Transaldolase deficiency

Summary

Transaldolase deficiency (MONDO:0011624) is a disease caused by TALDO1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TALDO1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 54
• Phenotypes (HPO): 18

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		23	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0001394	Cirrhosis	Very frequent (80-99%)
HP:0001433	Hepatosplenomegaly	Very frequent (80-99%)
HP:0001873	Thrombocytopenia	Very frequent (80-99%)
HP:0001903	Anemia	Very frequent (80-99%)
HP:0010903	Abnormality of glutamine metabolism	Very frequent (80-99%)
HP:0012202	Increased serum bile acid concentration	Very frequent (80-99%)
HP:0000056	Abnormality of the clitoris	Frequent (30-79%)
HP:0000077	Abnormality of the kidney	Frequent (30-79%)
HP:0000969	Edema	Frequent (30-79%)
HP:0001009	Telangiectasia	Frequent (30-79%)
HP:0001789	Hydrops fetalis	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0100678	Premature skin wrinkling	Frequent (30-79%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001680	Coarctation of aorta	Occasional (5-29%)
HP:0002795	Abnormal respiratory system physiology	Occasional (5-29%)
HP:0200128	Biventricular hypertrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	transaldolase deficiency
Mondo ID	MONDO:0011624
MeSH	C563207
OMIM	606003
Orphanet	101028
ICD-11	424536994
SNOMED CT	124252008
UMLS	C1291329
MedGen	224855
GARD	0010445
Is cancer (heuristic)	no

Also known as: TALDO deficiency · transaldolase deficiency

Data availability: 54 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorders of pentose/polyol metabolism › inborn disorder of pentose phosphate metabolism › transaldolase deficiency

Related subtypes (5): pentosuria, anemia, nonspherocytic hemolytic, due to G6PD deficiency, ribose-5-P isomerase deficiency, transketolase deficiency, isolated sedoheptulokinase deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

54 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 10 pathogenic, 7 conflicting classifications of pathogenicity, 3 likely pathogenic, 2 benign, 1 benign/likely benign, 1 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
7562	NM_006755.2(TALDO1):c.512_514del (p.Ser171del)	LOC126861110	Pathogenic	no assertion criteria provided
974772	NM_006755.2(TALDO1):c.669C>G (p.Tyr223Ter)	LOC126861110	Pathogenic	no assertion criteria provided
162622	NM_006755.2(TALDO1):c.793del (p.Gln265fs)	TALDO1	Pathogenic	criteria provided, multiple submitters, no conflicts
1967312	NM_006755.2(TALDO1):c.643_644del (p.Lys215fs)	TALDO1	Pathogenic	criteria provided, multiple submitters, no conflicts
208617	NM_006755.2(TALDO1):c.516dup (p.Ala173fs)	TALDO1	Pathogenic	criteria provided, single submitter
3040700	NM_006755.2(TALDO1):c.646_647del (p.Ser216fs)	TALDO1	Pathogenic	criteria provided, single submitter
381759	NM_006755.2(TALDO1):c.574C>T (p.Arg192Cys)	TALDO1	Pathogenic	criteria provided, multiple submitters, no conflicts
4083502	GRCh37/hg19 11p15.5(chr11:763344-764433)x1	TALDO1	Pathogenic	criteria provided, single submitter
420180	NM_006755.2(TALDO1):c.575G>A (p.Arg192His)	TALDO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
625864	NM_006755.2(TALDO1):c.931G>T (p.Gly311Trp)	TALDO1	Pathogenic	no assertion criteria provided
812704	NM_006755.2(TALDO1):c.715C>G (p.Arg239Gly)	TALDO1	Pathogenic	no assertion criteria provided
2575047	NM_006755.2(TALDO1):c.512C>T (p.Ser171Phe)	LOC126861110	Likely pathogenic	no assertion criteria provided
2585189	NM_006755.2(TALDO1):c.695_696del (p.Ile232fs)	TALDO1	Likely pathogenic	criteria provided, single submitter
3780691	NM_006755.2(TALDO1):c.98-2A>G	TALDO1	Likely pathogenic	criteria provided, single submitter
883972	NM_006755.2(TALDO1):c.462-4G>A	LOC126861110	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306128	NM_006755.2(TALDO1):c.197T>C (p.Ile66Thr)	TALDO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306131	NM_006755.2(TALDO1):c.461+14C>T	TALDO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306133	NM_006755.2(TALDO1):c.476A>G (p.Gln159Arg)	TALDO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
730798	NM_006755.2(TALDO1):c.930C>T (p.Asp310=)	TALDO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
747285	NM_006755.2(TALDO1):c.36G>A (p.Glu12=)	TALDO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
883045	NM_006755.2(TALDO1):c.-6C>T	TALDO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306135	NM_006755.2(TALDO1):c.662A>G (p.Tyr221Cys)	LOC126861110	Uncertain significance	criteria provided, multiple submitters, no conflicts
800779	NM_006755.2(TALDO1):c.604G>A (p.Asp202Asn)	LOC126861110	Uncertain significance	criteria provided, single submitter
1028548	NM_006755.2(TALDO1):c.888G>A (p.Trp296Ter)	TALDO1	Uncertain significance	criteria provided, single submitter
1028549	NM_006755.2(TALDO1):c.982G>A (p.Glu328Lys)	TALDO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034304	NM_006755.2(TALDO1):c.330-10_330delinsAGA	TALDO1	Uncertain significance	criteria provided, single submitter
1398818	NM_006755.2(TALDO1):c.871G>A (p.Glu291Lys)	TALDO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436937	NM_006755.2(TALDO1):c.568G>T (p.Val190Phe)	TALDO1	Uncertain significance	criteria provided, single submitter
306087	NM_006755.2(TALDO1):c.48C>T (p.Asp16=)	TALDO1	Uncertain significance	criteria provided, single submitter
306088	NM_006755.2(TALDO1):c.68C>G (p.Thr23Ser)	TALDO1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TALDO1	Definitive	Autosomal recessive	transaldolase deficiency	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TALDO1	Orphanet:101028	Transaldolase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TALDO1	HGNC:11559	ENSG00000177156	P37837	Transaldolase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TALDO1	Transaldolase	Catalyzes the rate-limiting step of the non-oxidative phase in the pentose phosphate pathway.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TALDO1	Other/Unknown	no		TAL/FSA, Transaldolase_1, Aldolase_TIM

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood	1
gingival epithelium	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TALDO1	294	ubiquitous	marker	trabecular bone tissue, blood, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TALDO1	3,738

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TALDO1	P37837	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TALDO1 deficiency: failed conversion of SH7P, GA3P to Fru(6)P, E4P	1	11420.0×	0.001	TALDO1
TALDO1 deficiency: failed conversion of Fru(6)P, E4P to SH7P, GA3P	1	11420.0×	0.001	TALDO1
Insulin effects increased synthesis of Xylulose-5-Phosphate	1	5710.0×	0.001	TALDO1
Pentose phosphate pathway disease	1	5710.0×	0.001	TALDO1
NFE2L2 regulates pentose phosphate pathway genes	1	1427.5×	0.003	TALDO1
Pentose phosphate pathway	1	951.7×	0.004	TALDO1
Diseases of carbohydrate metabolism	1	815.7×	0.004	TALDO1
Interleukin-12 family signaling	1	475.8×	0.006	TALDO1
Interleukin-12 signaling	1	407.9×	0.006	TALDO1
Nuclear events mediated by NFE2L2	1	335.9×	0.007	TALDO1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	300.5×	0.007	TALDO1
Integration of energy metabolism	1	175.7×	0.011	TALDO1
Cellular response to chemical stress	1	142.8×	0.012	TALDO1
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.013	TALDO1
KEAP1-NFE2L2 pathway	1	120.2×	0.013	TALDO1
Diseases of metabolism	1	80.4×	0.018	TALDO1
Signaling by Interleukins	1	64.2×	0.021	TALDO1
Cytokine Signaling in Immune system	1	40.8×	0.031	TALDO1
Cellular responses to stress	1	36.8×	0.033	TALDO1
Cellular responses to stimuli	1	31.5×	0.037	TALDO1
Disease	1	13.1×	0.081	TALDO1
Immune System	1	13.0×	0.081	TALDO1
Metabolism	1	11.6×	0.086	TALDO1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pentose-phosphate shunt, non-oxidative branch	1	2808.7×	0.001	TALDO1
fructose 6-phosphate metabolic process	1	1123.5×	0.001	TALDO1
carbohydrate metabolic process	1	135.9×	0.007	TALDO1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TALDO1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TALDO1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TALDO1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TALDO1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.