HHAT G287V doesn't palmitoylate Hh-Np

Stable Identifier
R-HSA-5483229
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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A G287V loss-of-function mutation in HHAT was identified in a rare case of Syndromic 46, XY Disorder of Sex Development, which results in testis dysgenesis. The mutation does not affect the stability, localization or expression level of the HHAT when expressed from a plasmid in COS-1 cells, but the mutant protein is unable to palmitoylate SHH or DHH in an in vitro assay and expression of the HHAT loss-of-function gene in mice recapitulates the phenotypes seen in the human patient (Callier et al, 2014). These findings support a role for DHH signaling in testis development, consistent with earlier reports (Umehara et al, 2000; Canto et al, 2004; Canto et al, 2005; Das et al, 2011).

Literature References
PubMed ID Title Journal Year
15356051 Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis

Canto, P, Söderlund, D, Reyes, E, Méndez, JP

J. Clin. Endocrinol. Metab. 2004
24784881 Loss of Function Mutation in the Palmitoyl-Transferase HHAT Leads to Syndromic 46,XY Disorder of Sex Development by Impeding Hedgehog Protein Palmitoylation and Signaling

Callier, P, Calvel, P, Matevossian, A, Makrythanasis, P, Bernard, P, Kurosaka, H, Vannier, A, Thauvin-Robinet, C, Borel, C, Mazaud-Guittot, S, Rolland, A, Desdoits-Lethimonier, C, Guipponi, M, Zimmermann, C, Stévant, I, Kuhne, F, Conne, B, Santoni, F, Lambert, S, Huet, F, Mugneret, F, Jaruzelska, J, Faivre, L, Wilhelm, D, Jégou, B, Trainor, PA, Resh, MD, Antonarakis, SE, Nef, S

PLoS Genet. 2014
11017805 A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy

Umehara, F, Tate, G, Itoh, K, Yamaguchi, N, Douchi, T, Mitsuya, T, Osame, M

Am. J. Hum. Genet. 2000
16390857 A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis

Canto, P, Vilchis, F, Söderlund, D, Reyes, E, Méndez, JP

Mol. Hum. Reprod. 2005
21816240 Novel homozygous mutations in Desert hedgehog gene in patients with 46,XY complete gonadal dysgenesis and prediction of its structural and functional implications by computational methods

Das, DK, Sanghavi, D, Gawde, H, Idicula-Thomas, S, Vasudevan, L

Eur J Med Genet 2011
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
O-acyltransferase activity of HHAT G287V [endoplasmic reticulum membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
46 XY gonadal dysgenesis 14448 Pure gonadal dysgenesis 46,XY (disorder), 46,XY SEX REVERSAL
Authored
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