HMGCLL1

3-hydroxymethyl-3-methylglutaryl-CoA lyase like 1

Basic information

Region (hg38): 6:55434373-55579197

Links

ENSG00000146151 ∙ NCBI:54511 ∙ OMIM:619050 ∙ HGNC:21359 ∙ Uniprot:Q8TB92 ∙ 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 HMGCLL1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HMGCLL1 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			26			26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	26	0	0

Variants in HMGCLL1

This is a list of pathogenic ClinVar variants found in the HMGCLL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-55435675-G-A		not specified	Uncertain significance (Dec 07, 2021)
6-55435732-C-A		not specified	Uncertain significance (Jun 25, 2024)
6-55435742-T-A		not specified	Uncertain significance (Jan 03, 2024)
6-55439472-C-T		not specified	Uncertain significance (Dec 16, 2022)
6-55439475-C-T		not specified	Uncertain significance (Jul 16, 2024)
6-55439502-T-C		not specified	Uncertain significance (Sep 17, 2021)
6-55439544-C-T		not specified	Uncertain significance (Aug 17, 2021)
6-55495429-G-A		not specified	Uncertain significance (Jun 07, 2023)
6-55495430-T-A		not specified	Uncertain significance (Jun 07, 2023)
6-55495492-G-T		not specified	Uncertain significance (Nov 18, 2022)
6-55495538-G-C		not specified	Uncertain significance (Jan 24, 2024)
6-55495553-T-C		not specified	Uncertain significance (Dec 13, 2022)
6-55495555-G-A		not specified	Uncertain significance (Oct 01, 2024)
6-55495562-C-T		not specified	Uncertain significance (Oct 02, 2023)
6-55495596-T-A		not specified	Uncertain significance (Sep 27, 2022)
6-55499252-G-A		not specified	Uncertain significance (Nov 13, 2024)
6-55514072-C-T		not specified	Uncertain significance (Feb 16, 2023)
6-55514076-C-T		not specified	Uncertain significance (Mar 31, 2023)
6-55514134-C-A		not specified	Uncertain significance (Jun 07, 2023)
6-55514150-T-G		not specified	Uncertain significance (Mar 20, 2023)
6-55514190-C-G		not specified	Uncertain significance (Apr 22, 2022)
6-55516552-G-A		not specified	Uncertain significance (Jan 23, 2023)
6-55516573-T-A		not specified	Uncertain significance (Jul 30, 2024)
6-55541742-C-A		not specified	Uncertain significance (May 22, 2023)
6-55541742-C-G		not specified	Uncertain significance (Nov 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HMGCLL1	protein_coding	protein_coding	ENST00000398661	10	144846

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.98e-7	0.773	124635	0	159	124794	0.000637

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.486	218	199	1.10	0.00000951	2397
Missense in Polyphen		92	84.258	1.0919		1058
Synonymous	0.318	69	72.4	0.952	0.00000385	736
Loss of Function	1.34	13	19.4	0.671	9.83e-7	233

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00321	0.00319
Ashkenazi Jewish	0.00	0.00
East Asian	0.00104	0.000946
Finnish	0.00	0.00
European (Non-Finnish)	0.000226	0.000221
Middle Eastern	0.00104	0.000946
South Asian	0.000728	0.000719
Other	0.000502	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy- 3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis, the products of which support energy production in nonhepatic animal tissues. {ECO:0000269|PubMed:22847177, ECO:0000269|PubMed:22865860}.
• Pathway: Butanoate metabolism - Homo sapiens (human);Peroxisome - Homo sapiens (human);Synthesis and degradation of ketone bodies - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);ketogenesis;Metabolism of lipids;leucine degradation;Metabolism;Synthesis of Ketone Bodies;Ketone body metabolism (Consensus)

Recessive Scores

• pRec: 0.165

Intolerance Scores

• loftool: 0.327
• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.73

Haploinsufficiency Scores

• pHI: 0.120
• hipred: N
• hipred_score: 0.289
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.126

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hmgcll1

Gene ontology

• Biological process: leucine catabolic process;lipid metabolic process;ketone body biosynthetic process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;membrane;perinuclear region of cytoplasm
• Molecular function: hydroxymethylglutaryl-CoA lyase activity;metal ion binding