TALDO1

protein-coding

transaldolase 1

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006755.2

Inheritance

ClinVar variants

P:29U:128B:78

Top phenotype

Transaldolase deficiency

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr11:747,415-765,012

External References & Databases

Ensembl (ENSG00000177156)

Transcript & Mutation Effects

hg38 • Region Span ~17.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

transaldolase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011624

Submitter: Orphanet

transaldolase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011624

Submitter: G2P

transaldolase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011624

Submitter: PanelApp Australia

transaldolase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011624

Submitter: Labcorp Genetics (formerly Invitae)

transaldolase deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011624

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Transaldolase deficiencyAR

Manifestation: Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Renal

Intervention: Biochemical; Pharmacogenomic

Rationale: The use of N--acetylcysteine therapy has been reported as beneficial related to at least laboratory-based parameters; Studies have suggested that individuals may be sensitive to acetaminophen therapy, and that this medication should be avoided due to the risk of toxicity

Refs: 11283793; 15877206; 17095351; 19401148; 21119539; 23315216; 27130472; 29923087

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TALDO1 variants in ClinVar

9 Conditions Cataloged

not providedTotal: 218

Inborn genetic diseasesTotal: 58

Deficiency of transaldolaseTotal: 50

TALDO1-related disorderTotal: 41

CataractTotal: 1

not specifiedTotal: 1

MicrocephalyTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006755.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	69 clinvar	2 clinvar	80
missense	3 clinvar	6 clinvar	110 clinvar	6 clinvar	1 clinvar	126
nonsense	4 clinvar	2 clinvar	2 clinvar			8
start loss			1 clinvar			1
frameshift	5 clinvar	4 clinvar	2 clinvar			11
splice donor/acceptor (+/-2bp)		5 clinvar	4 clinvar			9
Total	12	17	128	75	3	235

Highest pathogenic variant AF is 0.000042766722

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006755.2	RefSeq	NP_006746.1	8	MANE Select
ENST00000319006.8	Ensembl	ENSP00000321259.3	8	MANE Select
ENST00000528070.5	Ensembl	ENSP00000435042.1	2	Standard
ENST00000528097.5	Ensembl	ENSP00000437098.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pentose phosphate pathway - Homo sapiens (human)
Warburg Effect
Pentose Phosphate Pathway
Glucose-6-phosphate dehydrogenase deficiency
Ribose-5-phosphate isomerase deficiency

Biological Process

carbohydrate metabolic process
xylulose biosynthetic process
fructose 6-phosphate metabolic process
pentose-phosphate shunt
pentose-phosphate shunt, non-oxidative branch

Molecular Function

sedoheptulose-7-phosphate:D-glyceraldehyde-3-phosphate glyceronetransferase activity
protein binding
monosaccharide binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000319006
Coding exons: 8
Length: 17696
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125748
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.13	239	195	1.23	0.0000124	2194
Missense (PolyPhen)		77	67.707	1.1373		836
Synonymous	-0.957	93	82.0	1.13	0.00000578	648
Loss of Function	1.22	11	16.3	0.673	8.94e-7	197

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transaldolase is important for the balance of metabolites in the pentose-phosphate pathway.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:11283793}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.459

Intolerance Scores

LoFtool: 0.165
RVIS EVS: -0.73
RVIS percentile EVS: 14.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.979

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium