HACD1

3-hydroxyacyl-CoA dehydratase 1, the group of 3-hydroxyacyl-CoA dehydratase family

Basic information

Region (hg38): 10:17589031-17617374

Previous symbols: [ "PTPLA" ]

Links

ENSG00000165996 ∙ NCBI:9200 ∙ OMIM:610467 ∙ HGNC:9639 ∙ Uniprot:B0YJ81 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital fiber-type disproportion myopathy (Supportive), mode of inheritance: AD
• congenital myopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital myopathy 11	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	Musculoskeletal	23933735; 32426512; 33354762

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HACD1 gene.

• not provided (133 variants)
• Inborn genetic diseases (5 variants)
• not specified (2 variants)
• Congenital myopathy 11 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HACD1 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	21	3	25
missense			54	3	5	62
nonsense	1		1			2
start loss			2		1	3
frameshift	3					3
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region			4	3	3	10
non coding				15	9	24
Total	5	2	60	39	18

Highest pathogenic variant AF is 0.0000197

Variants in HACD1

This is a list of pathogenic ClinVar variants found in the HACD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-17590378-C-G		not specified	Uncertain significance (Sep 21, 2020)
10-17590387-C-G			Uncertain significance (Aug 03, 2022)
10-17590394-A-G			Likely benign (Aug 23, 2023)
10-17590405-T-C			Uncertain significance (Dec 11, 2023)
10-17590422-A-G			Uncertain significance (Aug 21, 2022)
10-17590423-T-C			Uncertain significance (May 18, 2021)
10-17590431-T-C			Uncertain significance (Aug 17, 2022)
10-17590438-G-A			Uncertain significance (Jun 13, 2022)
10-17590447-C-A		Congenital myopathy 11	Pathogenic (Mar 10, 2023)
10-17590448-T-C			Uncertain significance (Nov 30, 2021)
10-17590450-C-T			Likely benign (Sep 10, 2023)
10-17590452-T-C			Uncertain significance (Jul 30, 2022)
10-17590563-C-T			Benign (Jun 19, 2021)
10-17594086-G-A			Benign (Jun 19, 2021)
10-17594183-G-C			Benign (Jun 19, 2021)
10-17594185-A-G			Likely benign (Aug 07, 2021)
10-17594190-T-C			Likely benign (Apr 25, 2023)
10-17594225-G-A			Uncertain significance (Oct 14, 2022)
10-17594225-G-T			Uncertain significance (Apr 14, 2023)
10-17594241-AATAGT-A			Pathogenic (Jun 05, 2022)
10-17594243-T-C			Likely benign (Jan 30, 2024)
10-17594245-G-T		Congenital myopathy 11	Pathogenic (Dec 20, 2013)
10-17594248-G-A			Benign (Jan 29, 2024)
10-17594274-G-C			Uncertain significance (Feb 02, 2022)
10-17594282-AT-A			Pathogenic (Jul 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HACD1	protein_coding	protein_coding	ENST00000361271	7	27419

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.29e-9	0.0561	125699	0	43	125742	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.511	114	130	0.874	0.00000655	1801
Missense in Polyphen		48	55.751	0.86096		697
Synonymous	0.831	37	44.0	0.841	0.00000225	551
Loss of Function	-0.310	13	11.8	1.10	5.00e-7	171

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000199	0.000185
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.000372	0.000370
European (Non-Finnish)	0.000207	0.000202
Middle Eastern	0.00	0.00
South Asian	0.000163	0.000163
Other	0.000363	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. {ECO:0000269|PubMed:18554506}.
• Disease: DISEASE: Myopathy, congenital, with fiber-type disproportion (CFTD) [MIM:255310]: A genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions. {ECO:0000269|PubMed:23933735}. Note=The gene represented in this entry may be involved in disease pathogenesis. A loss-of-function mutation that segregates with the disease was found in four members of a consanguineous family and not identified in unaffected controls. The mutation affects the expression of the mRNA and the produced protein is catalytically inactive. {ECO:0000269|PubMed:23933735}.
• Pathway: Biosynthesis of unsaturated fatty acids - Homo sapiens (human);Fatty acid elongation - Homo sapiens (human);Metabolism of lipids;Fatty acyl-CoA biosynthesis;Metabolism;Fatty acid metabolism;Synthesis of very long-chain fatty acyl-CoAs (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.56

Haploinsufficiency Scores

• pHI: 0.197
• hipred: N
• hipred_score: 0.310
• ghis: 0.445

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Hacd1
• Phenotype: muscle phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: multicellular organism development;sphingolipid biosynthetic process;fatty acid elongation;long-chain fatty-acyl-CoA biosynthetic process;very long-chain fatty acid biosynthetic process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: 3-hydroxyacyl-CoA dehydratase activity;3R-hydroxyacyl-CoA dehydratase activity;very-long-chain 3-hydroxyacyl-CoA dehydratase activity;3-hydroxy-arachidoyl-CoA dehydratase activity;3-hydroxy-behenoyl-CoA dehydratase activity;3-hydroxy-lignoceroyl-CoA dehydratase activity