Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: ATRIP

Green List (high evidence)

Comment on list classification: There are now 3 unrelated probands reported in literature with primary immunodeficiency (neutropenia, lymphopenia, recurrent infections), habrouring homozygous variants in ATRIP. Hence, ATRIP can be promoted to Green on this panel.

Created: 27 Oct 2026, 11:35 a.m. | Last Modified: 27 Oct 2026, 11:35 a.m.

Panel Version: 9.111

PMID: 40029331 Duthoo et al., 2025
Study identified homozygous splice ATRIP variants in two patients of independent ancestry with microcephaly, primordial dwarfism, and recurrent infections.
Patient F1Pt: female with severe microcephaly, developmental delay, dysmorphic features, growth retardation, grossly normal skeletal development, and a mild ID. She had recurrent respiratory tract infections. Lab investigations showed lymphopenia and intermittent neutropenia. WES revealed a homozygous c.829+5G>T variant in ATRIP. Based on figure S1, severity of microcephaly was close to -6 SD below mean for OFC.
Second patient, F46.1, was previously reported in PMID: 35568357.

PMID: 35568357 Masih et al., 2022
Report of 87 Indian families with microcephaly.
P F46.1 - 5yo male - presented with microcephaly OFC 38cm (Z score − 9.4), moderate ID/DD, febrile seizures, facial dysmorphism, dry skin, recurrent respiratory tract infections, clubbing of digits, short stature, speech delay. CT was normal. He was diagnosed with Seckel syndrome. Proband harboured a homozygous ATRIP variant: c.829+2T>G. Method: exome seq.

PMID: 23144622 Ogi et al., 2012
Report of a patient, born of consanguineous Gujarati-Indian parents, with Seckel syndrome. Proband harboured comp het ATRIP variants: c.2278C-T, p.Arg760Ter and a splicing defect c.248-14A<G. Parents confirmed het for a variant each and unaffected. The patient had severe microcephaly (-10 SD), micrognathia, dental crowding, small earlobes, delayed bone age, and symmetric dwarfism.
Reappraisal of patient CV1720’s clinical status in PMID: 40029331 revealed a phenotype of late-onset lymphopenia and intermittent neutropenia.

ATRIP is not yet associated with a disease entity in OMIM. ClinGen and G2P only list AD associations with breast cancer susceptibility. Resources accessed 27th Oct 2026.
Sources: Literature

Created: 27 Oct 2026, 11:34 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Seckel syndrome, MONDO:0019342; Recurrent infections, HP:0002719

Publications

• 23144622
• 35568357
• 40029331