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.

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.

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				19	3	22
missense		1	50	7	5	63
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			1		2	3
non coding				5	10	15
Total	0	3	51	31	18

Variants in ATIC

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

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

Position	Type	Phenotype	Significance	ClinVar
2-215312084-T-G		AICA-ribosiduria	Benign (Jul 14, 2021)
2-215312147-C-T		Intellectual disability • AICA-ribosiduria	Benign/Likely benign (Dec 12, 2023)
2-215312255-G-A			Benign (Feb 01, 2023)
2-215312530-G-C		not specified	Uncertain significance (Feb 23, 2023)
2-215312569-C-G			Uncertain significance (Sep 01, 2022)
2-215312580-C-T		ATIC-related disorder	Likely benign (Mar 26, 2019)
2-215312590-G-A		not specified	Uncertain significance (Oct 26, 2022)
2-215312609-C-GCA		AICA-ribosiduria	Uncertain significance (Jan 15, 2019)
2-215312609-C-GGA		AICA-ribosiduria	Pathogenic (Jun 01, 2004)
2-215318046-A-T		AICA-ribosiduria	Benign (Jul 14, 2021)
2-215318174-C-T		not specified	Uncertain significance (Mar 31, 2024)
2-215318175-G-A			Likely benign (Aug 04, 2023)
2-215318222-C-T		not specified	Uncertain significance (Nov 06, 2023)
2-215319657-T-A		ATIC-related disorder	Benign (Nov 22, 2023)
2-215319677-G-A		not specified	Uncertain significance (Dec 19, 2022)
2-215319701-A-G			Uncertain significance (Aug 08, 2023)
2-215319713-T-C		not specified	Uncertain significance (Oct 26, 2021)
2-215319722-A-G			Benign (Dec 31, 2019)
2-215321102-C-T			Benign (Jan 29, 2024)
2-215325297-C-G		AICA-ribosiduria • ATIC-related disorder	Benign (Jan 29, 2024)
2-215325316-G-A			Likely benign (Jan 12, 2024)
2-215325330-G-A			Likely pathogenic (Aug 04, 2023)
2-215325344-C-G			Likely benign (Jul 23, 2023)
2-215325968-A-C		AICA-ribosiduria	Benign (Jan 29, 2024)
2-215325969-G-A		AICA-ribosiduria	Likely benign (Apr 11, 2022)

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