CRIPT

Chr 2AR

CXXC repeat containing interactor of PDZ3 domain

Also known as: HSPC139, RTS3, SSMDF

NCBI Gene: 9419 ENSG00000119878 UniProt: Q9P021 OMIM: 604594

CRIPT encodes a protein that anchors DLG4 in excitatory synapses and is involved in splicing of U12-type introns in pre-mRNAs as a component of the minor spliceosome. Autosomal recessive mutations cause Rothmund-Thomson syndrome type 3, characterized by short stature, microcephaly, and distinctive facial features. The gene shows tolerance to loss-of-function variants (pLI 0.001, LOEUF 1.58), suggesting the pathogenic variants may have residual function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that binds to the PDZ3 peptide recognition domain. The encoded protein may modulates protein interactions with the cytoskeleton. A mutation in this gene resulted in short stature with microcephaly and distinctive facies. [provided by RefSeq, Jun 2014]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.581 OMIM phenotype

Clinical Summary— CRIPT

⚡

Population Constraint (gnomAD)

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

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.58LOEUF

pLI 0.001

Z-score 0.52

OE 0.78 (0.41–1.58)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.39Z-score

OE missense 1.16 (0.94–1.44)

57 obs / 49.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.78 (0.41–1.58)

0≤0.351.4

Missense OE?1.16 (0.94–1.44)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 5 / 6.4Missense obs/exp: 57 / 49.2Syn Z: 0.40

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongCRIPT-related short stature, microcephaly, poikiloderma and skeletal abnormalities (Rothmund Thomson like)OTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6549th %ile

GOF

0.6639th %ile

LOF

0.4234th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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