ITPRIPL1

Chr 2

ITPRIP like 1

Also known as: D1B, KIAA1754L

NCBI Gene: 150771 ENSG00000198885 UniProt: Q6GPH6 OMIM: 620821

The protein functions as a ligand of CD3E that inhibits T cell receptor signaling by preventing CD3E-ZAP70 interaction and downstream ERK-NFkB cascade activation. Mutations cause autosomal recessive severe combined immunodeficiency and autosomal recessive T cell immunodeficiency. The gene shows extremely low constraint against loss-of-function variants, suggesting tolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

Enables receptor ligand activity. Involved in negative regulation of T cell receptor signaling pathway. Located in membrane. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.37

Clinical Summary— ITPRIPL1

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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

88 VUS of 96 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.37LOEUF

pLI 0.000

Z-score 0.39

OE 0.90 (0.61–1.37)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.53Z-score

OE missense 0.92 (0.83–1.01)

298 obs / 324.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.90 (0.61–1.37)

0≤0.351.4

Missense OE?0.92 (0.83–1.01)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 16 / 17.8Missense obs/exp: 298 / 324.7Syn Z: 1.73

ClinVar Variant Classifications

96 submitted variants in ClinVar

ClinVar

Classification Summary

VUS88

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	88	88
Likely Benign	2	2
Benign	0	0
Total	90	90

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap ITPRIPL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →