592040 A>C), RS1001023782 (9:94581424 G>C)

Disease associations

OMIM: gene MIM:603027 | disease phenotypes: MIM:619864

GenCC curated gene-disease

Disease	Classification	Inheritance
leukodystrophy, childhood-onset, remitting	Moderate	Autosomal dominant

Mondo (2): leukodystrophy, childhood-onset, remitting (MONDO:0859246), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000737	Irritability
HP:0001288	Gait disturbance
HP:0002415	Leukodystrophy
HP:0002500	Abnormal cerebral white matter morphology
HP:0003593	Infantile onset
HP:0007359	Focal-onset seizure
HP:0011968	Feeding difficulties
HP:0033454	Tube feeding

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects expression, affects methylation	1
arsenite	increases methylation	1
benzo(e)pyrene	decreases methylation	1
15-acetyldeoxynivalenol	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
N,N’-((5-(2-amino-5-(2-methylpropyl)-4-thiazolyl)-2-furanyl)phosphinylidene)bis(alanine) diethyl ester	decreases activity	1
Decitabine	affects expression, affects methylation	1
Benzo(a)pyrene	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	decreases methylation	1
Tobacco Smoke Pollution	affects expression	1
Isotretinoin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice