LIPM

Summary

LIPM (lipase family member M, HGNC:23455) is a protein-coding gene on chromosome 10q23.31, encoding Lipase member M (Q5VYY2). Plays a highly specific role in the last step of keratinocyte differentiation.

Predicted to enable lipase activity. Predicted to be involved in lipid metabolic process. Predicted to be located in extracellular region.

Source: NCBI Gene 340654 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 45 total
• GTEx eGene: eQTL in 2 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.24 (unconstrained)
• MANE Select transcript: NM_001128215

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23455
Approved symbol	LIPM
Name	lipase family member M
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	bA304I5.1
Ensembl gene	ENSG00000173239
Ensembl biotype	protein_coding
OMIM	613923
Entrez	340654

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

MANE Select: ENST00000404743

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1

ENST00000404743, ENST00000539337

RefSeq mRNA: 1 — MANE Select: NM_001128215 NM_001128215

CCDS: CCDS44457

Canonical transcript exons

ENST00000404743 — 9 exons

Exon	Start	End
ENSE00001006983	88808298	88808415
ENSE00001097597	88816816	88816887
ENSE00001097600	88817825	88817896
ENSE00001097602	88815357	88815503
ENSE00001097605	88814530	88814639
ENSE00001097611	88815088	88815224
ENSE00001551500	88802730	88803043
ENSE00002522684	88813097	88813295
ENSE00003903572	88820232	88820546

Expression profiles

Bgee: expression breadth broad, 39 present calls, max score 85.94.

Highest expression (Bgee): skin of leg, zone of skin, skin of abdomen, primordial germ cell in gonad, body of stomach.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LIPM is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 2 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

4 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	3.2e-10	-0.33	10:88805642:G:T
Skin Sun Exposed Lower leg	eqtl	2.8e-06	+0.10	10:88793294:A:G
Skin Not Sun Exposed Suprapubic	eqtl	7.8e-06	+0.13	10:88793294:A:G
Skin Not Sun Exposed Suprapubic	sqtl	2.0e-03	+0.37	10:88805749:G:A

Top tissues by expression

showing 100 of 107 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	85.94	gold quality
zone of skin	UBERON:0000014	85.68	gold quality
skin of abdomen	UBERON:0001416	85.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	50.41	silver quality
body of stomach	UBERON:0001161	46.66	gold quality
granulocyte	CL:0000094	45.60	silver quality
stomach	UBERON:0000945	44.10	gold quality
lower esophagus mucosa	UBERON:0035834	43.70	silver quality
blood	UBERON:0000178	42.66	gold quality
vermiform appendix	UBERON:0001154	42.60	gold quality
colonic epithelium	UBERON:0000397	42.55	gold quality
fundus of stomach	UBERON:0001160	40.46	gold quality
rectum	UBERON:0001052	39.43	silver quality
mucosa of transverse colon	UBERON:0004991	38.47	silver quality
bone marrow cell	CL:0002092	38.37	gold quality
bone marrow	UBERON:0002371	38.05	gold quality
skeletal muscle tissue	UBERON:0001134	37.38	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle tissue	UBERON:0002385	35.22	gold quality
monocyte	CL:0000576	34.29	gold quality
body of pancreas	UBERON:0001150	33.51	gold quality
vagina	UBERON:0000996	33.49	gold quality
lymph node	UBERON:0000029	33.02	gold quality
omental fat pad	UBERON:0010414	32.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
multicellular organism	UBERON:0000468	31.69	gold quality
pancreas	UBERON:0001264	31.63	silver quality
gall bladder	UBERON:0002110	31.55	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
tonsil	UBERON:0002372	30.58	gold quality
muscle of leg	UBERON:0001383	30.46	gold quality
gastrocnemius	UBERON:0001388	30.29	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
placenta	UBERON:0001987	29.28	gold quality
prefrontal cortex	UBERON:0000451	29.20	gold quality
adult mammalian kidney	UBERON:0000082	29.03	gold quality
ectocervix	UBERON:0012249	28.77	silver quality
endometrium	UBERON:0001295	28.67	gold quality
kidney	UBERON:0002113	28.56	gold quality
adipose tissue	UBERON:0001013	28.50	gold quality
right atrium auricular region	UBERON:0006631	28.23	gold quality
duodenum	UBERON:0002114	28.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.94	silver quality
smooth muscle tissue	UBERON:0001135	27.93	gold quality
upper lobe of left lung	UBERON:0008952	27.79	silver quality
right coronary artery	UBERON:0001625	27.34	gold quality
heart	UBERON:0000948	27.21	silver quality
lung	UBERON:0002048	27.03	silver quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
tibial artery	UBERON:0007610	26.47	gold quality
popliteal artery	UBERON:0002250	26.41	gold quality
saliva-secreting gland	UBERON:0001044	26.27	gold quality
minor salivary gland	UBERON:0001830	25.98	gold quality
right lung	UBERON:0002167	25.77	gold quality
cortex of kidney	UBERON:0001225	25.67	gold quality
metanephros cortex	UBERON:0010533	25.52	gold quality
ascending aorta	UBERON:0001496	25.44	silver quality
subcutaneous adipose tissue	UBERON:0002190	25.37	gold quality
thoracic aorta	UBERON:0001515	25.19	silver quality
descending thoracic aorta	UBERON:0002345	24.73	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
hypothalamus	UBERON:0001898	24.60	silver quality
myometrium	UBERON:0001296	24.57	gold quality
small intestine	UBERON:0002108	24.23	gold quality
left coronary artery	UBERON:0001626	24.22	gold quality
prostate gland	UBERON:0002367	24.21	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	23.72	gold quality
small intestine Peyer’s patch	UBERON:0003454	23.10	gold quality
calcaneal tendon	UBERON:0003701	23.08	gold quality
muscle layer of sigmoid colon	UBERON:0035805	23.05	gold quality
right adrenal gland	UBERON:0001233	22.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	22.82	gold quality
right lobe of thyroid gland	UBERON:0001119	22.71	silver quality
adrenal gland	UBERON:0002369	22.69	gold quality
putamen	UBERON:0001874	22.66	gold quality
caudate nucleus	UBERON:0001873	22.18	gold quality
body of uterus	UBERON:0009853	22.18	gold quality
cerebellum	UBERON:0002037	21.92	gold quality
ovary	UBERON:0000992	21.91	gold quality
tibial nerve	UBERON:0001323	21.87	gold quality
cerebellar cortex	UBERON:0002129	21.85	gold quality
cerebellar hemisphere	UBERON:0002245	21.72	gold quality
left adrenal gland	UBERON:0001234	21.68	gold quality
right adrenal gland cortex	UBERON:0035827	21.66	gold quality
nucleus accumbens	UBERON:0001882	21.61	gold quality
temporal lobe	UBERON:0001871	21.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	21.55	gold quality
amygdala	UBERON:0001876	21.41	gold quality
adrenal tissue	UBERON:0018303	21.40	gold quality
thoracic mammary gland	UBERON:0005200	21.19	gold quality
adenohypophysis	UBERON:0002196	21.09	gold quality
left ovary	UBERON:0002119	20.92	gold quality
right ovary	UBERON:0002118	20.77	gold quality
left adrenal gland cortex	UBERON:0035825	20.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	20.51	gold quality
apex of heart	UBERON:0002098	20.28	gold quality
pituitary gland	UBERON:0000007	20.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.43

HPA expression

RNA tissue specificity: Tissue enriched

34 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Skin 1	tissue	26.5
Spinal cord	tissue	2.1
Breast	tissue	1.8
Pons	tissue	1.6
Midbrain	tissue	1.6
Periaqueductal gray	tissue	1.6
Medulla oblongata	tissue	1.5
Thalamus	tissue	1.5
Substantia nigra	tissue	1.5
Putamen	tissue	1.4
Superior colliculi	tissue	1.4
Prefrontal cortex	tissue	1.3
Cerebral cortex	tissue	1.3
Motor cortex	tissue	1.3
Hippocampal formation	tissue	1.3
Insular cortex	tissue	1.3
Basal ganglia	tissue	1.2
Entorhinal cortex	tissue	1.2
Retrosplenial and cingulate cortex	tissue	1.1
Septum	tissue	1.1
Temporal cortex	tissue	1.1
Amygdala	tissue	1.0
Hypothalamus	tissue	1.0
Ventral forebrain	tissue	1.0
Somatosensory cortex	tissue	1.0
Occipital cortex	tissue	1.0
Retrosplenial cortex	tissue	0.9
Cerebellum	tissue	0.8
Corpus callosum	tissue	0.8
Olfactory bulb	tissue	0.8
Vagina	tissue	0.1
Skeletal muscle	tissue	0.1
Bone marrow	tissue	0.1
Appendix	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 19; highest nTPM — Ventral spinal cord (2.1), Dorsal spinal cord (1.5), Dorsal hippocampus (1.3), Subiculum (1.2), Ventral hippocampus (1.2).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 2.11e-09, LOEUF 1.24, missense Z 0.26 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000404743 — one region, missense o/e 1.01.

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lipm	ENSMUSG00000056078
rattus_norvegicus	Lipm	ENSRNOG00000019301
drosophila_melanogaster	Lip3	FBGN0023495
drosophila_melanogaster	Lip1	FBGN0023496
drosophila_melanogaster	Lip2	FBGN0024740
drosophila_melanogaster	CG2772	FBGN0031533
drosophila_melanogaster	Lip4	FBGN0032264
drosophila_melanogaster	CG18301	FBGN0032265
drosophila_melanogaster	CG18302	FBGN0032266
drosophila_melanogaster	CG7329	FBGN0032271
drosophila_melanogaster	CG3635	FBGN0032981
drosophila_melanogaster	CG8093	FBGN0033999
drosophila_melanogaster	CG11406	FBGN0034990
drosophila_melanogaster	mag	FBGN0036996
drosophila_melanogaster	CG11598	FBGN0038067
drosophila_melanogaster	CG11600	FBGN0038068
drosophila_melanogaster	CG11608	FBGN0038069
drosophila_melanogaster	CG6753	FBGN0038070
drosophila_melanogaster	CG18530	FBGN0042207
drosophila_melanogaster	CG18284	FBGN0043825
drosophila_melanogaster	CG31089	FBGN0051089
drosophila_melanogaster	CG31091	FBGN0051091
drosophila_melanogaster	CG31871	FBGN0051871
drosophila_melanogaster	CG31872	FBGN0051872
drosophila_melanogaster	CG17097	FBGN0265264
caenorhabditis_elegans		WBGENE00009773
caenorhabditis_elegans		WBGENE00010062
caenorhabditis_elegans		WBGENE00020016
caenorhabditis_elegans		WBGENE00021963
caenorhabditis_elegans		WBGENE00022642

Paralogs (5): LIPA (ENSG00000107798), LIPF (ENSG00000182333), LIPN (ENSG00000204020), LIPK (ENSG00000204021), LIPJ (ENSG00000204022)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1926003) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased locomotor activity	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q4R4S5	98.0%	Diamond
Canis lupus familiaris	P80035	85.4%	Diamond
Bos taurus	Q29458	73.1%	Diamond
Crotalus adamanteus	J3SDX8	67.4%	Diamond
Mesocricetus auratus	Q3YBN2	50.7%	Diamond
Schizosaccharomyces pombe 972h-	O74430	50.1%	Diamond
Saccharomyces cerevisiae S288C	P34163	50.0%	Diamond
Arabidopsis thaliana	Q71DJ5	38.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ANKRD22	protein-coding	118932
LIPK	protein-coding	643414
LIPN	protein-coding	643418
ACTA2-AS1	ncRNA	100132116
STAMBPL1	protein-coding	57559
ACTA2	protein-coding	59
FAS-AS1	ncRNA	100302740
FAS	protein-coding	355

Protein

Protein identifiers

Lipase member M — Q5VYY2 (reviewed: Q5VYY2)

Alternative names: Lipase-like abhydrolase domain-containing protein 3

All UniProt accessions (1): Q5VYY2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a highly specific role in the last step of keratinocyte differentiation. May have an essential function in lipid metabolism of the most differentiated epidermal layers.

Subcellular location. Secreted.

Tissue specificity. Exclusively expressed in the epidermis within the granular keratinocytes.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VYY2-1	1	yes
Q5VYY2-2	2

RefSeq proteins (1): NP_001121687* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR025483	Lipase_euk	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF00561

UniProt features (11 total): active site 3, sequence variant 2, signal peptide 1, chain 1, domain 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VYY2-F1	88.92	0.71

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at transcript level

Subcellular location (HPA, imaging): endoplasmic reticulum

Antibody reliability (HPA): IF approved

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)

Position	Role
186	nucleophile
357	charge relay system
386	charge relay system

Disulfide bonds (1)

Type	Positions
Disulfide bond	260–269

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	48

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-6809371	Formation of the cornified envelope	curated
R-HSA-1266738	Developmental Biology	—
R-HSA-6805567	Keratinization	—

MSigDB gene sets: 27 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_LIPID_METABOLIC_PROCESS, GOBP_KERATINIZATION, GOBP_LIPID_CATABOLIC_PROCESS, GOBP_SKIN_DEVELOPMENT, GOMF_TRIACYLGLYCEROL_LIPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_CARBOXYLIC_ESTER_HYDROLASE_ACTIVITY, GOMF_LIPASE_ACTIVITY, chr10q23, GOBP_CORNIFICATION, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE

GO Biological Process (3): lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042), cornification (GO:0070268)

GO Molecular Function (5): lipoprotein lipase activity (GO:0004465), lipase activity (GO:0016298), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Keratinization	1
Developmental Biology	1

GO top-level categories

11 GO namespaces:

Category	Terms
hydrolase activity, acting on ester bonds	2
primary metabolic process	1
lipid metabolic process	1
catabolic process	1
programmed cell death	1
keratinization	1
cornified envelope assembly	1
triacylglycerol lipase activity	1
catalytic activity	1
hydrolase activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 15 of 860 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIPM	ANKRD22	Q5VYY1	643
LIPM	LIPG	Q9Y5X9	498
LIPM	RBM12	Q9NTZ6	459
LIPM	ACER1	Q8TDN7	458
LIPM	LIPC	P11150	404
LIPM	STAMBPL1	Q96FJ0	388
LIPM	TFEB	P19484	382
LIPM	SPRR4	Q96PI1	378
LIPM	KRTAP15-1	Q3LI76	372
LIPM	TGM5	O43548	370
LIPM	ARHGEF25	Q86VW2	370
LIPM	MYSM1	Q5VVJ2	367
LIPM	KRTAP3-1	Q9BYR8	363
LIPM	SCGB1D2	O95969	359
LIPM	KRT80	Q6KB66	357

IntAct

Human interaction partners of LIPM in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
CNOT8	physical association	0.000	1

BioGRID (1 interactions; top human partners by supporting records): LIPA (Negative Genetic)

Disease & clinical

Genetic variants

Variant evidence for LIPM: 45 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 42 predictions of 775):

Position(s)	Effect	Δscore	Sites
10:88813095–88813096	acceptor_loss	1.0000	6
10:88813277	donor_gain	1.0000
10:88815086–88815087	acceptor_loss	1.0000	6
10:88803044–88803045	donor_loss	0.9900	6
10:88812919	acceptor_gain	0.9900
10:88813296–88813297	donor_loss	0.9900	5
10:88815225–88815226	donor_loss	0.9900	6
10:88816888–88816889	donor_loss	0.9900	5
10:88817897–88817898	donor_loss	0.9900	5
10:88808356	donor_gain	0.9800

AlphaMissense

580 missense substitutions predicted likely pathogenic (of 2,825 scored), across 180 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D357	8	0.905	0.964
D163	8	0.901	0.937
D388	8	0.872	0.933
D69	8	0.829	0.936
D126	8	0.816	0.878
H386	8	0.736	0.870
W128	7	0.936	0.985
F151	7	0.917	0.986
W352	7	0.907	0.984
F154	7	0.906	0.990
W384	7	0.880	0.968
W107	7	0.876	0.967
F118	7	0.875	0.962
R133	7	0.871	0.969
F389	7	0.847	0.971
W152	7	0.832	0.904
F196	7	0.821	0.932
F320	7	0.811	0.952
D364	7	0.764	0.891
C260	7	0.743	0.810

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:613923 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Ozone	increases abundance, increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.