DYNC2I1

Phenotypes

Mouse phenotype:

abnormal stomach morphology, enlarged uriry bladder, embryonic growth retardation, preweaning lethality, complete penetrance, abnormal embryo size, pretal lethality prior to heart atrial septation, embryonic lethality prior to tooth bud stage

Human ciliopathy phenotype:

Short-rib thoracic dysplasia 8 with or without polydactyly (SRTD8, OMIM 615503): short ribs, narrow thorax, short long bones, polydactyly, with possible renal cysts and retinal involvement. Phenotypic spectrum from severe short-rib polydactyly syndromes (often perinatally lethal) to milder Jeune asphyxiating thoracic dystrophy. Biallelic WDR60 variants also reported in siblings with retinal degeneration and polydactyly lacking other skeletal features.

Ciliopathy associations

• Retinal Dystrophy/Degeneration
• Short-Rib Thoracic Dysplasia

References: PMID:23910462, PMID:25492405, PMID:26874042, PMID:29271569

Subcellular localization

basal body, centrosome, cilia

References: PMID:23910462, PMID:41005307

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Transcription regulation

Function

WD-repeat intermediate-chain subunit of the cytoplasmic dynein-2 motor complex (also known as DYNC2I1) that drives retrograde intraflagellar transport along the ciliary axoneme. Required for ciliary cargo retrieval, Hedgehog signal transduction, and skeletal patterning. Biallelic loss-of-function variants disrupt retrograde IFT and produce skeletal ciliopathy phenotypes (McInerney-Leo et al. 2013, PMID 23910462).