HACL1

2-hydroxyacyl-CoA lyase 1

Basic information

Region (hg38): 3:15560698-15601852

Previous symbols: [ "HPCL" ]

Links

ENSG00000131373 ∙ NCBI:26061 ∙ OMIM:604300 ∙ HGNC:17856 ∙ Uniprot:Q9UJ83 ∙ 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 HACL1 gene.

• Inborn genetic diseases (30 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HACL1 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				2	1	3
missense			28	2	1	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	28	4	3

Variants in HACL1

This is a list of pathogenic ClinVar variants found in the HACL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-15560857-G-A		HACL1-related disorder	Likely benign (Mar 18, 2019)
3-15560869-A-G		not specified	Uncertain significance (Feb 15, 2023)
3-15563368-C-T		not specified	Uncertain significance (Dec 13, 2022)
3-15563369-G-A		not specified	Uncertain significance (Nov 03, 2023)
3-15563448-G-A		HACL1-related disorder	Likely benign (Jul 01, 2022)
3-15563496-C-T		not specified	Uncertain significance (Mar 22, 2023)
3-15563515-G-A		not specified	Uncertain significance (Mar 08, 2024)
3-15563534-T-C		not specified	Uncertain significance (Sep 26, 2023)
3-15564556-A-G			Likely benign (Jul 01, 2022)
3-15567878-C-G		not specified	Uncertain significance (Nov 14, 2023)
3-15567909-C-A		not specified	Uncertain significance (Apr 25, 2023)
3-15567912-T-C		HACL1-related disorder	Likely benign (Mar 20, 2019)
3-15567941-C-A		HACL1-related disorder	Likely benign (Apr 25, 2023)
3-15567941-C-T		not specified	Likely benign (Feb 12, 2024)
3-15567945-A-C		HACL1-related disorder	Likely benign (Jun 11, 2019)
3-15567979-G-C		not specified	Uncertain significance (Oct 12, 2021)
3-15567997-T-C		not specified	Uncertain significance (Dec 15, 2022)
3-15567998-C-T		not specified	Uncertain significance (Oct 27, 2023)
3-15568433-T-C		not specified	Uncertain significance (Feb 15, 2023)
3-15568465-C-T		not specified	Uncertain significance (Jun 29, 2023)
3-15568502-C-T		not specified	Uncertain significance (Mar 14, 2023)
3-15568516-G-A		not specified	Uncertain significance (Nov 30, 2022)
3-15568563-C-T		HACL1-related disorder	Benign (Oct 29, 2019)
3-15571684-T-C		not specified	Uncertain significance (Dec 21, 2023)
3-15571748-T-C		not specified	Uncertain significance (Oct 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HACL1	protein_coding	protein_coding	ENST00000321169	17	41128

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.48e-12	0.654	125593	0	154	125747	0.000613

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0436	321	319	1.01	0.0000158	3803
Missense in Polyphen		83	87.66	0.94684		979
Synonymous	0.0645	107	108	0.992	0.00000536	1094
Loss of Function	1.53	22	31.2	0.705	0.00000132	397

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00190	0.00190
Ashkenazi Jewish	0.000410	0.000397
East Asian	0.000327	0.000326
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000585	0.000571
Middle Eastern	0.000327	0.000326
South Asian	0.000501	0.000457
Other	0.00118	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes a carbon-carbon cleavage reaction; cleaves a 2-hydroxy-3-methylacyl-CoA into formyl-CoA and a 2-methyl-branched fatty aldehyde.
• Pathway: Peroxisome - Homo sapiens (human);Oxidation of Branched Chain Fatty Acids;Refsum Disease;Phytanic Acid Peroxisomal Oxidation;Metabolism of lipids;Metabolism of proteins;Alpha-oxidation of phytanate;Peroxisomal lipid metabolism;Metabolism;Peroxisomal protein import;Fatty acid metabolism;fatty acid α-oxidation III;Phytanic acid peroxisomal oxidation;fatty acid α-oxidation (Consensus)

Recessive Scores

• pRec: 0.0787

Intolerance Scores

• loftool: 0.937
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.73

Haploinsufficiency Scores

• pHI: 0.0922
• hipred: N
• hipred_score: 0.219
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.799

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hacl1
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: fatty acid alpha-oxidation;protein targeting to peroxisome;protein complex oligomerization
• Cellular component: peroxisome;peroxisomal matrix;cytosol
• Molecular function: magnesium ion binding;signaling receptor binding;protein binding;carbon-carbon lyase activity;thiamine pyrophosphate binding;identical protein binding;cofactor binding