TKTL2

Chr 4

transketolase like 2

NCBI Gene: 84076 ENSG00000151005 UniProt: Q9H0I9

TKTL2 encodes a protein with transketolase activity that plays an essential role in total cellular transketolase activity and cell proliferation. Mutations cause autosomal recessive intellectual disability with seizures and macrocephaly. The gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

Predicted to enable thiamine pyrophosphate binding activity and transketolase activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.17

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.17LOEUF

pLI 0.000

Z-score 1.02

OE 0.74 (0.48–1.17)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.05Z-score

OE missense 0.99 (0.91–1.08)

374 obs / 376.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.48–1.17)

0≤0.351.4

Missense OE?0.99 (0.91–1.08)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 13 / 17.6Missense obs/exp: 374 / 376.5Syn Z: 1.57

Background carrier burden — how many people carry a rare variant somewhere in TKTL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 49

885 rare PASS variants

Rare truncating (LoF)

1 in 530

92 rare PASS variants

Rare synonymous (reference)

1 in 110

276 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TKTL2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 84	1 in 540
South Asian	~43k	1 in 76	1 in 1,300
Remaining (unassigned)	~30k	1 in 48	1 in 810
European (Finnish)	~27k	1 in 370	1 in 5,300
Admixed American	~22k	1 in 52	1 in 980
African / African American	~21k	1 in 58	1 in 290
East Asian	~20k	1 in 56	1 in 960
Ashkenazi Jewish	~13k	1 in 250	none seen
Middle Eastern	~2,884	1 in 72	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓