HMGCLL1

Chr 6

3-hydroxy-3-methylglutaryl-CoA lyase like 1

Also known as: ERCHL, bA418P12.1, er-cHL

NCBI Gene: 54511ENSG00000146151UniProt: Q8TB92

Enables hydroxymethylglutaryl-CoA lyase activity. Involved in ketone body biosynthetic process. Located in several cellular components, including cytosol; endoplasmic reticulum; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
9
Pathogenic / LP
70
ClinVar variants
2
Pubs (1 yr)
-0.5
Missense Z
1.07
LOEUF
Clinical Summary— HMGCLL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 59 VUS of 70 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.34
OE 0.67 (0.44–1.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.49Z-score
OE missense 1.10 (0.98–1.23)
218 obs / 198.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.67 (0.44–1.07)
0≤0.351.4
Missense OE1.10 (0.98–1.23)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 13 / 19.4Missense obs/exp: 218 / 198.7Syn Z: 0.32
DNGOF
DN
0.81top 10%
GOF
0.6541th %ile
LOF
0.3163th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

70 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS59
Likely Benign2
7
Pathogenic
2
Likely Pathogenic
59
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
53
6
0
59
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total05416070

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

HMGCLL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
In-depth investigation of genome to refine QTL positions for spontaneous sex-reversal in XX rainbow trout
Dehaullon A et al.·PLoS One
2025
An integrated pathological research for precise diagnosis of schizophrenia combining LC-MS/1H NMR metabolomics and transcriptomics.
Wang T et al.·Clin Chim Acta
2022
Large deletions in the DNA primase large subunit PRIM2 are associated with NADP-malate dehydrogenase activity in a porcine F2 cross
Falker-Gieske C et al.·Anim Genet
2026
Genome Imputation for Genome-Wide Association Study of Reproductive Traits in Chinese Duroc, Landrace, and Yorkshire Pigs: Strategy and Validation.
Zhou J et al.·Animals (Basel)
2026
Identification of key proteins as potential biomarkers associated with post-infarction complications in diabetics
Wu W et al.·Int J Immunopathol Pharmacol
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients