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.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			44	1	1	46
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	44	1	2

Variants in FICD

This is a list of pathogenic ClinVar variants found in the FICD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-108516986-C-T		not specified	Uncertain significance (Jun 22, 2021)
12-108517038-C-G		not specified	Uncertain significance (Oct 25, 2023)
12-108517039-C-T		not specified	Uncertain significance (Nov 26, 2024)
12-108517040-G-A		not specified	Uncertain significance (Mar 01, 2024)
12-108517055-C-T		not specified	Likely benign (Sep 26, 2023)
12-108517078-T-G		not specified	Uncertain significance (Oct 03, 2022)
12-108517141-G-A		not specified	Uncertain significance (Feb 09, 2025)
12-108517160-G-A		not specified	Uncertain significance (Jan 10, 2023)
12-108517237-G-A		not specified	Uncertain significance (Feb 05, 2025)
12-108518417-A-G		not specified	Uncertain significance (Jun 07, 2023)
12-108518442-A-T		not specified	Uncertain significance (Jun 11, 2024)
12-108518445-T-C		not specified	Uncertain significance (Aug 28, 2024)
12-108518484-T-C		not specified	Uncertain significance (Jun 26, 2024)
12-108518508-C-T		not specified	Uncertain significance (Aug 19, 2024)
12-108518516-G-A		not specified	Uncertain significance (Oct 12, 2022)
12-108518522-G-A		not specified	Uncertain significance (Mar 29, 2023)
12-108518523-C-T		not specified	Uncertain significance (May 03, 2023)
12-108518528-A-G		not specified	Uncertain significance (Apr 05, 2023)
12-108518547-C-G		not specified	Uncertain significance (Nov 08, 2022)
12-108518547-C-T		not specified	Uncertain significance (Apr 05, 2023)
12-108518574-C-T		not specified	Uncertain significance (Mar 01, 2024)
12-108518593-A-T		not specified	Uncertain significance (Feb 06, 2025)
12-108518604-T-C		not specified	Uncertain significance (Dec 14, 2024)
12-108518612-T-C		not specified	Uncertain significance (Dec 22, 2023)
12-108518622-A-C			Benign (Jun 26, 2018)

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

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