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Autosomal recessive variants in CLIP1 are implicated in non-syndromic intellectual disability. In a consanguineous Iranian family, autozygosity mapping yielded an ID locus at Chr. 12q24 (LOD 3.7 PMID:24569606), and exome sequencing identified a homozygous nonsense variant, c.3061C>T (p.Gln1021Ter), segregating with disease. Patient lymphoblastoid and fibroblast lines lacked CLIP1 transcript and protein, and CLIP170 plus-end microtubule staining was absent in mutant cells (PMID:24569606).
These limited genetic findings and consistent cellular phenotypes support a ClinGen Limited level of evidence for CLIP1 in autosomal recessive intellectual disability. Additional unrelated families and in vivo model studies would strengthen the association. Key Take-home: CLIP1 loss-of-function variants cause autosomal recessive intellectual disability and warrant inclusion of CLIP1 in diagnostic panels.
Gene–Disease AssociationLimitedSingle consanguineous family with homozygous nonsense variant (LOD 3.7); loss of transcript and protein in patient cells Genetic EvidenceLimitedHomozygous nonsense variant in CLIP1 segregating with disease in one family (LOD 3.7) Functional EvidenceModeratePatient cell lines lack CLIP1 transcript and protein; loss of MT plus-end staining supports loss-of-function mechanism |