HACE1

Highest pathogenic variant AF is 0.000018720359

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000262903

Coding exons

24

Length

131827

Individuals with no LoFs

125701

Homozygous LoFs

0

Heterozygous LoFs

47

Defined

125748

p

0.000187

Function

FUNCTION: E3 ubiquitin-protein ligase involved in Golgi membrane fusion and regulation of small GTPases. Acts as a regulator of Golgi membrane dynamics during the cell cycle: recruited to Golgi membrane by Rab proteins and regulates postmitotic Golgi membrane fusion. Acts by mediating ubiquitination during mitotic Golgi disassembly, ubiquitination serving as a signal for Golgi reassembly later, after cell division. Specifically interacts with GTP-bound RAC1, mediating ubiquitination and subsequent degradation of active RAC1, thereby playing a role in host defense against pathogens. May also act as a transcription regulator via its interaction with RARB. {ECO:0000269|PubMed:15254018, ECO:0000269|PubMed:21988917, ECO:0000269|PubMed:22036506}.;

Disease

DISEASE: Note=Defects in HACE1 are a cause of Wilms tumor (WT). WT is a pediatric malignancy of kidney and one of the most common solid cancers in childhood. HACE1 is epigenetically down-regulated in sporadic Wilms tumor. Moreover, a t(5;6)(q21;q21) translocation that truncates HACE1 has been found in a child with bilateral, young-onset Wilms tumor (PubMed:19948536). {ECO:0000269|PubMed:17694067, ECO:0000269|PubMed:19948536}.; DISEASE: Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) [MIM:616756]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPPRS is an autosomal recessive neurodevelopmental disorder manifesting in infancy. Affected individuals show hypotonia and psychomotor retardation. Most develop seizures. {ECO:0000269|PubMed:26424145, ECO:0000269|PubMed:26437029}. Note=The disease is caused by mutations affecting the gene represented in this entry.;