HHAT G287V doesn't palmitoylate Hh-Np

Stable Identifier
Reaction [transition]
Homo sapiens
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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
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

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

PLoS Genet. 2014
15356051 Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis

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

J. Clin. Endocrinol. Metab. 2004
11017805 A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy

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

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

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

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

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

Eur J Med Genet 2011
Catalyst Activity

O-acyltransferase activity of HHAT G287V [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of HHAT G287V [endoplasmic reticulum membrane]

Name Identifier Synonyms
46 XY gonadal dysgenesis DOID:14448 Pure gonadal dysgenesis 46,XY (disorder), 46,XY SEX REVERSAL
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