HACL1

protein-coding

2-hydroxyacyl-CoA lyase 1

Gene summary

Enables several functions, including 2-hydroxyacyl-CoA lyase activity; ATP binding activity; and cation binding activity. Involved in fatty acid alpha-oxidation; phytanic acid metabolic process; and protein targeting to peroxisome. Located in peroxisome. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

HPCL

MANE transcript

NM_012260.4

Inheritance

—

ClinVar variants

P:1U:121B:13

Top phenotype

HACL1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr3:15,560,699-15,601,852

External References & Databases

Ensembl (ENSG00000131373)

Transcript & Mutation Effects

hg38 • Region Span ~41.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HACL1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 111

HACL1-related disorderTotal: 7

not providedTotal: 4

Familial hypercholesterolemiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012260.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	4 clinvar	1 clinvar	8
missense	1 clinvar		109 clinvar	7 clinvar	1 clinvar	118
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	1	0	121	11	2	135

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 80 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012260.4	RefSeq	NP_036392.2	17	MANE Select
ENST00000321169.10	Ensembl	ENSP00000323811.5	17	MANE Select
NM_001284413.2	RefSeq	NP_001271342.1	16	Standard
NM_001284415.2	RefSeq	NP_001271344.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Peroxisome - Homo sapiens (human)
Oxidation of Branched Chain Fatty Acids
Refsum Disease
Phytanic Acid Peroxisomal Oxidation
Metabolism of lipids

Biological Process

fatty acid alpha-oxidation
protein targeting to peroxisome
protein complex oligomerization

Molecular Function

magnesium ion binding
signaling receptor binding
protein binding
carbon-carbon lyase activity
thiamine pyrophosphate binding

Cellular Component

peroxisome
peroxisomal matrix
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321169
Coding exons: 17
Length: 41128
Individuals with no LoFs: 125593
Homozygous LoFs: 0
Heterozygous LoFs: 154
Defined: 125747
p: 0.000613

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0436	321	319	1.01	0.0000158	3803
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.0014	0.0014	notable
Ashkenazi Jewish	0.00041	0.00040	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00058	0.00057	rare
South Asian	0.00050	0.00046	rare
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.0787

Intolerance Scores

LoFtool: 0.937
RVIS EVS: -0.42
RVIS percentile EVS: 25.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.799

Gene Damage Prediction

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