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UBQLN1 encodes ubiquilin 1, a ubiquitin-like adaptor involved in proteostasis. A single de novo 2.6 Mb interstitial deletion on 9q21.32–q21.33 encompassing UBQLN1 and 11 other genes was identified in an infant presenting with intellectual disability and multiple congenital anomalies (PMID:24501764). Parental array CGH was negative, supporting a de novo haploinsufficiency mechanism.
Genetic evidence is limited: only one proband with a heterozygous deletion including UBQLN1 has been reported, with no additional unrelated cases or segregation data (PMID:24501764). No sequence‐level variants in UBQLN1 have been directly linked to intellectual disability to date.
Functional data are also limited. Prediction algorithms and preliminary experimental evidence from the deletion study suggest that UBQLN1 is dosage-sensitive and likely haploinsufficient, but no UBQLN1-specific assays in neurodevelopmental contexts have been performed (PMID:24501764).
No conflicting or refuting reports for UBQLN1 in intellectual disability are available. Additional cases and functional characterization of UBQLN1 loss-of-function are needed to clarify its role in neurodevelopment.
Key Take-home: Current evidence for UBQLN1 in intellectual disability is limited to a single de novo deletion; clinical testing should interpret UBQLN1 copy-loss cautiously and in the context of additional gene findings.
Gene–Disease AssociationLimitedSingle de novo 2.6 Mb deletion including UBQLN1 in one proband with intellectual disability and congenital anomalies (PMID:24501764). Genetic EvidenceLimitedOne proband with heterozygous UBQLN1-containing deletion; no recurrence or segregation (PMID:24501764). Functional EvidenceLimitedPrediction algorithms and preliminary haploinsufficiency data support loss-of-function mechanism (PMID:24501764). |