FICD

FIC domain protein adenylyltransferase

Basic information

Region (hg38): 12:108515277-108525837

Links

ENSG00000198855

∙ NCBI:11153 ∙ ∙ HGNC:18416 ∙ Uniprot:Q9BVA6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

spastic paraplegia 92, autosomal recessive (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 92, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	36136088

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FICD gene.

not_specified (69 variants)
not_provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FICD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000007076.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			68 clinvar	1 clinvar	1 clinvar	70
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	68	1	2

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FICD	protein_coding	protein_coding	ENST00000552695	2	10653

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0102	0.949	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.315	278	293	0.948	0.0000192	2982
Missense in Polyphen		102	109.82	0.92882		1057
Synonymous	-0.881	147	134	1.10	0.0000101	953
Loss of Function	1.77	5	11.5	0.436	4.90e-7	148

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000606	0.000604
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.0000544	0.0000544
South Asian	0.000106	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: 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 (By similarity). 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). 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). {ECO:0000250|UniProtKB:A0A061I403, ECO:0000269|PubMed:22266942, ECO:0000269|PubMed:25435325, ECO:0000269|PubMed:25601083, ECO:0000305|PubMed:19362538}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

loftool: 0.187
rvis_EVS: -0.84
rvis_percentile_EVS: 11.36

Haploinsufficiency Scores

pHI: 0.164
hipred: N
hipred_score: 0.325
ghis: 0.560

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.931

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Ficd
Phenotype

Gene ontology

Biological process: response to unfolded protein;protein adenylylation;negative regulation of GTPase activity;response to endoplasmic reticulum stress;protein deadenylylation;regulation of IRE1-mediated unfolded protein response
Cellular component: integral component of endoplasmic reticulum membrane
Molecular function: ATP binding;Hsp70 protein binding;identical protein binding;protein homodimerization activity;protein adenylylhydrolase activity;chaperone binding;protein adenylyltransferase activity