LIPK

Summary

LIPK (lipase family member K, HGNC:23444) is a protein-coding gene on chromosome 10q23.31, encoding Lipase member K (Q5VXJ0). Plays a highly specific role in the last step of keratinocyte differentiation.

Predicted to enable lipoprotein lipase activity. Predicted to be involved in cornification. Predicted to be located in extracellular region. Predicted to be active in intracellular membrane-bounded organelle.

Source: NCBI Gene 643414 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_001080518

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23444
Approved symbol	LIPK
Name	lipase family member K
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	bA186O14.2
Ensembl gene	ENSG00000204021
Ensembl biotype	protein_coding
OMIM	613922
Entrez	643414

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000404190

RefSeq mRNA: 2 — MANE Select: NM_001080518 NM_001080518, NM_001378091

CCDS: CCDS44455

Canonical transcript exons

ENST00000404190 — 10 exons

Exon	Start	End
ENSE00001456480	88743250	88743321
ENSE00001456482	88737635	88737781
ENSE00001456483	88732415	88732551
ENSE00001456484	88732178	88732287
ENSE00001456486	88730983	88731181
ENSE00001456487	88726795	88726912
ENSE00001558096	88752517	88752776
ENSE00001759879	88724533	88724648
ENSE00002453949	88739996	88740067
ENSE00003917154	88706249	88706320

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 81.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0713 / max 20.3556, expressed in 22 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106061	0.0713	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	81.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.30	silver quality
zone of skin	UBERON:0000014	80.26	gold quality
skin of leg	UBERON:0001511	78.80	gold quality
quadriceps femoris	UBERON:0001377	69.42	gold quality
cerebellar vermis	UBERON:0004720	67.75	silver quality
thymus	UBERON:0002370	60.26	silver quality
esophagus mucosa	UBERON:0002469	55.05	gold quality
lower esophagus mucosa	UBERON:0035834	54.54	gold quality
vagina	UBERON:0000996	50.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	47.42	gold quality
placenta	UBERON:0001987	46.65	gold quality
esophagus	UBERON:0001043	39.77	gold quality
ectocervix	UBERON:0012249	39.34	gold quality
tonsil	UBERON:0002372	37.67	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
granulocyte	CL:0000094	36.82	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	35.32	gold quality
uterine cervix	UBERON:0000002	35.13	gold quality
bone marrow	UBERON:0002371	33.10	gold quality
muscle tissue	UBERON:0002385	32.50	gold quality
leukocyte	CL:0000738	32.33	gold quality
monocyte	CL:0000576	32.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
blood	UBERON:0000178	30.54	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.29

Regulation

Is transcription factor: no

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lipk	ENSMUSG00000024771
rattus_norvegicus	Lipk	ENSRNOG00000019409
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), LIPM (ENSG00000173239), LIPF (ENSG00000182333), LIPN (ENSG00000204020), LIPJ (ENSG00000204022)

Protein

Protein identifiers

Lipase member K — Q5VXJ0 (reviewed: Q5VXJ0)

Alternative names: Lipase-like abhydrolase domain-containing protein 2

All UniProt accessions (1): Q5VXJ0

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.

RefSeq proteins (2): NP_001073987, NP_001365020 (=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, glycosylation site 2, signal peptide 1, chain 1, domain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VXJ0-F1	92.93	0.83

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): 172 (nucleophile); 343 (charge relay system); 372 (charge relay system)

Disulfide bonds (1): 246–255

Glycosylation sites (2): 271, 327

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 32 (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

Rollup of top-2 pathways:

Category	Pathways
Keratinization	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

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

1030 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIPK	ANKRD22	Q5VYY1	402
LIPK	GLYATL2	Q8WU03	382
LIPK	STAMBPL1	Q96FJ0	370
LIPK	TCAIM	Q8N3R3	364
LIPK	MYBPH	Q13203	355
LIPK	FAM177A1	Q8N128	351
LIPK	LIAS	O43766	351
LIPK	IAH1	Q2TAA2	351
LIPK	ALDH18A1	P54886	331
LIPK	NAA16	Q6N069	326
LIPK	SLC16A12	Q6ZSM3	312
LIPK	RNLS	Q5VYX0	303
LIPK	KLLN	B2CW77	303
LIPK	ATAD1	Q8NBU5	299
LIPK	PAPSS2	O95340	298

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ADAMTS17	GAS6	psi-mi:“MI:0914”(association)	0.350
LIPK	LAMC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): CTDSP1 (Affinity Capture-MS), LAMC1 (Affinity Capture-MS), ITPA (Affinity Capture-MS), SEL1L (Affinity Capture-MS), LIPK (Affinity Capture-MS), ABHD17B (Affinity Capture-MS), DCAF8 (Affinity Capture-MS)

ESM2 similar proteins: A0A2D0TC04, A6H730, A6H757, B1H1P9, B6EWW8, D2GZV9, E1BPW0, E1C1L6, F8S0Z7, J3SBP3, J3SEZ3, O14638, O35409, O75356, P06802, P07686, P0DQQ4, P11117, P15309, P15396, P20060, P20611, P20646, P22413, P24638, P24822, P49614, P58242, P70627, P97675, Q0P5F0, Q29548, Q3KQG9, Q3MI05, Q3U4B4, Q4R5N9, Q5NVF6, Q5R5M5, Q5R8C0, Q5VXJ0

Diamond homologs: J3SDX8, O16956, O46107, O46108, O61866, O74430, P04634, P07098, P34163, P38571, P78898, P80035, Q29458, Q3U4B4, Q3YBN2, Q4R4S5, Q5VXI9, Q5VXJ0, Q5VYY2, Q5W064, Q64194, Q67ZU1, Q8BM14, Q8K2A6, Q93789, Q94252, Q9CPP7, Q9Z0M5, Q07950, Q71DJ5, O60095, Q07804

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1833 predictions. Top by Δscore:

Variant	Effect	Δscore
10:88732176:A:AG	acceptor_gain	1.0000
10:88732176:AGTTT:A	acceptor_gain	1.0000
10:88732177:G:GA	acceptor_gain	1.0000
10:88732177:GTTT:G	acceptor_gain	1.0000
10:88732177:GTTTG:G	acceptor_gain	1.0000
10:88724644:ATATT:A	donor_gain	0.9900
10:88724645:TATT:T	donor_gain	0.9900
10:88724649:G:GG	donor_gain	0.9900
10:88726793:A:AG	acceptor_gain	0.9900
10:88726793:AGAGC:A	acceptor_gain	0.9900
10:88726794:G:GG	acceptor_gain	0.9900
10:88730981:A:AG	acceptor_gain	0.9900
10:88730982:G:GA	acceptor_gain	0.9900
10:88731177:TTCAG:T	donor_loss	0.9900
10:88731178:TCAG:T	donor_loss	0.9900
10:88731179:CAGGT:C	donor_loss	0.9900
10:88731180:AGG:A	donor_loss	0.9900
10:88731181:GG:G	donor_loss	0.9900
10:88731182:G:GA	donor_loss	0.9900
10:88731183:T:A	donor_loss	0.9900
10:88732172:T:TA	acceptor_gain	0.9900
10:88732174:ATAGT:A	acceptor_loss	0.9900
10:88732176:A:AC	acceptor_loss	0.9900
10:88732177:G:C	acceptor_loss	0.9900
10:88732177:GT:G	acceptor_gain	0.9900
10:88732177:GTT:G	acceptor_gain	0.9900
10:88732277:C:T	donor_gain	0.9900
10:88740488:G:T	donor_gain	0.9900
10:88751885:A:AG	acceptor_gain	0.9900
10:88752506:ATT:A	acceptor_gain	0.9900

AlphaMissense

2652 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:88731177:T:C	F140L	0.992
10:88731179:C:A	F140L	0.992
10:88731179:C:G	F140L	0.992
10:88732269:T:C	S172P	0.989
10:88752583:G:C	D343H	0.988
10:88731099:T:A	W114R	0.987
10:88731099:T:C	W114R	0.987
10:88740000:G:C	R274P	0.984
10:88731036:T:A	W93R	0.979
10:88731036:T:C	W93R	0.979
10:88752562:G:C	A336P	0.977
10:88752568:T:A	W338R	0.977
10:88752568:T:C	W338R	0.977
10:88752584:A:C	D343A	0.976
10:88752584:A:T	D343V	0.976
10:88731110:C:A	N117K	0.975
10:88731110:C:G	N117K	0.975
10:88731060:A:C	S101R	0.973
10:88731062:T:A	S101R	0.973
10:88731062:T:G	S101R	0.973
10:88739999:C:A	R274S	0.972
10:88752679:T:C	F375L	0.972
10:88752681:T:A	F375L	0.972
10:88752681:T:G	F375L	0.972
10:88752585:C:A	D343E	0.970
10:88752585:C:G	D343E	0.970
10:88752672:T:A	H372Q	0.970
10:88752672:T:G	H372Q	0.970
10:88731180:A:C	S141R	0.969
10:88732178:T:A	S141R	0.969

dbSNP variants (sampled 300 via entrez): RS1000178526 (10:88746126 A>G), RS1000206099 (10:88746394 C>T), RS1000351365 (10:88710827 C>A,T), RS1000359966 (10:88728900 G>C), RS1000390300 (10:88740631 T>C), RS1000490740 (10:88746744 C>A), RS1000498234 (10:88722432 C>T), RS1000537610 (10:88709629 C>A), RS1000544399 (10:88728388 A>C), RS1000545205 (10:88744872 C>T), RS1000604896 (10:88735139 T>C), RS1000674377 (10:88716425 T>G), RS1000887803 (10:88751177 G>A), RS1000935760 (10:88722405 A>G), RS1001008769 (10:88722189 G>A,C)

Disease associations

OMIM: gene MIM:613922 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011109_5	Psoriasis	1.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenate	increases abundance, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Polystyrenes	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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