ATIC

5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase, the group of Purinosome

Basic information

Region (hg38): 2:215311956-215349773

Links

ENSG00000138363 ∙ NCBI:471 ∙ OMIM:601731 ∙ HGNC:794 ∙ Uniprot:P31939 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• AICA-ribosiduria (Definitive), mode of inheritance: AR
• AICA-ribosiduria (Supportive), mode of inheritance: AR
• AICA-ribosiduria (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
AICA-ribosuria due to ATIC deficiency	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	Biochemical; Craniofacial; Dermatologic; Neurologic; Ophthalmologic	15114530; 32557644

ClinVar

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

• not_specified (71 variants)
• not_provided (64 variants)
• AICA-ribosiduria (17 variants)
• ATIC-related_disorder (8 variants)
• See_cases (2 variants)
• Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATIC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004044.7. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				21	2	23
missense	1	3	83	10	5	102
nonsense	1					1
start loss						0
frameshift	1	1	1			3
splice donor/acceptor (+/-2bp)		2				2
Total	3	6	84	31	7

Highest pathogenic variant AF is 0.000047793375

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATIC	protein_coding	protein_coding	ENST00000236959	16	37948

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.01e-19	0.00836	125613	0	135	125748	0.000537

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.482	352	327	1.07	0.0000179	3844
Missense in Polyphen		140	141.44	0.98979		1671
Synonymous	-1.30	143	125	1.15	0.00000780	1169
Loss of Function	0.421	30	32.6	0.920	0.00000170	397

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000589	0.000589
Ashkenazi Jewish	0.00139	0.00139
East Asian	0.000598	0.000598
Finnish	0.00	0.00
European (Non-Finnish)	0.000633	0.000633
Middle Eastern	0.000598	0.000598
South Asian	0.000588	0.000555
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis. {ECO:0000269|PubMed:14966129}.
• Disease: DISEASE: AICAR transformylase/IMP cyclohydrolase deficiency (AICAR) [MIM:608688]: A neurologically devastating inborn error of purine biosynthesis. Patients excrete massive amounts of AICA- riboside in the urine and accumulate AICA-ribotide and its derivatives in erythrocytes and fibroblasts. AICAR causes profound mental retardation, epilepsy, dysmorphic features and congenital blindness. {ECO:0000269|PubMed:15114530}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Antimetabolite Pathway - Folate Cycle, Pharmacodynamics;One carbon pool by folate - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Methotrexate Pathway (Cancer Cell), Pharmacodynamics;Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;One Carbon Metabolism;Purine metabolism;Metabolism of nucleotides;Folate metabolism;Metabolism;Nucleobase biosynthesis;Purine nucleotides nucleosides metabolism;inosine-5,-phosphate biosynthesis;Purine ribonucleoside monophosphate biosynthesis;purine nucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.700

Intolerance Scores

• loftool: 0.615
• rvis_EVS: 0.25
• rvis_percentile_EVS: 69.62

Haploinsufficiency Scores

• pHI: 0.864
• hipred: Y
• hipred_score: 0.721
• ghis: 0.598

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.968

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atic

Gene ontology

• Biological process: brainstem development;nucleobase-containing compound metabolic process;'de novo' IMP biosynthetic process;nucleoside metabolic process;purine ribonucleoside monophosphate biosynthetic process;response to inorganic substance;cerebellum development;cerebral cortex development;animal organ regeneration;dihydrofolate metabolic process;tetrahydrofolate biosynthetic process;cellular response to interleukin-7
• Cellular component: cytosol;plasma membrane;membrane;extracellular exosome
• Molecular function: IMP cyclohydrolase activity;phosphoribosylaminoimidazolecarboxamide formyltransferase activity;protein homodimerization activity;cadherin binding