GATD3

Chr 21

glutamine amidotransferase class 1 domain containing 3

Also known as: C21orf33, ES1, GATD3A, GATD3B, GT335, HES1, KNPH, KNPI

NCBI Gene: 8209 ENSG00000160221 UniProt: P0DPI2 OMIM: 601659

GATD3 encodes a mitochondrial protein belonging to the DJ-1/PfpI gene family, though its specific function remains unclear. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene is not highly constrained against loss-of-function variants, consistent with recessive inheritance.

OMIM ResearchSummary from RefSeq

This gene encodes a potential mitochondrial protein that is a member of the DJ-1/PfpI gene family. This protein is overexpressed in fetal Down syndrome brain. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.38

Clinical Summary— GATD3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.38LOEUF

pLI 0.000

Z-score 0.70

OE 0.76 (0.45–1.38)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.70Z-score

OE missense 1.15 (1.02–1.30)

193 obs / 167.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.76 (0.45–1.38)

0≤0.351.4

Missense OE?1.15 (1.02–1.30)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 8 / 10.5Missense obs/exp: 193 / 167.5Syn Z: 0.85

This gene — mechanism propensity

0.7228th %ile

GOF

0.5759th %ile

LOF

0.3551th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.