LIPE

Chr 19

lipase E, hormone sensitive type

Also known as: AOMS4, FPLD6, HSL, LHS, REH

NCBI Gene: 3991 ENSG00000079435 UniProt: Q05469

This gene encodes hormone-sensitive lipase, which hydrolyzes triglycerides to free fatty acids in adipose tissue and converts cholesteryl esters to free cholesterol for steroid hormone production in steroidogenic tissues. Mutations cause familial partial lipodystrophy type 6, inherited in an autosomal recessive pattern. The gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene has a long and a short form, generated by use of alternative translational start codons. The long form is expressed in steroidogenic tissues such as testis, where it converts cholesteryl esters to free cholesterol for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored triglycerides to free fatty acids. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.85

Clinical Summary— LIPE

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Gene-Disease Validity (ClinGen)

LIPE-related familial partial lipodystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 182 VUS of 280 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.000

Z-score 2.30

OE 0.61 (0.44–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.95Z-score

OE missense 0.89 (0.83–0.96)

582 obs / 650.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.44–0.85)

0≤0.351.4

Missense OE?0.89 (0.83–0.96)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 24 / 39.7Missense obs/exp: 582 / 650.3Syn Z: 0.12

This gene — mechanism propensity

0.6357th %ile

GOF

0.6051th %ile

LOF

0.3648th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

280 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic3

VUS182

Likely Benign47

Benign36

Conflicting4

Pathogenic

Likely Pathogenic

182

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	0	0	0	3
Likely Pathogenic	3	0	0	0	3
VUS	2	178	1	1	182
Likely Benign	0	19	5	23	47
Benign	0	10	19	7	36
Conflicting	—				4
Total	8	207	25	31	275

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap LIPE — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →