GFPT2

Summary

GFPT2 (glutamine–fructose-6-phosphate transaminase 2, HGNC:4242) is a protein-coding gene on chromosome 5q35.3, encoding Glutamine–fructose-6-phosphate aminotransferase [isomerizing] 2 (O94808). Rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) that catalyzes the formation of glucosamine-6-phosphate from fructose-6-phosphate and glutamine, thereby controlling the flux of glucose into this pathway.

Enables glutamine-fructose-6-phosphate transaminase (isomerizing) activity. Involved in UDP-N-acetylglucosamine biosynthetic process and fructose 6-phosphate metabolic process. Predicted to be located in cytosol. Implicated in type 2 diabetes mellitus.

Source: NCBI Gene 9945 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 112 total
• MANE Select transcript: NM_005110

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4242
Approved symbol	GFPT2
Name	glutamine–fructose-6-phosphate transaminase 2
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	GFAT2
Ensembl gene	ENSG00000131459
Ensembl biotype	protein_coding
OMIM	603865
Entrez	9945

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000253778, ENST00000503228, ENST00000503546, ENST00000510122, ENST00000518158, ENST00000518185, ENST00000518906, ENST00000520165, ENST00000889625, ENST00000889626, ENST00000889627, ENST00000920226, ENST00000920227, ENST00000920228, ENST00000920229, ENST00000920230, ENST00000953747, ENST00000953748

RefSeq mRNA: 1 — MANE Select: NM_005110 NM_005110

CCDS: CCDS43411

Canonical transcript exons

ENST00000253778 — 19 exons

Exon	Start	End
ENSE00000770431	180304772	180304939
ENSE00000770433	180307176	180307303
ENSE00000770435	180312430	180312544
ENSE00000770437	180313807	180313964
ENSE00000770453	180330700	180330834
ENSE00000770455	180331495	180331553
ENSE00000827568	180302423	180302584
ENSE00001096008	180300698	180301608
ENSE00002089809	180353211	180353336
ENSE00002480812	180316341	180316461
ENSE00003483941	180328277	180328338
ENSE00003503691	180338493	180338600
ENSE00003504216	180336479	180336577
ENSE00003593034	180324816	180324895
ENSE00003611459	180318793	180318956
ENSE00003630115	180316963	180317058
ENSE00003656015	180335828	180335953
ENSE00003677289	180324188	180324305
ENSE00003684026	180316764	180316861

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 96.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3894 / max 609.1864, expressed in 1250 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65295	16.8325	1237
65290	0.3107	110
65293	0.0899	20
65291	0.0758	22
65292	0.0496	11
65294	0.0309	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	96.28	gold quality
omental fat pad	UBERON:0010414	95.66	gold quality
peritoneum	UBERON:0002358	95.61	gold quality
synovial joint	UBERON:0002217	94.94	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.37	gold quality
left uterine tube	UBERON:0001303	93.92	gold quality
right ovary	UBERON:0002118	93.15	gold quality
left ovary	UBERON:0002119	92.37	gold quality
germinal epithelium of ovary	UBERON:0001304	92.33	gold quality
layer of synovial tissue	UBERON:0007616	91.92	gold quality
stromal cell of endometrium	CL:0002255	91.75	gold quality
parietal pleura	UBERON:0002400	91.65	gold quality
cartilage tissue	UBERON:0002418	90.70	gold quality
endocervix	UBERON:0000458	90.24	gold quality
calcaneal tendon	UBERON:0003701	89.65	gold quality
sural nerve	UBERON:0015488	89.49	gold quality
tendon of biceps brachii	UBERON:0008188	89.44	gold quality
apex of heart	UBERON:0002098	89.43	gold quality
tibial nerve	UBERON:0001323	89.32	gold quality
tibia	UBERON:0000979	89.16	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.83	gold quality
ovary	UBERON:0000992	88.75	gold quality
lower esophagus	UBERON:0013473	88.73	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.55	gold quality
mucosa of stomach	UBERON:0001199	88.28	gold quality
gall bladder	UBERON:0002110	87.96	gold quality
right atrium auricular region	UBERON:0006631	87.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.77	gold quality
cerebellar hemisphere	UBERON:0002245	87.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	279.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting GFPT2, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486

Literature-anchored findings (GeneRIF, showing 15)

• GFPT2 mRNA levels in transformed lymphocytes significantly increased among African-Americans. Associated allele of 3’ UTR SNP approximately 2-fold overexpressed. 3’ UTR variant results in increased GFPT2 mRNA with resultant increased hexosamine flux. (PMID:14764791)
• Increased GFAT activity appears to be associated with insulin resistance, postprandial hyperglycaemia and oxidative stress in T2DM and may point towards a potential pathway amenable for therapeutic intervention. (PMID:17574229)
• association of nine single nucleotide polymorphisms in ADPRT1, AKR1B1), RAGE, GFPT2 and PAI-1 genes with chronic renal insufficiency among Asian Indians with type 2 diabetes (PMID:20353610)
• GNPDA1 siRNA induced GFAT2 which was hardly measurable in these cells under standard culture conditions, GNPDA2 siRNA increased GFAT1, and GFAT1 siRNA increased the expression of hyaluronan synthase 2 (HAS2). Silencing of GFAT1 stimulated GNPDA1 and GDPDA2, and inhibited cell migration. (PMID:26887390)
• Transcriptome analysis of human primary non-small cell lung cancer specimens showed that glucose uptake associated with GFPT2-expressing cancer-associated fibroblasts was prognostic for adenocarcinoma. GFPT2 was predictive of glucose uptake independent of GLUT1, the primary glucose transporter, and was prognostically significant at both gene and protein level. (PMID:29760045)
• PPP2R2A interacts with GFPT1/2, and leads to the phosphorylation of GFPT2, which can regulate the cellular O-GlcNAcylation in breast cancer (PMID:29943541)
• Homozygosity of the GFPT2 p.Arg366Gln mutation was associated with increased levels of reactive oxygen species (ROS) in spermatozoa and decreased sperm motility. (PMID:30849544)
• Elevated GFPT2 expression correlates with poor clinical outcome in non-small cell lung cancer. (PMID:30885209)
• Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) activates the hexosamine biosynthetic pathway to increase the nuclear location of beta-catenin and promote epithelial-mesenchymal transformation of serous ovarian cancer. (PMID:31685298)
• Enzymatic and structural properties of human glutamine:fructose-6-phosphate amidotransferase 2 (hGFAT2). (PMID:33303629)
• Stomatinlike protein 2 induces metastasis by regulating the expression of a ratelimiting enzyme of the hexosamine biosynthetic pathway in pancreatic cancer. (PMID:33846782)
• Cardiomyocyte protein O-GlcNAcylation is regulated by GFAT1 not GFAT2. (PMID:34735873)
• Glutamine-Fructose-6-Phosphate Transaminase 2 (GFPT2) Is Upregulated in Breast Epithelial-Mesenchymal Transition and Responds to Oxidative Stress. (PMID:34923141)
• VCAM-1 and GFPT-2: Predictive markers of osteoblast differentiation in human dental pulp stem cells. (PMID:36195245)
• GFPT2: A novel biomarker in mesothelioma for diagnosis and prognosis and its molecular mechanism in malignant progression. (PMID:39317702)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gfpt2	ENSDARG00000044094
mus_musculus	Gfpt2	ENSMUSG00000020363
rattus_norvegicus	Gfpt2	ENSRNOG00000002810
drosophila_melanogaster	Gfat2	FBGN0039580
drosophila_melanogaster	Gfat1	FBGN0287209

Paralogs (1): GFPT1 (ENSG00000198380)

Protein

Protein identifiers

Glutamine–fructose-6-phosphate aminotransferase [isomerizing] 2 — O94808 (reviewed: O94808)

Alternative names: D-fructose-6-phosphate amidotransferase 2, Glutamine:fructose-6-phosphate amidotransferase 2, Hexosephosphate aminotransferase 2

All UniProt accessions (5): A0A0S2Z4W6, A0A0S2Z4X9, D6RAC1, E5RJP4, O94808

UniProt curated annotations — full annotation on UniProt →

Function. Rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) that catalyzes the formation of glucosamine-6-phosphate from fructose-6-phosphate and glutamine, thereby controlling the flux of glucose into this pathway. Via control of the HPB, likely regulates the availability of precursors for N- and O-linked protein glycosylation. Exhibits feedback inhibition by UDP-N-acetylglucosamine (UDP-GlcNAc), although to a lesser extent than GFPT1.

Tissue specificity. Predominantly expressed throughout the central nervous system, especially in the spinal cord. Also highly expressed in heart and placenta.

Activity regulation. Inhibited by UDP-GlcNAc.

Pathway. Nucleotide-sugar biosynthesis; UDP-N-acetyl-alpha-D-glucosamine biosynthesis; alpha-D-glucosamine 6-phosphate from D-fructose 6-phosphate: step 1/1.

RefSeq proteins (1): NP_005101* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001347	SIS_dom	Domain
IPR005855	GFAT	Family
IPR017932	GATase_2_dom	Domain
IPR029055	Ntn_hydrolases_N	Homologous_superfamily
IPR035466	GlmS/AgaS_SIS	Domain
IPR035490	GlmS/FrlB_SIS	Domain
IPR046348	SIS_dom_sf	Homologous_superfamily
IPR047084	GFAT_N	Domain

Pfam: PF01380, PF13522

Catalyzed reactions (Rhea), 1 shown:

• D-fructose 6-phosphate + L-glutamine = D-glucosamine 6-phosphate + L-glutamate (RHEA:13237)

UniProt features (31 total): binding site 23, domain 3, initiator methionine 1, chain 1, modified residue 1, sequence variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94808-F1	92.52	0.84

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): 2 (glutamine amidotransferase activity)

Ligand- & substrate-binding residues (23): 96; 105; 121; 145; 311; 344; 356; 377; 378; 422; 423; 424 …

Post-translational modifications (1): 244

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-446210	Synthesis of UDP-N-acetyl-glucosamine

MSigDB gene sets: 244 (showing top): GOBP_RESPONSE_TO_PEPTIDE, PEREZ_TP63_TARGETS, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, MODULE_45, GNF2_PTX3, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_AMINO_SUGAR_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, CTATGCA_MIR153, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, MODULE_66, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY

GO Biological Process (9): fructose 6-phosphate metabolic process (GO:0006002), UDP-N-acetylglucosamine metabolic process (GO:0006047), UDP-N-acetylglucosamine biosynthetic process (GO:0006048), energy reserve metabolic process (GO:0006112), protein N-linked glycosylation (GO:0006487), cellular response to leukemia inhibitory factor (GO:1990830), amino sugar biosynthetic process (GO:0046349), carbohydrate derivative metabolic process (GO:1901135), carbohydrate derivative biosynthetic process (GO:1901137)

GO Molecular Function (5): L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity (GO:0004360), carbohydrate derivative binding (GO:0097367), protein binding (GO:0005515), transaminase activity (GO:0008483), transferase activity (GO:0016740)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carbohydrate derivative metabolic process	2
amino sugar metabolic process	2
binding	2
organophosphate metabolic process	1
nucleotide-sugar metabolic process	1
UDP-N-acetylglucosamine metabolic process	1
nucleotide-sugar biosynthetic process	1
amino sugar biosynthetic process	1
energy derivation by oxidation of organic compounds	1
glycoprotein biosynthetic process	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
carbohydrate derivative biosynthetic process	1
metabolic process	1
biosynthetic process	1
amino acid transaminase activity	1
transferase activity, transferring nitrogenous groups	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GFPT2	GNPNAT1	Q96EK6	770
GFPT2	UAP1	Q16222	769
GFPT2	OGA	O60502	758
GFPT2	PGM3	O95394	731
GFPT2	OGT	O15294	702
GFPT2	GNPDA1	P46926	630
GFPT2	NAGK	Q9UJ70	629
GFPT2	GPI	P06744	579
GFPT2	AMDHD2	Q9Y303	549
GFPT2	GNPDA2	Q8TDQ7	548
GFPT2	H6PD	O95479	531
GFPT2	H3BQ15	H3BQ15	528
GFPT2	GMPS	P49915	504
GFPT2	GLUL	P15104	483
GFPT2	UAP1L1	Q3KQV9	477

IntAct

56 interactions, top by confidence:

A	B	Type	Score
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.960
TUBA1C	TXNDC9	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GFPT2	GFPT1	psi-mi:“MI:0915”(physical association)	0.620
GFPT2	GFPT1	psi-mi:“MI:0914”(association)	0.620
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
DKK3	NME4	psi-mi:“MI:0914”(association)	0.530
SALL2	GFPT2	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
POT1	GFPT2	psi-mi:“MI:0915”(physical association)	0.510
	TK2	psi-mi:“MI:0915”(physical association)	0.400
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
SLAMF1	RTCA	psi-mi:“MI:0914”(association)	0.350
GFPT2	GFPT1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
HNF1B	GFPT2	psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
SV2A	ILVBL	psi-mi:“MI:0914”(association)	0.350
LURAP1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
DKK3	MYO9A	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): GFPT2 (Affinity Capture-MS), GFPT2 (Affinity Capture-MS), GFPT2 (Affinity Capture-MS), GFPT2 (Affinity Capture-MS), GFPT2 (Affinity Capture-MS), GFPT2 (Affinity Capture-MS), GFPT2 (Affinity Capture-MS), CCT8 (Co-fractionation), GFPT2 (Co-fractionation), GFPT2 (Co-fractionation), GFPT2 (Co-fractionation), GFPT2 (Co-fractionation), GFPT2 (Co-fractionation), GFPT2 (Co-fractionation), GFPT2 (Co-fractionation)

ESM2 similar proteins: A8EZA9, A8F1A5, A8GN21, A8GRN9, A8GWP0, A8Y0L5, B9J8R3, O25511, O45583, O60547, O94808, P0AC88, P0AC89, P0AC90, P0AC91, P12378, P39858, P46320, P93031, Q06952, Q08DQ2, Q0P8I7, Q0P8W4, Q18801, Q1RIM4, Q1ZXF7, Q24PE3, Q48154, Q48230, Q4KMC4, Q4UM33, Q56598, Q56872, Q59678, Q5QKR8, Q8K0C9, Q8K3X3, Q8L2J6, Q8RIA5, Q92IG3

Diamond homologs: A2P2R3, A6ZME2, B3LLX6, C7GL41, C8ZET7, O26060, O26273, O57981, O66648, O68280, O68956, O83833, O86781, O94808, P14742, P17169, P44708, P47856, P53704, P57138, P57963, P59499, P72720, P82808, P94323, Q06210, Q08DQ2, Q09740, Q4KMC4, Q56213, Q56275, Q5E279, Q5JH71, Q5L3P0, Q5L589, Q5NHQ9, Q5NRH4, Q5PKV9, Q5QZH5, Q663R1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	88
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2552 predictions. Top by Δscore:

Variant	Effect	Δscore
5:180302421:A:AC	donor_gain	1.0000
5:180302422:C:CC	donor_gain	1.0000
5:180302428:AT:A	donor_gain	1.0000
5:180304766:CCTCA:C	donor_loss	1.0000
5:180304767:CTCA:C	donor_loss	1.0000
5:180304768:TCA:T	donor_loss	1.0000
5:180304769:CAC:C	donor_loss	1.0000
5:180304770:A:C	donor_loss	1.0000
5:180304935:ATTTT:A	acceptor_gain	1.0000
5:180304936:TTTT:T	acceptor_gain	1.0000
5:180304937:TTT:T	acceptor_gain	1.0000
5:180304938:TT:T	acceptor_gain	1.0000
5:180307170:GCTCA:G	donor_loss	1.0000
5:180307171:CTCA:C	donor_loss	1.0000
5:180307172:TCACC:T	donor_loss	1.0000
5:180307173:CACC:C	donor_loss	1.0000
5:180307174:A:AG	donor_loss	1.0000
5:180307175:C:CA	donor_loss	1.0000
5:180307186:T:TA	donor_gain	1.0000
5:180307299:CAGCT:C	acceptor_gain	1.0000
5:180307302:CT:C	acceptor_gain	1.0000
5:180307309:CCA:C	acceptor_gain	1.0000
5:180307310:C:T	acceptor_gain	1.0000
5:180307310:CA:C	acceptor_gain	1.0000
5:180307311:A:AC	acceptor_gain	1.0000
5:180307311:A:C	acceptor_gain	1.0000
5:180307311:A:T	acceptor_gain	1.0000
5:180307314:C:CT	acceptor_gain	1.0000
5:180307316:C:CT	acceptor_gain	1.0000
5:180307317:G:T	acceptor_gain	1.0000

AlphaMissense

4489 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:180304878:C:T	G579E	1.000
5:180304883:C:A	K577N	1.000
5:180304883:C:G	K577N	1.000
5:180304887:A:G	L576P	1.000
5:180307177:A:G	L558P	1.000
5:180312533:A:C	S481R	1.000
5:180312533:A:T	S481R	1.000
5:180312535:T:G	S481R	1.000
5:180313813:G:C	S475R	1.000
5:180313813:G:T	S475R	1.000
5:180313815:T:G	S475R	1.000
5:180313817:G:T	A474D	1.000
5:180313891:G:C	N449K	1.000
5:180313891:G:T	N449K	1.000
5:180313964:C:A	G425V	1.000
5:180313964:C:T	G425D	1.000
5:180316348:G:C	S422R	1.000
5:180316348:G:T	S422R	1.000
5:180316350:T:G	S422R	1.000
5:180316782:G:C	S378R	1.000
5:180316782:G:T	S378R	1.000
5:180316784:T:G	S378R	1.000
5:180330779:A:G	L152P	1.000
5:180331532:C:T	G121E	1.000
5:180331533:C:A	G121W	1.000
5:180335851:G:T	P106H	1.000
5:180335889:C:A	W93C	1.000
5:180335889:C:G	W93C	1.000
5:180335891:A:G	W93R	1.000
5:180335891:A:T	W93R	1.000

dbSNP variants (sampled 300 via entrez): RS1000010701 (5:180321029 G>A,T), RS1000231077 (5:180309150 G>A), RS1000237122 (5:180353856 G>T), RS1000271017 (5:180336349 G>A,C,T), RS1000302009 (5:180303908 G>A,C), RS1000361224 (5:180326364 A>G), RS1000423823 (5:180331831 G>A,T), RS1000457491 (5:180332914 A>C), RS1000482736 (5:180314080 C>G,T), RS1000510896 (5:180301677 T>A,C), RS1000562183 (5:180310481 G>A), RS1000612997 (5:180330385 C>A), RS1000637800 (5:180308021 C>A), RS1000740672 (5:180335589 C>T), RS1000774129 (5:180339472 G>T)

Disease associations

OMIM: gene MIM:603865 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000817_130	Height	2.000000e-09
GCST001343_14	Fat distribution (HIV)	2.000000e-06
GCST004525_6	Subclinical trait of interstitial lung disease (basilar peel-core ratio of high attentuation areas on CT scan)	5.000000e-11
GCST012227_215	Hip circumference adjusted for BMI	3.000000e-09
GCST012490_389	Femur bone mineral density x serum urate levels interaction	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0007627	airway imaging measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, affects cotreatment, increases abundance, increases expression	4
Valproic Acid	affects expression, increases expression, increases methylation	4
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Nickel	increases expression	2
Silicon Dioxide	increases expression	2
Tretinoin	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
methyleugenol	increases expression	1
bisphenol A	decreases methylation, affects cotreatment	1
trichostatin A	increases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders