This report describes spastic paraplegia 61 (SPG61), which is a subtype of spastic paraplegia; SPG61 is inherited as an autosomal recessive. The human gene implicated in this disease is ARL6IP1 (ADP ribosylation factor-like GTPase 6-interacting protein 1) which encodes a transmembrane protein that is predominantly localized to intracytoplasmic membranes. There is a single Drosophila ortholog, Arl6IP1, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human ARL6IP1 gene has not been introduced into flies.
Neuronal knockdown of Dmel\Arl6IP1 effected by RNAi results in a progressive locomotor deficit; disruption of the smooth ER and mitochondria at the distal ends of motor neurons is observed.
[updated Mar. 2017 by FlyBase; FBrf0222196]
The hereditary spastic paraplegias (SPG, HSP) are a large group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity and weakness. SPG is classified by mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and whether the primary symptoms occur in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'). [from MIM:182600; 15.06.29]
[SPASTIC PARAPLEGIA 61, AUTOSOMAL RECESSIVE; SPG61](https://omim.org/entry/615685)
[ADP-RIBOSYLATION FACTOR-LIKE GTPase 6-INTERACTING PROTEIN 1; ARL6IP1](https://omim.org/entry/607669)
See general description of spastic paraplegia above. Spastic paraplegia 61 (SPG61) is a complicated form of spastic paraplegia with sensory and motor polyneuropathy. [from MIM:615685; 2017.03.03]
There is evidence that spastic paraplegia 61 (SPG61) is caused by homozygous mutation in the ARL6IP1 gene (autosomal recessive); one such family has been reported. [from MIM:615685; 2017.03.03]
ARL6IP1 belongs to the ARL6ip family and encodes a transmembrane protein that is predominantly localized to intracytoplasmic membranes. It is highly expressed in early myeloid progenitor cells and thought to be involved in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation. [Gene Cards, ARL6IP1l; 2017.03.03]
One to one (1 human to 1 Drosophila).
High-scoring ortholog of human ARL6IP1 (1 Drosophila to 1 human). Dmel\Arl6IP1 shares 29% identity and 53% similarity with human ARL6IP1.
