CHAC1

ChaC glutathione specific gamma-glutamylcyclotransferase 1

Basic information

Region (hg38): 15:40952961-40956512

Links

ENSG00000128965 ∙ NCBI:79094 ∙ OMIM:614587 ∙ HGNC:28680 ∙ Uniprot:Q9BUX1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHAC1 gene.

• Inborn genetic diseases (15 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHAC1 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			13			13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2			2
Total	0	0	15	1	0

Variants in CHAC1

This is a list of pathogenic ClinVar variants found in the CHAC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-40953483-C-G		not specified	Uncertain significance (Jul 14, 2021)
15-40953497-C-T		not specified	Uncertain significance (Feb 15, 2023)
15-40953503-G-A		not specified	Uncertain significance (Jan 23, 2024)
15-40953552-G-A		not specified	Uncertain significance (Dec 18, 2023)
15-40953608-A-G		not specified	Uncertain significance (Nov 21, 2022)
15-40953666-G-A		not specified	Uncertain significance (Jun 28, 2022)
15-40953736-C-G		not specified	Uncertain significance (Dec 01, 2022)
15-40953740-C-T		not specified	Uncertain significance (Oct 30, 2023)
15-40953754-G-A			Likely benign (Mar 01, 2020)
15-40953761-T-C		not specified	Uncertain significance (Sep 26, 2022)
15-40953806-G-A		not specified	Uncertain significance (Jun 07, 2023)
15-40953809-A-G		not specified	Uncertain significance (Sep 22, 2023)
15-40955384-G-A		Malignant tumor of prostate	Uncertain significance (-)
15-40955386-G-T		not specified	Uncertain significance (Jun 29, 2022)
15-40955414-G-C		not specified	Uncertain significance (Apr 12, 2022)
15-40955489-C-G		not specified	Uncertain significance (Oct 26, 2021)
15-40955566-G-T		not specified	Uncertain significance (Mar 27, 2023)
15-40955572-C-T		not specified	Uncertain significance (Mar 23, 2022)
15-40955691-G-A		not specified	Uncertain significance (Sep 20, 2023)
15-40955715-G-A		not specified	Uncertain significance (Apr 12, 2023)
15-40955751-G-A		not specified	Uncertain significance (Jan 03, 2024)
15-40955764-C-T		not specified	Uncertain significance (Oct 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHAC1	protein_coding	protein_coding	ENST00000446533	3	3551

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000206	0.745	125716	0	22	125738	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.244	152	161	0.946	0.00000859	1677
Missense in Polyphen		51	64.044	0.79633		679
Synonymous	-0.221	73	70.6	1.03	0.00000421	564
Loss of Function	1.00	7	10.5	0.666	5.43e-7	97

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the cleavage of glutathione into 5-oxo-L- proline and a Cys-Gly dipeptide. Acts specifically on glutathione, but not on other gamma-glutamyl peptides (PubMed:27913623). Glutathione depletion is an important factor for apoptosis initiation and execution. Acts as a pro-apoptotic component of the unfolded protein response pathway by mediating the pro-apoptotic effects of the ATF4-ATF3-DDIT3/CHOP cascade (PubMed:19109178). Negative regulator of Notch signaling pathway involved in embryonic neurogenesis: acts by inhibiting Notch cleavage by furin, maintaining Notch in an immature inactive form, thereby promoting neurogenesis in embryos (PubMed:22445366). {ECO:0000269|PubMed:19109178, ECO:0000269|PubMed:22445366, ECO:0000269|PubMed:27913623}.
• Pathway: Glutathione conjugation;Phase II - Conjugation of compounds;Biological oxidations;Metabolism;Glutathione synthesis and recycling (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.393
• rvis_EVS: 0.86
• rvis_percentile_EVS: 88.69

Haploinsufficiency Scores

• pHI: 0.469
• hipred: N
• hipred_score: 0.238
• ghis: 0.396

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.600

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chac1

Gene ontology

• Biological process: glutathione biosynthetic process;glutathione catabolic process;response to unfolded protein;Notch signaling pathway;negative regulation of protein processing;neurogenesis;negative regulation of Notch signaling pathway;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
• Cellular component: cytoplasm;trans-Golgi network;cytosol
• Molecular function: gamma-glutamylcyclotransferase activity;Notch binding;protein binding;glutathione specific gamma-glutamylcyclotransferase activity