ITPRIPL2

Chr 16

ITPRIP like 2

Also known as: D1C

NCBI Gene: 162073 ENSG00000205730 UniProt: Q3MIP1

The ITPRIPL2 protein is predicted to be located in cellular membranes, though its specific function remains unclear. Mutations in this gene cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability and early-onset seizures. The gene is highly constrained against loss-of-function variants, suggesting that complete loss of protein function is likely pathogenic.

ResearchSummary from RefSeq

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.05

Clinical Summary— ITPRIPL2

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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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ClinVar Variants

69 VUS of 77 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.42

OE 0.58 (0.34–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.59Z-score

OE missense 0.76 (0.69–0.84)

264 obs / 347.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.34–1.05)

0≤0.351.4

Missense OE?0.76 (0.69–0.84)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 8 / 13.7Missense obs/exp: 264 / 347.3Syn Z: 1.62

ClinVar Variant Classifications

77 submitted variants in ClinVar

ClinVar

Classification Summary

VUS69

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	69	0	69
Likely Benign	0	1	1
Benign	0	0	0
Total	69	1	70

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap ITPRIPL2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →