GNPDA1

Summary

GNPDA1 (glucosamine-6-phosphate deaminase 1, HGNC:4417) is a protein-coding gene on chromosome 5q31.3, encoding Glucosamine-6-phosphate deaminase 1 (P46926). Catalyzes the reversible conversion of alpha-D-glucosamine 6-phosphate (GlcN-6P) into beta-D-fructose 6-phosphate (Fru-6P) and ammonium ion, a regulatory reaction step in de novo uridine diphosphate-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc) biosynthesis via hexosamine pathway.

Glucosamine-6-phosphate deaminase (EC 3.5.99.6) is an allosteric enzyme that catalyzes the reversible conversion of D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium (Arreola et al., 2003 [PubMed 12965206]).

Source: NCBI Gene 10007 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hemolytic anemia due to glucophosphate isomerase deficiency (Strong, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 316 total — 17 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• MANE Select transcript: NM_005471

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4417
Approved symbol	GNPDA1
Name	glucosamine-6-phosphate deaminase 1
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	GNPDA, HLN, GPI, KIAA0060
Ensembl gene	ENSG00000113552
Ensembl biotype	protein_coding
OMIM	601798
Entrez	10007

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 33 protein_coding, 3 retained_intron

ENST00000311337, ENST00000500692, ENST00000503229, ENST00000503794, ENST00000504139, ENST00000504424, ENST00000505689, ENST00000507107, ENST00000507559, ENST00000508177, ENST00000510194, ENST00000513454, ENST00000515747, ENST00000862713, ENST00000862714, ENST00000862715, ENST00000862716, ENST00000862717, ENST00000862718, ENST00000862719, ENST00000862720, ENST00000862721, ENST00000862722, ENST00000862723, ENST00000862724, ENST00000862725, ENST00000862726, ENST00000862727, ENST00000927689, ENST00000927690, ENST00000927691, ENST00000927692, ENST00000927693, ENST00000927694, ENST00000951013, ENST00000951014

RefSeq mRNA: 1 — MANE Select: NM_005471 NM_005471

CCDS: CCDS4272

Canonical transcript exons

ENST00000311337 — 7 exons

Exon	Start	End
ENSE00000814330	142004932	142005116
ENSE00000814331	142006144	142006326
ENSE00001736194	142003088	142003262
ENSE00001859437	142000671	142002129
ENSE00002026826	142012995	142013027
ENSE00003572009	142011912	142012041
ENSE00003661135	142007799	142007900

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 96.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5371 / max 134.2239, expressed in 1782 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63879	16.3480	1779
203719	1.1891	772

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	96.01	gold quality
nephron tubule	UBERON:0001231	95.90	gold quality
adult organism	UBERON:0007023	95.70	gold quality
islet of Langerhans	UBERON:0000006	94.71	gold quality
ventricular zone	UBERON:0003053	94.29	gold quality
right adrenal gland cortex	UBERON:0035827	93.94	gold quality
right adrenal gland	UBERON:0001233	93.82	gold quality
kidney epithelium	UBERON:0004819	93.81	gold quality
pigmented layer of retina	UBERON:0001782	93.72	gold quality
retina	UBERON:0000966	93.70	gold quality
renal medulla	UBERON:0000362	93.67	gold quality
adrenal tissue	UBERON:0018303	93.57	gold quality
adult mammalian kidney	UBERON:0000082	93.31	gold quality
kidney	UBERON:0002113	93.00	gold quality
jejunal mucosa	UBERON:0000399	92.97	gold quality
metanephric glomerulus	UBERON:0004736	92.96	gold quality
left adrenal gland	UBERON:0001234	92.93	gold quality
renal glomerulus	UBERON:0000074	92.89	gold quality
duodenum	UBERON:0002114	92.82	gold quality
adrenal cortex	UBERON:0001235	92.72	gold quality
cortex of kidney	UBERON:0001225	92.70	gold quality
stromal cell of endometrium	CL:0002255	92.63	gold quality
adrenal gland	UBERON:0002369	92.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.50	gold quality
left adrenal gland cortex	UBERON:0035825	92.43	gold quality
ganglionic eminence	UBERON:0004023	92.39	gold quality
smooth muscle tissue	UBERON:0001135	92.34	gold quality
cartilage tissue	UBERON:0002418	92.18	gold quality
eye	UBERON:0000970	92.12	gold quality
embryo	UBERON:0000922	91.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting GNPDA1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4659A-3P	99.80	72.62	4248

Literature-anchored findings (GeneRIF, showing 4)

• identification, chromosomal localization and functional analysis of cDNA encoding GNPI/Oscillin homolog named GNPI2. (PMID:12616532)
• Sequence analysis and crystallographic structure of GNP1. (PMID:12965206)
• Allosteric kinetics of the isoform 1 of human glucosamine-6-phosphate deaminase. (PMID:21807125)
• 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)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnpda1	ENSDARG00000037307
mus_musculus	Gnpda1	ENSMUSG00000052102
rattus_norvegicus	Gnpda1	ENSRNOG00000047213
drosophila_melanogaster	Oscillin	FBGN0031717
caenorhabditis_elegans		WBGENE00011399

Paralogs (1): GNPDA2 (ENSG00000163281)

Protein

Protein identifiers

Glucosamine-6-phosphate deaminase 1 — P46926 (reviewed: P46926)

Alternative names: Glucosamine-6-phosphate isomerase 1, Protein oscillin

All UniProt accessions (7): P46926, D6R917, D6R9P4, D6RAY7, D6RB13, D6RFF8, D6RFK5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible conversion of alpha-D-glucosamine 6-phosphate (GlcN-6P) into beta-D-fructose 6-phosphate (Fru-6P) and ammonium ion, a regulatory reaction step in de novo uridine diphosphate-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc) biosynthesis via hexosamine pathway. Deamination is coupled to aldo-keto isomerization mediating the metabolic flux from UDP-GlcNAc toward Fru-6P. At high ammonium level can drive amination and isomerization of Fru-6P toward hexosamines and UDP-GlcNAc synthesis. Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and their effects on hyaluronan synthesis that occur during tissue remodeling. Seems to trigger calcium oscillations in mammalian eggs. These oscillations serve as the essential trigger for egg activation and early development of the embryo.

Subunit / interactions. Homohexamer.

Subcellular location. Cytoplasm.

Activity regulation. Allosterically activated by N-acetylglucosamine-6-phosphate (GlcNAc6P).

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

Similarity. Belongs to the glucosamine/galactosamine-6-phosphate isomerase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P46926-1	1	yes
P46926-2	2

RefSeq proteins (1): NP_005462* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004547	Glucosamine6P_isomerase	Family
IPR006148	Glc/Gal-6P_isomerase	Domain
IPR018321	Glucosamine6P_isomerase_CS	Conserved_site
IPR037171	NagB/RpiA_transferase-like	Homologous_superfamily

Pfam: PF01182

Enzyme classification (BRENDA):

• EC 3.5.99.6 — glucosamine-6-phosphate deaminase (BRENDA: 26 organisms, 33 substrates, 29 inhibitors, 103 Km, 48 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-GLUCOSAMINE 6-PHOSPHATE	0.041–17	51
ALPHA-D-GLUCOSAMINE 6-PHOSPHATE	0.24–45.2	15
D-FRUCTOSE 6-PHOSPHATE	1.1–36	14
NH4+	3.7–300	10
NH3	14–41.6	3
FRUCTOSE 6-PHOSPHATE	1.7	1
GLUCOSAMINE 6-PHOSPHATE	5	1

Catalyzed reactions (Rhea), 1 shown:

• alpha-D-glucosamine 6-phosphate + H2O = beta-D-fructose 6-phosphate + NH4(+) (RHEA:12172)

UniProt features (36 total): helix 17, strand 8, active site 4, modified residue 2, mutagenesis site 2, chain 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1NE7	X-RAY DIFFRACTION	1.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46926-F1	93.81	0.90

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 (4): 72 (proton acceptor; for enolization step); 141 (for ring-opening step); 143 (proton acceptor; for ring-opening step); 148 (for ring-opening step)

Post-translational modifications (2): 64, 161

Mutagenesis-validated functional residues (2):

Position	Phenotype
268–289	decreases hexamer stability and catalytic efficiency.
275–289	decreases catalytic efficiency.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70171	Glycolysis

MSigDB gene sets: 625 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_SINGLE_FERTILIZATION, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_RESPONSE_TO_MUSCLE_STRETCH, GOBP_RESPONSE_TO_IMMOBILIZATION_STRESS, GOCC_SECRETORY_GRANULE, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MENSE_HYPOXIA_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, MITSIADES_RESPONSE_TO_APLIDIN_DN

GO Biological Process (8): carbohydrate metabolic process (GO:0005975), D-glucosamine catabolic process (GO:0006043), N-acetylglucosamine catabolic process (GO:0006046), UDP-N-acetylglucosamine biosynthetic process (GO:0006048), generation of precursor metabolites and energy (GO:0006091), single fertilization (GO:0007338), N-acetylneuraminate catabolic process (GO:0019262), N-acetylglucosamine metabolic process (GO:0006044)

GO Molecular Function (5): glucosamine-6-phosphate deaminase activity (GO:0004342), isomerase activity (GO:0016853), identical protein binding (GO:0042802), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

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
glucosamine-containing compound catabolic process	2
catalytic activity	2
cellular anatomical structure	2
primary metabolic process	1
D-glucosamine metabolic process	1
N-acetylglucosamine metabolic process	1
UDP-N-acetylglucosamine metabolic process	1
nucleotide-sugar biosynthetic process	1
amino sugar biosynthetic process	1
metabolic process	1
fertilization	1
N-acetylneuraminate metabolic process	1
amino sugar catabolic process	1
carboxylic acid catabolic process	1
amino sugar metabolic process	1
deaminase activity	1
protein binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

1564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNPDA1	H6PD	O95479	840
GNPDA1	AMDHD2	Q9Y303	827
GNPDA1	H3BQ15	H3BQ15	826
GNPDA1	UAP1	Q16222	649
GNPDA1	GNPNAT1	Q96EK6	646
GNPDA1	GFPT2	O94808	630
GNPDA1	GFPT1	Q06210	630
GNPDA1	NAGK	Q9UJ70	623
GNPDA1	PGM3	O95394	585
GNPDA1	GALE	Q14376	513
GNPDA1	GPI	P06744	489
GNPDA1	TPI1	P00938	457
GNPDA1	GMPR	P36959	449
GNPDA1	GALK1	P51570	441
GNPDA1	HK1	P19367	431

IntAct

42 interactions, top by confidence:

A	B	Type	Score
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
GNPDA2	GNPDA1	psi-mi:“MI:0914”(association)	0.640
FAM174A	GAK	psi-mi:“MI:0914”(association)	0.640
GNPDA1	MAGEA11	psi-mi:“MI:0915”(physical association)	0.560
PRTFDC1	GNPDA1	psi-mi:“MI:0915”(physical association)	0.560
MAGEA11	GNPDA1	psi-mi:“MI:0915”(physical association)	0.560
GNPDA1	PRTFDC1	psi-mi:“MI:0915”(physical association)	0.560
FGL2	PCNT	psi-mi:“MI:0914”(association)	0.530
GPS1	PXDNL	psi-mi:“MI:0914”(association)	0.530
	TK2	psi-mi:“MI:0915”(physical association)	0.400
EWSR1	GNPDA1	psi-mi:“MI:0915”(physical association)	0.370
STK11	GNPDA1	psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
GNPDA1	SEC31A	psi-mi:“MI:0914”(association)	0.350
VAMP8	SCAMP1	psi-mi:“MI:0914”(association)	0.350
IGHD	POTEF	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
GNPDA1	ABLIM3	psi-mi:“MI:0914”(association)	0.350
IGHD	OBSL1	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
KIAA1191	UBA6	psi-mi:“MI:0914”(association)	0.350
LGALS9	CYB5A	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (81): GNPDA1 (Two-hybrid), PRTFDC1 (Two-hybrid), GNPDA1 (Affinity Capture-RNA), GNPDA1 (Affinity Capture-RNA), GNPDA2 (Affinity Capture-MS), AMDHD2 (Affinity Capture-MS), GNPDA1 (Affinity Capture-MS), GNPDA1 (Two-hybrid), ASS1 (Co-fractionation), GNPDA1 (Co-fractionation), GNPDA1 (Co-fractionation), GNPDA1 (Co-fractionation), GNPDA1 (Co-fractionation), TANGO2 (Co-fractionation), GNPDA1 (Two-hybrid)

ESM2 similar proteins: A0A0K9RL25, A0A0U1WZ18, A0A1S4A695, B9N1F9, O15305, O35621, O80840, O88958, O97555, O97556, P21856, P31150, P46926, P50396, P50398, P50399, P60028, P78330, Q16HW7, Q1W374, Q1W375, Q1W376, Q1W377, Q259G4, Q2KHU0, Q3SZJ9, Q3UFY7, Q4R7R3, Q5E982, Q5R8T8, Q5RB83, Q5ZID6, Q5ZKF6, Q60HD6, Q61598, Q64422, Q6AYP7, Q6Q7J2, Q7SYN4, Q7XPW5

Diamond homologs: A0KIG3, A1A8T7, A3N353, A4FV08, A4IHW6, A4SPM2, A4W844, A5F125, A6L7Q8, A6LHV2, A6T6C1, A7MQT6, A7N5W3, A7ZJ60, A7ZXT7, A8AJE0, A8GB41, A9MKA9, A9MUG8, B0BSS6, B0UUN2, B1IY50, B1LLC0, B1X6L1, B2RJ01, B2RZL5, B2TU53, B2VBN5, B3GZ06, B4SYN7, B4TB82, B4TPZ8, B5BCC5, B5EZC1, B5FBU7, B5FNB9, B5QWC8, B5R824, B5XZG9, B5YQM0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	13
Uncertain significance	144
Likely benign	56
Benign	15

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068750	NM_000175.5(GPI):c.286C>T (p.Arg96Ter)	Pathogenic
1176072	NM_000175.5(GPI):c.1414C>T (p.Arg472Cys)	Pathogenic
1323032	NM_000175.5(GPI):c.244del (p.Glu82fs)	Pathogenic
13642	NM_000175.5(GPI):c.1615G>A (p.Asp539Asn)	Pathogenic
13644	NM_000175.5(GPI):c.59A>C (p.His20Pro)	Pathogenic
13645	NM_000175.5(GPI):c.1016T>C (p.Leu339Pro)	Pathogenic
13646	NM_000175.5(GPI):c.1028A>G (p.Gln343Arg)	Pathogenic
13647	NM_000175.5(GPI):c.14C>T (p.Thr5Ile)	Pathogenic
13648	NM_000175.5(GPI):c.1124C>G (p.Thr375Arg)	Pathogenic
1679475	NM_000175.5(GPI):c.1144G>T (p.Glu382Ter)	Pathogenic
1697237	NM_000175.5(GPI):c.301G>A (p.Val101Met)	Pathogenic
2436673	NM_000175.5(GPI):c.1415G>A (p.Arg472His)	Pathogenic
2683541	NM_000175.5(GPI):c.818G>A (p.Arg273His)	Pathogenic
2705368	NM_000175.5(GPI):c.1140G>A (p.Trp380Ter)	Pathogenic
3339453	NC_000019.9:g.(34884972_34887205)(34893319?)del	Pathogenic
3602726	NM_000175.5(GPI):c.1010C>T (p.Ala337Val)	Pathogenic
4702959	NM_000175.5(GPI):c.259G>T (p.Gly87Cys)	Pathogenic
1697238	NM_000175.5(GPI):c.812del (p.Gly271fs)	Likely pathogenic
2432248	NM_000175.5(GPI):c.833C>T (p.Ser278Leu)	Likely pathogenic
2505370	NM_000175.5(GPI):c.283-2A>G	Likely pathogenic
2506149	NM_000175.5(GPI):c.1269+1G>A	Likely pathogenic
2585258	NM_000175.5(GPI):c.804+1_804+2del	Likely pathogenic
2690617	NM_000175.5(GPI):c.1498_1501del (p.Val500fs)	Likely pathogenic
2690618	NM_000175.5(GPI):c.937_952dup (p.Val318fs)	Likely pathogenic
3033365	NM_001289789.1(GPI):c.82C>T (p.Gln28Ter)	Likely pathogenic
3779707	NM_000175.5(GPI):c.48dup (p.Tyr17fs)	Likely pathogenic
4081434	NM_000175.5(GPI):c.866-1G>A	Likely pathogenic
4081435	NM_000175.5(GPI):c.1475-2A>G	Likely pathogenic
4081436	NM_000175.5(GPI):c.1162del (p.Gln388fs)	Likely pathogenic
4542338	NM_000175.5(GPI):c.838A>G (p.Ile280Val)	Likely pathogenic

SpliceAI

4304 predictions. Top by Δscore:

Variant	Effect	Δscore
19:34365369:G:GT	donor_gain	1.0000
19:34365386:CAGG:C	donor_loss	1.0000
19:34365387:AGGT:A	donor_loss	1.0000
19:34365389:GT:G	donor_loss	1.0000
19:34365390:T:G	donor_loss	1.0000
19:34366341:GCAG:G	acceptor_loss	1.0000
19:34366342:CAGC:C	acceptor_loss	1.0000
19:34366343:A:AC	acceptor_loss	1.0000
19:34366343:A:AG	acceptor_gain	1.0000
19:34366343:AGCTT:A	acceptor_gain	1.0000
19:34366344:G:GC	acceptor_gain	1.0000
19:34366344:GC:G	acceptor_gain	1.0000
19:34366344:GCT:G	acceptor_gain	1.0000
19:34366344:GCTT:G	acceptor_gain	1.0000
19:34366344:GCTTG:G	acceptor_gain	1.0000
19:34366409:G:GT	donor_gain	1.0000
19:34366428:T:TA	donor_gain	1.0000
19:34366432:CTTG:C	donor_loss	1.0000
19:34366433:TTGGT:T	donor_loss	1.0000
19:34366434:TG:T	donor_loss	1.0000
19:34366436:G:GA	donor_loss	1.0000
19:34366436:G:GG	donor_gain	1.0000
19:34366780:TA:T	acceptor_loss	1.0000
19:34366781:A:AG	acceptor_gain	1.0000
19:34366781:AG:A	acceptor_gain	1.0000
19:34366782:G:GG	acceptor_gain	1.0000
19:34366782:GG:G	acceptor_gain	1.0000
19:34366852:GT:G	donor_loss	1.0000
19:34368698:GCCAG:G	donor_gain	1.0000
19:34368701:AG:A	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000169409 (5:142008396 T>C), RS1000363633 (5:142001413 T>C), RS1000557263 (5:142013757 G>A), RS1000809671 (5:142007092 G>T), RS1000845197 (5:142003017 G>A,C), RS1000875378 (5:142008707 A>G), RS1000903293 (5:142006634 G>A), RS1001152123 (5:142001090 G>A), RS1001404179 (5:142009803 C>T), RS1001511089 (5:142014597 A>C), RS1002104945 (5:142013322 C>T), RS1002684083 (5:142005109 G>A,T), RS1002976132 (5:142006511 C>T), RS1003199069 (5:142012129 C>G), RS1003511805 (5:142011775 G>A)

Disease associations

OMIM: gene MIM:601798 | disease phenotypes: MIM:613470, MIM:615802

GenCC curated gene-disease

Disease	Classification	Inheritance
hemolytic anemia due to glucophosphate isomerase deficiency	Strong	Autosomal recessive

Mondo (4): hemolytic anemia due to glucophosphate isomerase deficiency (MONDO:0013275), hereditary spherocytosis (MONDO:0019350), intellectual disability, autosomal recessive 42 (MONDO:0014348), hemolytic anemia (MONDO:0003664)

Orphanet (3): Hemolytic anemia due to glucophosphate isomerase deficiency (Orphanet:712), Hereditary spherocytosis (Orphanet:822), Autosomal recessive non-syndromic intellectual disability (Orphanet:88616)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000952	Jaundice
HP:0001081	Cholelithiasis
HP:0001082	Cholecystitis
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001324	Muscle weakness
HP:0001744	Splenomegaly
HP:0001789	Hydrops fetalis
HP:0001923	Reticulocytosis
HP:0001930	Nonspherocytic hemolytic anemia
HP:0002240	Hepatomegaly
HP:0003568	Decreased glucosephosphate isomerase level
HP:0004447	Poikilocytosis
HP:0005525	Spontaneous hemolytic crises
HP:0008282	Unconjugated hyperbilirubinemia
HP:0010871	Sensory ataxia
HP:0011981	Pigment gallstones
HP:0011993	Impaired neutrophil bactericidal activity
HP:0025435	Increased circulating lactate dehydrogenase concentration

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004750_71	Squamous cell lung carcinoma	6.000000e-06
GCST006218_16	Erosive tooth wear (severe vs non-severe)	6.000000e-08
GCST006218_18	Erosive tooth wear (severe vs non-severe)	3.000000e-08
GCST006218_93	Erosive tooth wear (severe vs non-severe)	7.000000e-06
GCST006226_18	Erosive tooth wear (severe vs none or mild)	5.000000e-06
GCST006862_4	Asthma	9.000000e-10
GCST009798_63	Asthma	9.000000e-14
GCST010796_5374	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST90002392_95	Mean corpuscular volume	1.000000e-09
GCST90002395_466	Mean platelet volume	2.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000743	Anemia, Hemolytic	C15.378.050.141
D013103	Spherocytosis, Hereditary	C15.378.050.141.150.785; C16.320.070.785

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066890 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.07	Kd	8.474	nM	CHEMBL5653589
7.83	ED50	14.89	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148446: Binding affinity to human GNPDA1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0085	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, increases expression	3
Cadmium Chloride	increases abundance, increases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	decreases expression, increases expression	2
Arsenic	increases methylation, increases abundance, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases expression, increases abundance	1
salinomycin	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	affects cotreatment, affects expression	1
sulforaphane	increases expression	1
perfluorooctanoic acid	increases expression	1
triacsin C	decreases expression	1
brequinar	increases expression	1
diethyl malate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	increases expression	1
mono-benzyl phthalate	affects expression, affects cotreatment	1
deguelin	decreases expression	1
mono(2-ethyl-5-hydroxyhexyl) phthalate	affects cotreatment, affects expression, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
mono-isobutyl phthalate	affects cotreatment, affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651488	Binding	Binding affinity to human GNPDA1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2XY	Abcam HEK293T GNPDA1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05777993	PHASE4	ENROLLING_BY_INVITATION	A Study to Provide Continued Access to Mitapivat for Participants Who Previously Completed an Agios-Sponsored Mitapivat Study
NCT00001729	PHASE3	COMPLETED	Combination Drug Therapy for Patients With Hepatitis C
NCT03548220	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT03559699	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of AG-348 in Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT00110617	PHASE2	COMPLETED	Study of Deferasirox Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients
NCT01579110	PHASE2	UNKNOWN	Efficacy and Safety of Levamisole Combined With Standard Prednisolone in Warm Antibody Autoimmune Hemolytic Anemia.
NCT01642979	PHASE2	UNKNOWN	Safety and Efficacy of Levamisole Combined With Cyclosporine A in Patients With Classic Paroxysmal Nocturnal Hemoglobinuria
NCT01760096	PHASE2	UNKNOWN	Safety and Efficacy of Levamisole Combined With Cyclosporine A in Patients With Subclinical Paroxysmal Nocturnal Hemoglobinuria and PNH in the Setting of Another Bone Marrow Failure Syndromes(PNH-2013)
NCT05004259	PHASE1	COMPLETED	The Safety of Repurposing Daratumumab for Relapsed or Refractory Autoimmune Antibody Mediated Hemolytic Anemia
NCT06684041	PHASE1	COMPLETED	A Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Study, and QT Interval Study of HRS-5965 Capsules in Healthy Subjects
NCT07040787	PHASE1	COMPLETED	Investigation of Drug-drug Interaction of HRS-5965 With Clopidogrel and Clarithromycin in Healthy Subjects
NCT01141621	Not specified	TERMINATED	The Dallas Hereditary Spherocytosis Cohort Study
NCT01276561	Not specified	WITHDRAWN	Single Incision Versus Standard Laparoscopic Splenectomy
NCT04451785	Not specified	COMPLETED	Hereditary Spherocytosis and Vascular Function
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT04610866	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
NCT00842621	Not specified	COMPLETED	Long Term Effects of Erythrocyte Lysis
NCT00971984	Not specified	COMPLETED	Demographic, Clinical and Laboratory Characteristics of Children With Alpha Thalassemia in Northern Israel
NCT02111590	Not specified	COMPLETED	Immunoglobulin Dosage and Administration Form in CIDP and MMN
NCT03006718	Not specified	COMPLETED	SCD-PROMIS: A Software Platform to Enhance Self-efficacy and Patient-provider Engagement for Patients With Sickle Cell Pain
NCT04721262	Not specified	COMPLETED	Ferumoxytol Enhanced Hyperfine Low Field Strength MRI
NCT04964323	Not specified	TERMINATED	Pyruvate Kinase (PK) Deficiency Global Longitudinal Registry: Patient-Reported Outcomes (PRO)
NCT06708728	Not specified	NOT_YET_RECRUITING	Study of Acquired Hemolytic Anemia in Adult Hospitalized Patients