FICD

Chr 12q23.3

FIC domain protein adenylyltransferase

Aliases:: HYPE, HIP13
MANE:: ENST00000552695.6

OMIM: 620875 ↗NCBI: 11153 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

FICD · Q9BVA6

v62025-08-01

Predicted Aligned Error matrix for FICD — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

83.6/ 100

Confident

458 residues

Confidence breakdown

Very high(≥ 90)70%
Confident(70–90)8%
Low(50–70)6%
Very low(< 50)15%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Childhood onset hereditary spastic paraplegia
BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Monogenic diabetes
BIALLELIC, autosomal or pseudoautosomal
Neonatal diabetes
BIALLELIC, autosomal or pseudoautosomal
DDG2P
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

spastic paraplegia 92, autosomal recessive
0.48
self-injurious ideation
0.28
alcohol drinking
0.25
Neonatal insulin-dependent diabetes mellitus
0.25
Neurodevelopmental delay
0.23
Abnormality of the skeletal system
0.23
hypothyroidism
0.22
urolithiasis
0.20
stroke disorder
0.19
diabetes mellitus
0.19

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Protein adenylyltransferase FICD

Protein that can both mediate the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context (By similarity). The side chain of Glu-231 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place (PubMed:36136088). Acts as a key regulator of the ERN1/IRE1-mediated unfolded protein response (UPR) by mediating AMPylation or de-AMPylation of HSPA5/BiP (PubMed:25601083, PubMed:36136088). In unstressed cells, acts as an adenylyltransferase by mediating AMPylation of HSPA5/BiP at 'Thr-518', thereby inactivating it (By similarity). In response to endoplasmic reticulum stress, acts as a phosphodiesterase by mediating removal of ATP (de-AMPylation) from HSPA5/BiP at 'Thr-518', leading to restore HSPA5/BiP activity (By similarity). Although it is able to AMPylate RhoA, Rac and Cdc42 Rho GTPases in vitro, Rho GTPases do not constitute physiological substrates (PubMed:19362538, PubMed:25601083)