ITPA

Chr 20AR

inosine triphosphatase

Also known as: C20orf37, DEE35, HLC14-06-P, ITPase, My049, NTPase, dJ794I6.3

The encoded protein functions as an inosine triphosphate pyrophosphohydrolase that hydrolyzes inosine triphosphate and deoxyinosine triphosphate to monophosphate nucleotides and diphosphate in the cytoplasm. Mutations cause autosomal recessive inosine triphosphatase deficiency, which leads to ITP accumulation in red blood cells, and developmental and epileptic encephalopathy 35. The pathogenic mechanism appears to involve dominant-negative effects of mutant proteins.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 1.352 OMIM phenotypes
Clinical SummaryITPA
🧬
Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.35LOEUF
pLI 0.000
Z-score 0.58
OE 0.84 (0.531.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.12Z-score
OE missense 0.97 (0.831.13)
111 obs / 114.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.84 (0.531.35)
00.351.4
Missense OE0.97 (0.831.13)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 12 / 14.4Missense obs/exp: 111 / 114.7Syn Z: -0.45
DN
0.6743th %ile
GOF
0.3689th %ile
LOF
0.3066th %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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ITPA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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