CLYBL

citramalyl-CoA lyase, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 13:99606668-99909459

Links

ENSG00000125246 ∙ NCBI:171425 ∙ OMIM:609686 ∙ HGNC:18355 ∙ Uniprot:Q8N0X4 ∙ 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 CLYBL gene.

• Inborn genetic diseases (18 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLYBL 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						0
missense			17	1		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	1	0

Variants in CLYBL

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

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

Position	Type	Phenotype	Significance	ClinVar
13-99606700-C-G		not specified	Uncertain significance (Aug 02, 2021)
13-99606705-C-T		not specified	Uncertain significance (Feb 07, 2023)
13-99606726-C-G		not specified	Uncertain significance (Jan 24, 2023)
13-99606733-C-T		not specified	Uncertain significance (Aug 19, 2023)
13-99606744-G-A		not specified	Uncertain significance (Nov 10, 2022)
13-99606744-G-T		not specified	Uncertain significance (May 31, 2023)
13-99606745-C-T		not specified	Uncertain significance (Nov 03, 2023)
13-99606747-C-G		not specified	Uncertain significance (Jan 29, 2024)
13-99772895-G-A		not specified	Uncertain significance (Feb 14, 2023)
13-99772978-G-T		not specified	Uncertain significance (Dec 17, 2023)
13-99858871-G-A		not specified	Uncertain significance (May 10, 2023)
13-99858891-C-G		not specified	Uncertain significance (Jan 30, 2024)
13-99858991-G-A		not specified	Uncertain significance (Jan 23, 2024)
13-99859018-C-G		not specified	Uncertain significance (Oct 25, 2022)
13-99864842-G-A		not specified	Likely benign (Oct 25, 2022)
13-99864869-G-C		not specified	Uncertain significance (May 11, 2022)
13-99864878-G-A		not specified	Uncertain significance (Sep 14, 2021)
13-99864900-G-A		not specified	Uncertain significance (Mar 04, 2024)
13-99866248-A-G		not specified	Uncertain significance (Nov 10, 2022)
13-99866261-C-A		not specified	Uncertain significance (Sep 12, 2023)
13-99866300-T-C		not specified	Uncertain significance (Dec 14, 2021)
13-99866381-G-A		not specified	Uncertain significance (Oct 27, 2023)
13-99866392-G-A		not specified	Uncertain significance (Dec 14, 2021)
13-99866396-T-C		not specified	Uncertain significance (Jan 02, 2024)
13-99871014-G-C		not specified	Uncertain significance (Feb 12, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLYBL	protein_coding	protein_coding	ENST00000376360	8	290469

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.64e-9	0.222	118661	121	6966	125748	0.0286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0788	183	180	1.02	0.00000947	2181
Missense in Polyphen		61	61.305	0.99503		723
Synonymous	-0.833	80	71.1	1.13	0.00000396	701
Loss of Function	0.582	15	17.6	0.850	0.00000102	198

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0327	0.0326
Ashkenazi Jewish	0.0498	0.0502
East Asian	0.0497	0.0500
Finnish	0.0358	0.0356
European (Non-Finnish)	0.0272	0.0271
Middle Eastern	0.0497	0.0500
South Asian	0.0237	0.0231
Other	0.0338	0.0341

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mitochondrial citramalyl-CoA lyase indirectly involved in the vitamin B12 metabolism (PubMed:29056341). Converts citramalyl-CoA into acetyl-CoA and pyruvate in the C5- dicarboxylate catabolism pathway (PubMed:29056341). The C5- dicarboxylate catabolism pathway is required to detoxify itaconate, a vitamin B12-poisoning metabolite (PubMed:29056341). Also acts as a malate synthase in vitro, converting glyoxylate and acetyl-CoA to malate (PubMed:24334609, PubMed:29056341). Also acts as a beta-methylmalate synthase in vitro, by mediating conversion of glyoxylate and propionyl-CoA to beta-methylmalate (PubMed:24334609, PubMed:29056341). Also has very weak citramalate synthase activity in vitro (PubMed:24334609, PubMed:29056341). {ECO:0000269|PubMed:24334609, ECO:0000269|PubMed:29056341}.
• Pathway: TCA cycle (Consensus)

Recessive Scores

• pRec: 0.323

Intolerance Scores

• loftool: 0.889
• rvis_EVS: 0.77
• rvis_percentile_EVS: 87.06

Haploinsufficiency Scores

• pHI: 0.195
• hipred: N
• hipred_score: 0.345
• ghis: 0.396

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.848

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clybl

Gene ontology

• Biological process: protein homotrimerization;regulation of cobalamin metabolic process
• Cellular component: mitochondrion
• Molecular function: magnesium ion binding;malate synthase activity;(3S)-citramalyl-CoA lyase activity