LDAH

Summary

LDAH (lipid droplet associated hydrolase, HGNC:26145) is a protein-coding gene on chromosome 2p24.1, encoding Lipid droplet-associated hydrolase (Q9H6V9). Probable serine lipid hydrolase associated with lipid droplets.

Predicted to enable sterol ester esterase activity. Involved in cholesterol homeostasis and intracellular triglyceride homeostasis. Acts upstream of with a positive effect on lipid droplet fusion. Located in endoplasmic reticulum and lipid droplet.

Source: NCBI Gene 60526 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_021925

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26145
Approved symbol	LDAH
Name	lipid droplet associated hydrolase
Location	2p24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21820
Ensembl gene	ENSG00000118961
Ensembl biotype	protein_coding
OMIM	613570
Entrez	60526

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 retained_intron

ENST00000237822, ENST00000381090, ENST00000402479, ENST00000403006, ENST00000412261, ENST00000419825, ENST00000432947, ENST00000435420, ENST00000440866, ENST00000470099, ENST00000541941, ENST00000619656, ENST00000626491, ENST00000911672, ENST00000911673, ENST00000943495

RefSeq mRNA: 7 — MANE Select: NM_021925 NM_001282719, NM_001282720, NM_001282721, NM_001282722, NM_001282723, NM_001282724, NM_021925

CCDS: CCDS1702, CCDS62864, CCDS62865, CCDS74488, CCDS74489

Canonical transcript exons

ENST00000237822 — 7 exons

Exon	Start	End
ENSE00000802786	20739971	20740205
ENSE00001070699	20684031	20687094
ENSE00001276763	20801310	20801465
ENSE00001553878	20823037	20823101
ENSE00003534868	20701570	20701652
ENSE00003539941	20790255	20790398
ENSE00003646279	20774810	20774979

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 91.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0606 / max 234.2335, expressed in 1734 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27148	10.8446	1730
27147	0.2160	117

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	91.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.43	gold quality
islet of Langerhans	UBERON:0000006	85.27	gold quality
ventricular zone	UBERON:0003053	84.96	gold quality
right adrenal gland	UBERON:0001233	84.42	gold quality
right adrenal gland cortex	UBERON:0035827	83.75	gold quality
ganglionic eminence	UBERON:0004023	83.73	gold quality
cortical plate	UBERON:0005343	83.66	gold quality
esophagus squamous epithelium	UBERON:0006920	83.39	gold quality
palpebral conjunctiva	UBERON:0001812	83.14	gold quality
stromal cell of endometrium	CL:0002255	83.03	gold quality
left adrenal gland	UBERON:0001234	83.03	gold quality
adrenal gland	UBERON:0002369	82.74	gold quality
rectum	UBERON:0001052	82.65	gold quality
embryo	UBERON:0000922	82.59	gold quality
left adrenal gland cortex	UBERON:0035825	82.49	gold quality
secondary oocyte	CL:0000655	82.36	gold quality
eye	UBERON:0000970	81.81	gold quality
adrenal cortex	UBERON:0001235	81.46	gold quality
mucosa of transverse colon	UBERON:0004991	79.61	gold quality
renal glomerulus	UBERON:0000074	79.48	gold quality
metanephros	UBERON:0000081	79.47	gold quality
endometrium	UBERON:0001295	79.29	gold quality
nephron tubule	UBERON:0001231	79.23	gold quality
gall bladder	UBERON:0002110	78.57	gold quality
popliteal artery	UBERON:0002250	78.55	gold quality
tibial artery	UBERON:0007610	78.53	gold quality
adult mammalian kidney	UBERON:0000082	78.52	gold quality
pancreas	UBERON:0001264	78.44	gold quality
kidney	UBERON:0002113	78.05	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting LDAH, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-944	99.82	70.85	3042

Literature-anchored findings (GeneRIF, showing 3)

• Our results provide further support for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in Eastern Asian populations (PMID:22662242)
• The data identify lipid droplet-associated serine hydrolase (LDAH) a candidate target to promote reverse cholesterol transport from atherosclerotic lesions. (PMID:24357060)
• We then amassed convergent genomic evidence showing population level associations between LDAHexpression and occurrence of prostate cancer . We further identified loss of LDAH in both tissues and cell lines derived from human prostate cancer, and generated Ldah-/- mouse model, which recapitulated many of the clinical findings in DGAP056. (PMID:30169630)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ldah	ENSDARG00000079796
mus_musculus	Ldah	ENSMUSG00000037669
rattus_norvegicus	Ldah	ENSRNOG00000021475
drosophila_melanogaster	sturkopf	FBGN0035206
caenorhabditis_elegans		WBGENE00008693
caenorhabditis_elegans	F26A3.1	WBGENE00009140

Protein

Protein identifiers

Lipid droplet-associated hydrolase — Q9H6V9 (reviewed: Q9H6V9)

Alternative names: Lipid droplet-associated serine hydrolase

All UniProt accessions (9): Q9H6V9, A0A0A0MSH6, B4DRG3, B5MCE2, B5MCU4, B5MDU6, C9JHU6, C9JUM0, D3YTH1

UniProt curated annotations — full annotation on UniProt →

Function. Probable serine lipid hydrolase associated with lipid droplets. Has low cholesterol esterase activity. Appears to lack triglyceride lipase activity. Involved in cholesterol and triglyceride homeostasis; has opposing effects, stimulating cellular triglyceride accumulation and cellular cholesterol release. Acts antagonistically with PNPLA2/ATGL in regulation of cellular lipid stores. May regulate triglyceride accumulation indirectly through stimulation of PNPLA2/ATGL ubiquitination and proteasomal degradation. Promotes microtubule-dependent lipid droplet fusion. Highly expressed in macrophage-rich areas in atherosclerotic lesions, suggesting that it could promote cholesterol ester turnover in macrophages.

Subcellular location. Lipid droplet. Endoplasmic reticulum.

Tissue specificity. Present in macrophage-rich areas in atherosclerotic lesions (at protein level). Expressed in monocytes and monocyte-derived macrophages (at protein level).

Similarity. Belongs to the AB hydrolase superfamily. LDAH family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H6V9-1	1	yes
Q9H6V9-2	2
Q9H6V9-3	3
Q9H6V9-4	4

RefSeq proteins (7): NP_001269648, NP_001269649, NP_001269650, NP_001269651, NP_001269652, NP_001269653, NP_068744* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019363	LDAH	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF10230

Catalyzed reactions (Rhea), 1 shown:

• a cholesterol ester + H2O = cholesterol + a fatty acid + H(+) (RHEA:36403)

UniProt features (7 total): active site 3, splice variant 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6V9-F1	90.59	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 139 (nucleophile); 271 (charge relay system); 300 (charge relay system)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): GOBP_ACYLGLYCEROL_HOMEOSTASIS, MODULE_255, GOBP_STEROL_HOMEOSTASIS, XU_GH1_AUTOCRINE_TARGETS_UP, MODULE_317, GOBP_LIPID_HOMEOSTASIS, GOBP_LIPID_METABOLIC_PROCESS, AACTTT_UNKNOWN, FISCHER_DREAM_TARGETS, CUI_TCF21_TARGETS_2_DN, GOBP_LIPID_CATABOLIC_PROCESS, ATF_01, GOBP_ORGANELLE_FUSION, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS

GO Biological Process (6): lipid catabolic process (GO:0016042), lipid storage (GO:0019915), intracellular triglyceride homeostasis (GO:0035356), cholesterol homeostasis (GO:0042632), lipid droplet fusion (GO:0160077), lipid metabolic process (GO:0006629)

GO Molecular Function (3): sterol ester esterase activity (GO:0004771), lipase activity (GO:0016298), hydrolase activity (GO:0016787)

GO Cellular Component (2): endoplasmic reticulum (GO:0005783), lipid droplet (GO:0005811)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	1
catabolic process	1
nutrient storage	1
intracellular chemical homeostasis	1
triglyceride homeostasis	1
sterol homeostasis	1
lipid droplet organization	1
organelle fusion	1
primary metabolic process	1
lipase activity	1
carboxylic ester hydrolase activity	1
hydrolase activity, acting on ester bonds	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LDAH	HS1BP3	Q53T59	615
LDAH	RFX6	Q8HWS3	439
LDAH	NUDT11	Q96G61	431
LDAH	ABHD5	Q8WTS1	429
LDAH	LMTK2	Q8IWU2	417
LDAH	PNPLA2	Q96AD5	375
LDAH	MSMB	P08118	372
LDAH	FOXP4	Q8IVH2	372
LDAH	SUOX	P51687	368
LDAH	GPRC6A	Q5T6X5	355
LDAH	RINT1	Q6NUQ1	350
LDAH	EHBP1	Q8NDI1	349
LDAH	SLC22A3	O75751	348
LDAH	NCEH1	Q6PIU2	346
LDAH	AUP1	Q9Y679	344

IntAct

5 interactions, top by confidence:

A	B	Type	Score
	TMEM223	psi-mi:“MI:0914”(association)	0.350
NRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (12): C2orf43 (Affinity Capture-MS), C2orf43 (Affinity Capture-MS), C2orf43 (Affinity Capture-MS), C2orf43 (Affinity Capture-MS), C2orf43 (Proximity Label-MS), C2orf43 (Affinity Capture-RNA), C2orf43 (Affinity Capture-MS), C2orf43 (Proximity Label-MS), C2orf43 (Proximity Label-MS), C2orf43 (Affinity Capture-MS), C2orf43 (Affinity Capture-RNA), C2orf43 (Proximity Label-MS)

ESM2 similar proteins: A0A0M4FCN7, A7M6E7, A7M6E8, B4G0F3, B8BKI7, C6JS30, E0CTF3, F4JJJ3, K7K424, K7PEY4, O23617, O48780, O80437, O80738, Q0VCR6, Q0WUI9, Q1LWG4, Q2R483, Q4V9F0, Q5FVP8, Q5XF03, Q5ZJD8, Q6P342, Q6PAZ3, Q70VZ8, Q7L5N7, Q8BYI6, Q8K3K7, Q8L7M0, Q8S8S2, Q94A08, Q94AH8, Q96MH6, Q96PD7, Q9ASU1, Q9C6L5, Q9CAY3, Q9D1E8, Q9D850, Q9DCV3

Diamond homologs: Q54LL8, Q5F477, Q5HZX7, Q5R7E8, Q8BVA5, Q9H6V9, Q9W0H3, Q06522

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

59 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1500 predictions. Top by Δscore:

Variant	Effect	Δscore
2:20701567:TACCT:T	donor_loss	1.0000
2:20701568:A:C	donor_loss	1.0000
2:20701569:C:G	donor_loss	1.0000
2:20701649:TTAG:T	acceptor_gain	1.0000
2:20774808:A:AC	donor_gain	1.0000
2:20774808:ACCGG:A	donor_loss	1.0000
2:20774809:C:CA	donor_loss	1.0000
2:20774809:C:CC	donor_gain	1.0000
2:20774975:TGAAT:T	acceptor_gain	1.0000
2:20774977:AAT:A	acceptor_gain	1.0000
2:20774978:AT:A	acceptor_gain	1.0000
2:20774980:C:CC	acceptor_gain	1.0000
2:20790253:AC:A	donor_gain	1.0000
2:20790254:CC:C	donor_gain	1.0000
2:20790254:CCCT:C	donor_gain	1.0000
2:20801335:AGG:A	donor_gain	1.0000
2:20686902:T:C	donor_gain	0.9900
2:20687090:GTAAG:G	acceptor_gain	0.9900
2:20687091:TAAG:T	acceptor_gain	0.9900
2:20701573:A:AC	donor_gain	0.9900
2:20701574:C:CC	donor_gain	0.9900
2:20701648:ATTAG:A	acceptor_gain	0.9900
2:20701650:TAG:T	acceptor_gain	0.9900
2:20701653:C:CC	acceptor_gain	0.9900
2:20701653:CTA:C	acceptor_loss	0.9900
2:20701654:T:A	acceptor_loss	0.9900
2:20701659:T:C	acceptor_gain	0.9900
2:20701659:T:TC	acceptor_gain	0.9900
2:20774804:A:AC	donor_gain	0.9900
2:20774805:C:CC	donor_gain	0.9900

AlphaMissense

2146 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:20790321:A:G	W78R	0.988
2:20790321:A:T	W78R	0.988
2:20790323:A:T	V77D	0.983
2:20774863:A:G	S139P	0.982
2:20740168:C:G	R169P	0.979
2:20686975:G:C	F302L	0.972
2:20686975:G:T	F302L	0.972
2:20686977:A:G	F302L	0.972
2:20687064:A:G	W273R	0.968
2:20687064:A:T	W273R	0.968
2:20774912:G:C	F122L	0.966
2:20774912:G:T	F122L	0.966
2:20774913:A:G	F122S	0.966
2:20774914:A:G	F122L	0.966
2:20740182:A:C	F164L	0.964
2:20740182:A:T	F164L	0.964
2:20740184:A:G	F164L	0.964
2:20774921:T:A	K119N	0.964
2:20774921:T:G	K119N	0.964
2:20790310:A:C	S81R	0.964
2:20790310:A:T	S81R	0.964
2:20790312:T:G	S81R	0.964
2:20687059:A:C	C274W	0.961
2:20740180:G:T	P165Q	0.959
2:20801390:A:T	V25D	0.958
2:20774862:G:A	S139L	0.957
2:20801383:T:A	K27N	0.956
2:20801383:T:G	K27N	0.956
2:20701603:T:A	R251S	0.955
2:20701603:T:G	R251S	0.955

dbSNP variants (sampled 300 via entrez): RS1000023420 (2:20761409 T>A), RS1000025064 (2:20690957 A>G), RS1000063313 (2:20778864 C>G), RS1000070606 (2:20735054 A>C,T), RS1000078662 (2:20816760 A>G), RS1000095908 (2:20684131 C>T), RS1000108931 (2:20769407 C>A), RS1000117064 (2:20824907 A>G,T), RS1000133763 (2:20744735 A>G), RS1000140943 (2:20713825 A>T), RS1000149320 (2:20726945 C>A), RS1000169844 (2:20693862 C>A,T), RS1000202200 (2:20756771 GA>G,GAA), RS1000203753 (2:20797990 A>G,T), RS1000216055 (2:20754239 G>A,T)

Disease associations

OMIM: gene MIM:613570 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000635_13	Response to statin therapy	8.000000e-06
GCST000750_3	Prostate cancer	8.000000e-08
GCST003148_5	Prostate cancer	5.000000e-06
GCST003739_5	Esophageal adenocarcinoma	4.000000e-08
GCST003740_1	Barrett’s esophagus or Esophageal adenocarcinoma	9.000000e-11
GCST003877_12	Abdominal aortic aneurysm	1.000000e-06
GCST004278_14	Pulse pressure	6.000000e-12
GCST005748_2	Digit length ratio (right hand)	2.000000e-19
GCST005749_14	Digit length ratio (left hand)	7.000000e-18
GCST005749_15	Digit length ratio (left hand)	1.000000e-16
GCST005750_12	Digit length ratio	8.000000e-22
GCST006003_7	Triglyceride levels	1.000000e-11
GCST007096_4	Pulse pressure	2.000000e-15
GCST007097_65	Pulse pressure	4.000000e-06
GCST007097_66	Pulse pressure	3.000000e-06
GCST007267_278	Systolic blood pressure	3.000000e-09
GCST007269_65	Pulse pressure	4.000000e-22
GCST009153_5	Adverse response to chemotherapy (amenorrhea) in breast cancer	7.000000e-07
GCST010243_26	Apolipoprotein B levels	6.000000e-21
GCST010243_42	Apolipoprotein B levels	1.000000e-17
GCST010479_56	Coronary artery disease	4.000000e-09
GCST011320_39	Type 2 diabetes or prostate cancer (pleiotropy)	2.000000e-09
GCST011345_29	Triglyceride levels	5.000000e-19
GCST011348_71	High density lipoprotein cholesterol levels	1.000000e-20

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004841	digit length ratio
EFO:0004530	triglyceride measurement
EFO:0006335	systolic blood pressure
EFO:0004615	apolipoprotein B measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, decreases expression, decreases methylation, affects cotreatment	2
sodium arsenite	decreases expression, increases abundance	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Hydrogen Peroxide	affects expression, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dimethyl Sulfoxide	increases expression	1
Gallic Acid	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects expression, increases abundance	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.