TALDO1

Summary

TALDO1 (transaldolase 1, HGNC:11559) is a protein-coding gene on chromosome 11p15.5, encoding Transaldolase (P37837). Catalyzes the rate-limiting step of the non-oxidative phase in the pentose phosphate pathway.

Transaldolase 1 is a key enzyme of the nonoxidative pentose phosphate pathway providing ribose-5-phosphate for nucleic acid synthesis and NADPH for lipid biosynthesis. This pathway can also maintain glutathione at a reduced state and thus protect sulfhydryl groups and cellular integrity from oxygen radicals. The functional gene of transaldolase 1 is located on chromosome 11 and a pseudogene is identified on chromosome 1 but there are conflicting map locations. The second and third exon of this gene were developed by insertion of a retrotransposable element. This gene is thought to be involved in multiple sclerosis.

Source: NCBI Gene 6888 — RefSeq curated summary.

At a glance

• Gene–disease (curated): transaldolase deficiency (Definitive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 249 total — 16 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 45
• Druggable target: yes
• MANE Select transcript: NM_006755

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11559
Approved symbol	TALDO1
Name	transaldolase 1
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000177156
Ensembl biotype	protein_coding
OMIM	602063
Entrez	6888

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000319006, ENST00000528070, ENST00000528097, ENST00000530119, ENST00000530440, ENST00000530666, ENST00000532202, ENST00000532685, ENST00000533796, ENST00000896394, ENST00000896395, ENST00000896396, ENST00000896397, ENST00000933598, ENST00000933599

RefSeq mRNA: 1 — MANE Select: NM_006755 NM_006755

CCDS: CCDS7712

Canonical transcript exons

ENST00000319006 — 8 exons

Exon	Start	End
ENSE00001259140	763747	763944
ENSE00001259169	764813	765012
ENSE00001297974	747464	747578
ENSE00003511489	763344	763519
ENSE00003595520	755879	756002
ENSE00003626202	760122	760253
ENSE00003648364	758950	759057
ENSE00003663699	764288	764433

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 235.0383 / max 2653.7750, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112250	235.0383	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.58	gold quality
blood	UBERON:0000178	99.54	gold quality
gingival epithelium	UBERON:0001949	99.50	gold quality
gingiva	UBERON:0001828	99.49	gold quality
esophagus squamous epithelium	UBERON:0006920	99.41	gold quality
oocyte	CL:0000023	99.39	gold quality
lower esophagus mucosa	UBERON:0035834	99.37	gold quality
monocyte	CL:0000576	99.34	gold quality
epithelium of esophagus	UBERON:0001976	99.31	gold quality
bone marrow	UBERON:0002371	99.31	gold quality
oral cavity	UBERON:0000167	99.30	gold quality
leukocyte	CL:0000738	99.29	gold quality
mononuclear cell	CL:0000842	99.29	gold quality
esophagus mucosa	UBERON:0002469	99.18	gold quality
palpebral conjunctiva	UBERON:0001812	99.17	gold quality
secondary oocyte	CL:0000655	99.10	gold quality
granulocyte	CL:0000094	99.08	gold quality
pharyngeal mucosa	UBERON:0000355	98.99	gold quality
bronchial epithelial cell	CL:0002328	98.96	gold quality
tongue squamous epithelium	UBERON:0006919	98.88	gold quality
periodontal ligament	UBERON:0008266	98.81	gold quality
right lobe of thyroid gland	UBERON:0001119	98.80	gold quality
mammalian vulva	UBERON:0000997	98.78	gold quality
bone marrow cell	CL:0002092	98.77	gold quality
epithelium of bronchus	UBERON:0002031	98.76	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.76	gold quality
bronchus	UBERON:0002185	98.74	gold quality
esophagus	UBERON:0001043	98.65	gold quality
left lobe of thyroid gland	UBERON:0001120	98.60	gold quality
squamous epithelium	UBERON:0006914	98.55	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	910.05
E-CURD-122	yes	69.22
E-MTAB-6678	yes	25.02
E-HCAD-6	yes	19.93
E-MTAB-9801	yes	7.79
E-HCAD-9	yes	6.64
E-MTAB-6911	no	290.69
E-CURD-88	no	3.69
E-MTAB-5061	no	3.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFE2L2, TFAP2A, ZNF143, ZNF76

miRNA regulators (miRDB)

2 targeting TALDO1, 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-2115-3P	99.31	69.68	2026
HSA-MIR-6849-3P	97.25	64.57	1371

Literature-anchored findings (GeneRIF, showing 21)

• transaldolase is regulated by ZNF143 in a tissue-specific manner (PMID:14702349)
• TALase undergoes anterograde trafficking in neutrophils from nonpregnant individuals, whereas retrograde trafficking is found during pregnancy (PMID:16092052)
• Mutation in the TALDO1 gene was found in patients with hydrops fetalis and neonatal multi-organ disease. (PMID:17095351)
• A patch of functionally important amino acid residues extends from serine-171 toward the catalytic site and is proposed as a novel ligand shuttling path connecting these specific sites to the enzyme’s active site. (PMID:17503352)
• Transaldolase-deficient patients had significantly increased urinary heptoses, revealing novel urinary biomarkers for identification of the deficiency. (PMID:17603756)
• A new case of TALDO deficiency resulted in cirrhosis, rickets and deafness. (PMID:18331807)
• The present study identified the TAL deficiency as a modulator of mitochondrial homoeostasis, Ca(2+) fluxing and apoptosis. (PMID:18498245)
• analysis of enzymes TalB and Taldo1 in human and E. coli (PMID:18687684)
• genetic polymorphisms in Transaldolase 1 are associated with squamous cell carcinoma of the head and neck . (PMID:18805652)
• granzyme B-cleaved transaldolase-specific T cell-mediated cytotoxicity may contribute to the progressive destruction of oligodendrocytes in patients with multiple sclerosis (PMID:20194725)
• Data show that erythronic acid was identified as a major abnormal metabolite in all patients and in knock-out TALDO mice implicating an as yet unknown biochemical pathway in this disease. (PMID:20600873)
• these data provide strong experimental evidence that transaldolase exchange occurs in humans, resulting in an overestimate of gluconeogenesis (PMID:21062960)
• renal phenotype of patients with transaldolase deficiency (PMID:22510381)
• This study expands the clinical definition of transaldolase deficiency, and adds to its allelic heterogeneity. (PMID:23315216)
• Data suggest that exchange reactions during gluconeogenesis catalyzed by transaldolase and triose-phosphate isomerase do not differ between subjects with type 2 diabetes and control subjects under fasting or hyperglycemic conditions. (PMID:23736541)
• The above findings support the premise that biallelic mutations in TALDO1 are responsible for transaldolase deficiency and confirm the broad phenotypic variability of this condition, even with the same genotype. (PMID:25388407)
• These results demonstrate that the nucleocytoplasmic distribution of TALDO1, modulated via alternative translational initiation and dimer formation, plays an important role in a wide range of metabolic networks (PMID:27703206)
• these results pinpoint transaldolase as a novel metabolic enzyme possessing synthetic lethality with HER2 inhibition. (PMID:30323337)
• Untargeted metabolomics as an unbiased approach to the diagnosis of inborn errors of metabolism of the non-oxidative branch of the pentose phosphate pathway. (PMID:32828637)
• SLC1A5 co-expression with TALDO1 associates with endocrine therapy failure in estrogen receptor-positive breast cancer. (PMID:34282517)
• Liver Disease and Risk of Hepatocellular Carcinoma in Children With Mutations in TALDO1. (PMID:34677006)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	taldo1	ENSDARG00000103369
mus_musculus	Taldo1	ENSMUSG00000025503
rattus_norvegicus	Taldo1	ENSRNOG00000018367
drosophila_melanogaster	Taldo	FBGN0023477
caenorhabditis_elegans		WBGENE00021286

Protein

Protein identifiers

Transaldolase — P37837 (reviewed: P37837)

All UniProt accessions (5): P37837, A0A140VK56, E9PKI8, E9PM01, F2Z393

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the rate-limiting step of the non-oxidative phase in the pentose phosphate pathway. Catalyzes the reversible conversion of sedheptulose-7-phosphate and D-glyceraldehyde 3-phosphate into erythrose-4-phosphate and beta-D-fructose 6-phosphate. Not only acts as a pentose phosphate pathway enzyme, but also affects other metabolite pathways by altering its subcellular localization between the nucleus and the cytoplasm.

Subunit / interactions. Homodimer. Heterodimer with isoform 2. Interacts with KPNA1 and KPNA4.

Subcellular location. Nucleus. Cytoplasm Cytoplasm.

Disease relevance. Transaldolase deficiency (TALDOD) [MIM:606003] An inborn error of the pentose phosphate pathway resulting in early-onset multisystem disease. Clinical features include growth retardation, dysmorphic features, cutis laxa, congenital heart disease, hepatosplenomegaly, telangiectases of the skin, pancytopenia, and bleeding tendency. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The first 10 amino acids are essential for nuclear localization.

Pathway. Carbohydrate degradation; pentose phosphate pathway; D-glyceraldehyde 3-phosphate and beta-D-fructose 6-phosphate from D-ribose 5-phosphate and D-xylulose 5-phosphate (non-oxidative stage): step 2/3.

Similarity. Belongs to the transaldolase family. Type 1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P37837-1	1, TALDO1L	yes
P37837-2	2, TALDO1S

RefSeq proteins (1): NP_006746* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001585	TAL/FSA	Family
IPR004730	Transaldolase_1	Family
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR018225	Transaldolase_AS	Active_site

Pfam: PF00923

Catalyzed reactions (Rhea), 1 shown:

• D-sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = D-erythrose 4-phosphate + beta-D-fructose 6-phosphate (RHEA:17053)

UniProt features (43 total): helix 19, strand 8, modified residue 7, sequence variant 2, turn 2, chain 1, short sequence motif 1, splice variant 1, mutagenesis site 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1F05	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P37837-F1	95.63	0.95

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): 142 (schiff-base intermediate with substrate)

Post-translational modifications (7): 115, 219, 237, 256, 269, 286, 321

Mutagenesis-validated functional residues (1):

Position	Phenotype
189	confers fructose-6-phosphate aldolase activity.

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-163754	Insulin effects increased synthesis of Xylulose-5-Phosphate
R-HSA-6791055	TALDO1 deficiency: failed conversion of SH7P, GA3P to Fru(6)P, E4P
R-HSA-6791462	TALDO1 deficiency: failed conversion of Fru(6)P, E4P to SH7P, GA3P
R-HSA-71336	Pentose phosphate pathway
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-9818028	NFE2L2 regulates pentose phosphate pathway genes
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-2262752	Cellular responses to stress
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-5663084	Diseases of carbohydrate metabolism
R-HSA-5668914	Diseases of metabolism
R-HSA-6791465	Pentose phosphate pathway disease
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9020591	Interleukin-12 signaling
R-HSA-9711123	Cellular response to chemical stress
R-HSA-9755511	KEAP1-NFE2L2 pathway
R-HSA-9759194	Nuclear events mediated by NFE2L2

MSigDB gene sets: 335 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_NADPPLUS_METABOLIC_PROCESS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_GLUCOSE_6_PHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, ZHAN_V2_LATE_DIFFERENTIATION_GENES, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, KEGG_PENTOSE_PHOSPHATE_PATHWAY, GOBP_ALDEHYDE_METABOLIC_PROCESS, BENPORATH_NOS_TARGETS, RUAN_RESPONSE_TO_TROGLITAZONE_UP, RUAN_RESPONSE_TO_TNF_DN

GO Biological Process (5): carbohydrate metabolic process (GO:0005975), fructose 6-phosphate metabolic process (GO:0006002), pentose-phosphate shunt, non-oxidative branch (GO:0009052), pentose-phosphate shunt (GO:0006098), glyceraldehyde-3-phosphate metabolic process (GO:0019682)

GO Molecular Function (5): transaldolase activity (GO:0004801), monosaccharide binding (GO:0048029), protein binding (GO:0005515), transferase activity (GO:0016740), carbohydrate binding (GO:0030246)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Pentose phosphate pathway disease	2
Metabolism	2
Integration of energy metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Interleukin-12 signaling	1
Nuclear events mediated by NFE2L2	1
Immune System	1
Cellular responses to stimuli	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Diseases of metabolism	1
Disease	1
Diseases of carbohydrate metabolism	1
Interleukin-12 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organophosphate metabolic process	2
carbohydrate derivative metabolic process	2
binding	2
cellular anatomical structure	2
primary metabolic process	1
D-ribulose-phosphate 3-epimerase activity	1
ribose-5-phosphate isomerase activity	1
transaldolase activity	1
transketolase activity	1
generation of precursor metabolites and energy	1
pentose-phosphate shunt	1
glyceraldehyde-3-phosphate metabolic process	1
NADPH regeneration	1
pentose-phosphate shunt, oxidative branch	1
pentose-phosphate shunt, non-oxidative branch	1
glucose 6-phosphate metabolic process	1
aldehyde metabolic process	1
transketolase or transaldolase activity	1
carbohydrate binding	1
small molecule binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

3526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TALDO1	RPIA	P49247	992
TALDO1	TKTL2	Q9H0I9	943
TALDO1	TKT	P29401	943
TALDO1	TKTL1	P51854	943
TALDO1	PGD	P52209	847
TALDO1	RPE	Q96AT9	837
TALDO1	H6PD	O95479	811
TALDO1	G6PD	P11413	809
TALDO1	PGK1	P00558	780
TALDO1	TPI1	P00938	760
TALDO1	GPI	P06744	760
TALDO1	PGK2	P07205	754
TALDO1	XYLB	O75191	746
TALDO1	ENO1	P06733	746
TALDO1	RPEL1	Q2QD12	745

IntAct

47 interactions, top by confidence:

A	B	Type	Score
rep	ISG15	psi-mi:“MI:0914”(association)	0.910
TALDO1	HTT	psi-mi:“MI:0915”(physical association)	0.560
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
TERF2IP	TALDO1	psi-mi:“MI:0915”(physical association)	0.510
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
TERF1	TALDO1	psi-mi:“MI:0915”(physical association)	0.370
TERF2	TALDO1	psi-mi:“MI:0915”(physical association)	0.370
TALDO1	“SH	psi-mi:“MI:0915”(physical association)	0.370
CHD3	TALDO1	psi-mi:“MI:0915”(physical association)	0.370
TALDO1	ZHX1	psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TALDO1	PDE6D	psi-mi:“MI:0914”(association)	0.350
DENR	ATG13	psi-mi:“MI:0914”(association)	0.350
CAV1	PPM1G	psi-mi:“MI:0914”(association)	0.350
TRIM24	DDTL	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
MAP3K7	ACOT7	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
INPPL1	ACTN4	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (165): SPC24 (Affinity Capture-MS), CFDP1 (Affinity Capture-MS), ATG2B (Affinity Capture-MS), RNF40 (Affinity Capture-MS), PDE6D (Affinity Capture-MS), PJA1 (Affinity Capture-MS), TP73 (Affinity Capture-MS), PRKACB (Affinity Capture-MS), WDR45 (Affinity Capture-MS), PMF1 (Affinity Capture-MS), DENR (Affinity Capture-MS), ZNF655 (Affinity Capture-MS), AKR1A1 (Co-fractionation), PITPNB (Co-fractionation), PSMG4 (Co-fractionation)

ESM2 similar proteins: A0A075DVI9, A2BVI1, A2C0X8, A3PBP3, A8FSH3, A8H1G4, A9BEE2, B0TJA0, B0UV30, B1JL09, B1KIS4, B2K3L5, B3PDM9, B4F2V2, B8CSD3, B8D6Z9, B8D8P5, C4K4G2, J9MJK9, O84315, P15019, P37837, P51778, P53228, P57194, P58561, Q07Z25, Q0I1U0, Q255E4, Q31C15, Q3KM49, Q46GQ7, Q47WR3, Q54UP4, Q5L5I5, Q66ET5, Q6MAI4, Q7N8Z1, Q7V2G1, Q7VD64

Diamond homologs: A0A075DVI9, A0L002, A1JJD0, A1RMN6, A1S414, A3D1F5, A3MYD4, A3N794, A3QBW2, A4SK74, A4Y494, A5F028, A5UCY0, A5UIP9, A6VLW0, A6VYA4, A6WKC4, A7FME9, A7N1Z7, A8FSH3, A8H1G4, A9L4T6, A9R021, B0BRM0, B0TJA0, B0UV30, B1JL09, B1KIS4, B1YU93, B2JE74, B2K3L5, B2T236, B3GZQ2, B3PDM9, B3R1I4, B4F2V2, B4RX40, B5EUF3, B6ERE2, B8CSD3

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TALDO1	“down-regulates quantity”	“sedoheptulose 7-phosphate”	“chemical modification”
TALDO1	“down-regulates quantity”	“D-glyceraldehyde 3-phosphate(2-)”	“chemical modification”
TALDO1	“up-regulates quantity”	“β-D-fructose 6-phosphate”	“chemical modification”
TALDO1	“up-regulates quantity”	“D-erythrose 4-phosphate(2-)”	“chemical modification”
NFE2L2	“up-regulates quantity by expression”	TALDO1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Cellular Senescence	6	19.7×	2e-04
DNA Repair	5	11.7×	3e-03
SARS-CoV-2 Infection	5	9.6×	4e-03
Cellular responses to stress	7	6.1×	4e-03
Cellular responses to stimuli	7	5.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	8
Uncertain significance	110
Likely benign	91
Benign	7

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
1450849	NC_000011.9:g.(?747482)(747598_?)del	Pathogenic
162622	NM_006755.2(TALDO1):c.793del (p.Gln265fs)	Pathogenic
1967312	NM_006755.2(TALDO1):c.643_644del (p.Lys215fs)	Pathogenic
208617	NM_006755.2(TALDO1):c.516dup (p.Ala173fs)	Pathogenic
2578671	GRCh37/hg19 11p15.5(chr11:763344-764433)x0	Pathogenic
3040700	NM_006755.2(TALDO1):c.646_647del (p.Ser216fs)	Pathogenic
3244767	NC_000011.9:g.(?747482)(764845_?)del	Pathogenic
3244768	NC_000011.9:g.(?763324)(764453_?)del	Pathogenic
3609749	NM_006755.2(TALDO1):c.304C>T (p.Arg102Ter)	Pathogenic
3653626	NM_006755.2(TALDO1):c.49C>T (p.Gln17Ter)	Pathogenic
3679268	NM_006755.2(TALDO1):c.289A>T (p.Lys97Ter)	Pathogenic
381759	NM_006755.2(TALDO1):c.574C>T (p.Arg192Cys)	Pathogenic
4083502	GRCh37/hg19 11p15.5(chr11:763344-764433)x1	Pathogenic
4694555	NM_006755.2(TALDO1):c.699dup (p.Met234fs)	Pathogenic
625864	NM_006755.2(TALDO1):c.931G>T (p.Gly311Trp)	Pathogenic
812704	NM_006755.2(TALDO1):c.715C>G (p.Arg239Gly)	Pathogenic
1923526	NM_006755.2(TALDO1):c.97+1G>A	Likely pathogenic
2414536	NM_006755.2(TALDO1):c.836-1G>A	Likely pathogenic
2585189	NM_006755.2(TALDO1):c.695_696del (p.Ile232fs)	Likely pathogenic
2636699	NM_006755.2(TALDO1):c.931G>A (p.Gly311Arg)	Likely pathogenic
3702304	NM_006755.2(TALDO1):c.835+1G>A	Likely pathogenic
3780691	NM_006755.2(TALDO1):c.98-2A>G	Likely pathogenic
4376951	NM_006755.2(TALDO1):c.222-2A>G	Likely pathogenic
817009	NM_006755.2(TALDO1):c.750dup (p.Asp251Ter)	Likely pathogenic

SpliceAI

1277 predictions. Top by Δscore:

Variant	Effect	Δscore
11:755877:A:AG	acceptor_gain	1.0000
11:755878:G:GG	acceptor_gain	1.0000
11:755878:GCC:G	acceptor_gain	1.0000
11:755991:G:GT	donor_gain	1.0000
11:755998:GGCGG:G	donor_gain	1.0000
11:755999:GCGG:G	donor_gain	1.0000
11:755999:GCGGG:G	donor_gain	1.0000
11:756001:GG:G	donor_gain	1.0000
11:756002:GG:G	donor_gain	1.0000
11:756002:GGT:G	donor_loss	1.0000
11:756003:G:GG	donor_gain	1.0000
11:756004:T:A	donor_loss	1.0000
11:756005:GAGT:G	donor_loss	1.0000
11:758940:T:TA	acceptor_gain	1.0000
11:758943:A:AG	acceptor_gain	1.0000
11:758947:CAGG:C	acceptor_loss	1.0000
11:758948:A:AG	acceptor_gain	1.0000
11:758948:AGG:A	acceptor_loss	1.0000
11:758949:G:GG	acceptor_gain	1.0000
11:759053:GCAAG:G	donor_gain	1.0000
11:759058:G:GG	donor_gain	1.0000
11:759058:GTAAG:G	donor_loss	1.0000
11:760118:ACAG:A	acceptor_gain	1.0000
11:760119:C:G	acceptor_gain	1.0000
11:760119:CAGGC:C	acceptor_loss	1.0000
11:760120:A:AG	acceptor_gain	1.0000
11:760120:AG:A	acceptor_gain	1.0000
11:760120:AGG:A	acceptor_loss	1.0000
11:760121:G:GA	acceptor_gain	1.0000
11:760121:GG:G	acceptor_gain	1.0000

AlphaMissense

2207 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:763447:T:C	F189L	1.000
11:763449:T:A	F189L	1.000
11:763449:T:G	F189L	1.000
11:764395:T:C	F315L	1.000
11:764397:T:A	F315L	1.000
11:764397:T:G	F315L	1.000
11:747560:G:C	D27H	0.999
11:755916:C:A	N45K	0.999
11:755916:C:G	N45K	0.999
11:747562:C:A	D27E	0.998
11:747562:C:G	D27E	0.998
11:755914:A:G	N45D	0.998
11:763390:T:C	F170L	0.998
11:763392:C:A	F170L	0.998
11:763392:C:G	F170L	0.998
11:763807:T:A	V233D	0.998
11:763824:C:A	R239S	0.998
11:763825:G:C	R239P	0.998
11:764383:G:T	G311W	0.998
11:764384:G:A	G311E	0.998
11:764396:T:G	F315C	0.998
11:747561:A:G	D27G	0.997
11:747561:A:T	D27V	0.997
11:755924:T:C	L48P	0.997
11:760216:A:G	K142E	0.997
11:763377:C:A	N165K	0.997
11:763377:C:G	N165K	0.997
11:763447:T:A	F189I	0.997
11:763448:T:G	F189C	0.997
11:763454:G:A	G191E	0.997

dbSNP variants (sampled 300 via entrez): RS1000137162 (11:752233 C>G), RS1000287498 (11:748518 G>A,T), RS1000431695 (11:759767 C>T), RS1000487116 (11:748036 G>GC), RS1000807601 (11:764276 C>T), RS1000895296 (11:758879 A>T), RS1001251240 (11:759267 T>A), RS1001311476 (11:764143 C>T), RS1001338796 (11:748128 G>A), RS1001343198 (11:750413 A>G), RS1001537847 (11:749080 G>A), RS1001590167 (11:748830 C>T), RS1001699551 (11:755005 A>AAG), RS1001764016 (11:763931 C>T), RS1001846391 (11:760357 GC>G)

Disease associations

OMIM: gene MIM:602063 | disease phenotypes: MIM:606003, MIM:116200

GenCC curated gene-disease

Disease	Classification	Inheritance
transaldolase deficiency	Definitive	Autosomal recessive

Mondo (3): transaldolase deficiency (MONDO:0011624), microcephaly (MONDO:0001149), cataract (MONDO:0005129)

Orphanet (1): Transaldolase deficiency (Orphanet:101028)

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000056	Abnormal clitoris morphology
HP:0000077	Abnormality of the kidney
HP:0000154	Wide mouth
HP:0000233	Thin vermilion border
HP:0000260	Wide anterior fontanel
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000369	Low-set ears
HP:0000470	Short neck
HP:0000664	Synophrys
HP:0000969	Edema
HP:0001009	Telangiectasia
HP:0001263	Global developmental delay
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001410	Decreased liver function
HP:0001413	Micronodular cirrhosis
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001562	Oligohydramnios
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus
HP:0001655	Patent foramen ovale
HP:0001680	Coarctation of aorta
HP:0001744	Splenomegaly
HP:0001789	Hydrops fetalis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003141_2	Proteinuria and chronic kidney disease	9.000000e-06
GCST90013442_17	Keratoconus	1.000000e-26

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002386	Cataract	C11.510.245
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C563207	Transaldolase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066447 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.45	Kd	358.6	nM	CHEMBL5653589
6.45	ED50	358.6	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 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	2149539: Binding affinity to human TALDO1 incubated for 45 mins by Kinobead based pull down assay	kd	0.3586	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	6
bisphenol A	affects expression, decreases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Benzo(a)pyrene	increases expression	3
Cyclosporine	increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Cisplatin	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression, affects expression	2
Cadmium Chloride	increases expression	2
beta-Naphthoflavone	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
chloroacetaldehyde	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
lead acetate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction, increases reaction	1
sulforaphane	increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
benzo(e)pyrene	decreases methylation	1
cupric chloride	increases expression	1
hydroquinone	affects expression	1
microcystin RR	decreases expression	1
macrosphelide A	affects binding	1
K 7174	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases 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
CHEMBL5652581	Binding	Binding affinity to human TALDO1 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_B3J0	Abcam HEK293T TALDO1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00273221	PHASE4	UNKNOWN	Combined Phacotube vs Phacotrabeculectomy:A Randomized Controlled Trial
NCT00312299	PHASE4	COMPLETED	Posterior Capsule Opacification Study
NCT00345046	PHASE4	COMPLETED	A Comparison of Three Different Formulations of Prednisolone Acetate 1%
NCT00347243	PHASE4	COMPLETED	Wavefront Analisys and Contrast Sensitivity of Spherical and Aspherical Intraocular Lenses
NCT00347503	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients
NCT00348244	PHASE4	COMPLETED	Ketorolac vs. Steroid in the Prevention of CME
NCT00348270	PHASE4	COMPLETED	Comparison of the Quality of Vision Provided by AMO Tecnis Z9000 and Alcon Laboratories MA60 Acrysof Posterior Chamber Intraocular Lenses
NCT00348582	PHASE4	COMPLETED	Acular LS vs. Nevanac in Post op Inflammation Following Cataract Surgery
NCT00348621	PHASE4	COMPLETED	A Study of Interventions to Reduce Disability From Visual Loss in Nursing Home Residents
NCT00349583	PHASE4	COMPLETED	Efficacy of Topical Cyclosporine Versus Tears for Improving Visual Outcomes Following Multifocal IOL Implantation
NCT00355446	PHASE4	COMPLETED	Bioavailability of Bimatoprost Ophthalmic Solution in Human Aqueous.
NCT00386438	PHASE4	COMPLETED	Efficacy of Honan Balloon in Intraocular Pressure Reduction Before Phacoemulsification
NCT00392275	PHASE4	COMPLETED	Penetrance of Third Generation Fluoroquinolones in Eyes With Functioning Filtering Blebs
NCT00428363	PHASE4	COMPLETED	Effect of Optic Edge Design in a Silicone Intraocular Lens on Posterior Capsule Opacification
NCT00449267	PHASE4	COMPLETED	Aurolab Hydrophobic Foldable Intraocular Lens Study
NCT00459303	PHASE4	COMPLETED	Comparison of Functional Vision Provided by AMO Tecnis Z9000 and Alcon SA60AT Acrysof
NCT00469690	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients: Trough Drug Effects
NCT00576485	PHASE4	COMPLETED	Spherical Aberration and Contrast Sensitivity in IOLs
NCT00612729	PHASE4	COMPLETED	Light Filters in Intraocular Lenses (IOLs) and Its Influence on Colour and Contrast Vision.
NCT00612781	PHASE4	COMPLETED	Yellow Versus White Study
NCT00630019	PHASE4	COMPLETED	Ocular Tissue Levels of 1.5% Levofloxacin Ophthalmic Solution Compared to an Active Comparator
NCT00673803	PHASE4	COMPLETED	Influence of Two Different Preloaded Intraocular Lens (IOLs) on Posterior Capsule Opacification
NCT00684138	PHASE4	COMPLETED	ACRYSOF® ReSTOR® Aspheric +3.0 D Add Power Intraocular Lens (IOL)
NCT00698724	PHASE4	COMPLETED	Comparing Optical Coherence Tomography (OCT) and Visual Acuity Outcomes in Subjects Undergoing Cataract Surgery, Who Receive Xibrom Ophthalmic Solution and Standard Presurgical Care vs. Xibrom Ophthalmic Solution Plus Prednisolone Acetate 1% and Standard Presurgical Care
NCT00710905	PHASE4	TERMINATED	Visual Function With Contralateral AcrySof® ReSTOR® Aspheric SN6AD1 and SN6AD3
NCT00710931	PHASE4	COMPLETED	Visual Function With Bilateral AcrySof® ReSTOR® Aspheric SN6AD1
NCT00711347	PHASE4	COMPLETED	Intraoperative Floppy Iris Syndrome
NCT00712244	PHASE4	COMPLETED	DisCoVisc Versus DuoVisc, Healon5 and AmVisc Plus
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00719732	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof ReSTOR Aspheric +3
NCT00721253	PHASE4	COMPLETED	Visual Outcomes of Subjects Bilaterally Implanted With ReSTOR Aspheric +4 vs. Tecnis or Acri.LISA
NCT00731640	PHASE4	COMPLETED	Contralateral ReSTOR / Monofocal or Phakic Eye
NCT00732030	PHASE4	COMPLETED	Low Cylinder Toric
NCT00758199	PHASE4	COMPLETED	Determination of Optimum Duration of Treatment With Bromfenac (Xibrom) Eyedrops Following Cataract Surgery
NCT00760058	PHASE4	WITHDRAWN	Visual Outcome and Visual Quality After Bilateral Implantation of the AcrySof® IQ IOL Compared to MI60® and Tecnis® IOL
NCT00760487	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof® Toric Natural Intraocular Lens
NCT00761488	PHASE4	WITHDRAWN	Recommendations for Monitoring Clinical Experience Following Implantation of the AcrySof® Toric
NCT00763360	PHASE4	COMPLETED	To Compare the Ability of DiscoVisc® OVD to Protect the Corneal Endothelium and Maintain Anterior Chamber Space With Healon® and Amvisc® PLUS During Cataract Surgery.
NCT00786370	PHASE4	COMPLETED	Dexmedetomidine vs. Propofol for Cataract Surgery
NCT00786565	PHASE4	COMPLETED	Clinical Evaluation of a New Aspheric Intraocular Lens.