ALPK2

Summary

ALPK2 (alpha kinase 2, HGNC:20565) is a protein-coding gene on chromosome 18q21.31-q21.32, encoding Alpha-protein kinase 2 (Q86TB3). Protein kinase that recognizes phosphorylation sites in which the surrounding peptides have an alpha-helical conformation.

Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Involved in several processes, including epicardium morphogenesis; heart development; and negative regulation of Wnt signaling pathway involved in heart development. Acts upstream of or within regulation of gene expression. Located in basolateral plasma membrane.

Source: NCBI Gene 115701 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 3,212 total — 5 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_052947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20565
Approved symbol	ALPK2
Name	alpha kinase 2
Location	18q21.31-q21.32
Locus type	gene with protein product
Status	Approved
Aliases	HAK
Ensembl gene	ENSG00000198796
Ensembl biotype	protein_coding
OMIM	619965
Entrez	115701

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000361673, ENST00000587399, ENST00000587842, ENST00000589204, ENST00000590642, ENST00000590662, ENST00000857519, ENST00000941323, ENST00000941324, ENST00000941325, ENST00000941326

RefSeq mRNA: 1 — MANE Select: NM_052947 NM_052947

CCDS: CCDS11966

Canonical transcript exons

ENST00000361673 — 13 exons

Exon	Start	End
ENSE00001107650	58514993	58515081
ENSE00001107652	58503931	58504148
ENSE00001144907	58481247	58482039
ENSE00001159676	58498049	58498097
ENSE00001159697	58516908	58517182
ENSE00001159703	58523806	58523841
ENSE00001159705	58523935	58524062
ENSE00001159708	58529091	58529238
ENSE00001275742	58534834	58538224
ENSE00001365668	58628764	58629091
ENSE00001609357	58607322	58607439
ENSE00001748394	58578814	58580548
ENSE00001795585	58611689	58611817

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1581 / max 475.7342, expressed in 932 samples.

FANTOM5 promoters (34 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172145	1.7012	341
172155	0.9941	329
172147	0.9428	234
172151	0.6325	275
172157	0.5837	296
172149	0.4958	219
172148	0.4147	171
172169	0.4125	85
172146	0.4071	223
172171	0.3815	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	98.74	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.02	gold quality
myocardium	UBERON:0002349	97.77	gold quality
tibialis anterior	UBERON:0001385	97.70	gold quality
deltoid	UBERON:0001476	97.54	gold quality
heart right ventricle	UBERON:0002080	97.36	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.38	gold quality
quadriceps femoris	UBERON:0001377	95.02	gold quality
vastus lateralis	UBERON:0001379	94.74	gold quality
biceps brachii	UBERON:0001507	94.51	gold quality
skeletal muscle tissue	UBERON:0001134	94.10	gold quality
cardiac atrium	UBERON:0002081	93.76	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.64	gold quality
right atrium auricular region	UBERON:0006631	93.49	gold quality
apex of heart	UBERON:0002098	92.35	gold quality
kidney epithelium	UBERON:0004819	91.82	gold quality
cardiac ventricle	UBERON:0002082	91.62	gold quality
heart left ventricle	UBERON:0002084	91.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.07	gold quality
gastrocnemius	UBERON:0001388	90.74	gold quality
muscle tissue	UBERON:0002385	90.55	gold quality
muscle of leg	UBERON:0001383	89.17	gold quality
body of tongue	UBERON:0011876	88.28	gold quality
heart	UBERON:0000948	87.19	gold quality
stromal cell of endometrium	CL:0002255	86.02	gold quality
tongue	UBERON:0001723	84.04	gold quality
metanephros cortex	UBERON:0010533	80.65	gold quality
vena cava	UBERON:0004087	79.19	silver quality
adult mammalian kidney	UBERON:0000082	79.16	gold quality
sperm	CL:0000019	78.96	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	552.95
E-GEOD-109979	yes	146.44
E-MTAB-9388	yes	11.06
E-ANND-3	yes	5.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting ALPK2, 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-4789-5P	99.98	70.76	2721
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-1266-3P	96.23	66.36	778
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-5708	90.54	64.01	66

Literature-anchored findings (GeneRIF, showing 6)

• ALPK2 is crucial for luminal apoptosis and expression of DNA repair-related genes, possibly in the transition of normal colonic crypt to adenoma. (PMID:22641666)
• Results showed that p.Q1853E variant of ALPK2, which had been accumulating in the Japanese population, induced a metastatic phenotype of colorectal tumors by disrupting ALPK2 function. (PMID:28668886)
• Knockdown of ALPK2 blocks development and progression of renal cell carcinoma. (PMID:32330508)
• A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women. (PMID:33705408)
• ALPK2 acts as tumor promotor in development of bladder cancer through targeting DEPDC1A. (PMID:34210956)
• Hsa_circ_0065217 promotes growth and metastasis of renal cancer through regulating the miR-214-3p-ALPK2 axis. (PMID:34705617)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	alpk2	ENSDARG00000079637
mus_musculus	Alpk2	ENSMUSG00000032845
rattus_norvegicus	Alpk2	ENSRNOG00000017421

Paralogs (4): ALPK1 (ENSG00000073331), EEF2K (ENSG00000103319), HSPA12B (ENSG00000132622), HSPA12A (ENSG00000165868)

Protein

Protein identifiers

Alpha-protein kinase 2 — Q86TB3 (reviewed: Q86TB3)

Alternative names: Heart alpha-protein kinase

All UniProt accessions (1): Q86TB3

UniProt curated annotations — full annotation on UniProt →

Function. Protein kinase that recognizes phosphorylation sites in which the surrounding peptides have an alpha-helical conformation. Regulates cardiac development and cardiomyocyte differentiation by negatively regulating Wnt/beta-catenin signaling.

Subcellular location. Basolateral cell membrane.

Tissue specificity. Expressed in developing cardiac tissue and cardiomyocytes (at protein level).

Similarity. Belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.

RefSeq proteins (1): NP_443179* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR004166	a-kinase_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF02816, PF07679

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (90 total): sequence variant 38, region of interest 16, compositionally biased region 15, sequence conflict 15, domain 3, disulfide bond 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86TB3-F1	40.99	0.09

Functional residue map

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

Disulfide bonds (2): 33–98, 1808–1858

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GCANCTGNY_MYOD_Q6, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, MEF2_02, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, CAGCTG_AP4_Q5, ZHAN_MULTIPLE_MYELOMA_CD1_UP, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, ROZANOV_MMP14_TARGETS_UP, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_DN

GO Biological Process (8): heart morphogenesis (GO:0003007), negative regulation of Wnt signaling pathway involved in heart development (GO:0003308), regulation of gene expression (GO:0010468), establishment of cell polarity (GO:0030010), regulation of apoptotic process (GO:0042981), cardiac muscle cell development (GO:0055013), epicardium morphogenesis (GO:1905223), protein phosphorylation (GO:0006468)

GO Molecular Function (5): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): basolateral plasma membrane (GO:0016323), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
heart development	1
animal organ morphogenesis	1
Wnt signaling pathway involved in heart development	1
negative regulation of Wnt signaling pathway	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
establishment or maintenance of cell polarity	1
apoptotic process	1
regulation of programmed cell death	1
striated muscle cell development	1
cardiac cell development	1
cardiac muscle cell differentiation	1
anatomical structure morphogenesis	1
phosphorylation	1
protein modification process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
basal plasma membrane	1
plasma membrane region	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALPK2	ALPK1	Q96QP1	570
ALPK2	TAFA4	Q96LR4	363
ALPK2	HHIPL2	Q6UWX4	302
ALPK2	ZNF581	Q9P0T4	302
ALPK2	PRAMEF2	O60811	301
ALPK2	CD302	Q8IX05	259
ALPK2	SPHKAP	Q2M3C7	257
ALPK2	PKD1L1	Q8TDX9	253
ALPK2	DCHS2	Q6V1P9	252
ALPK2	XPO7	Q9UIA9	244
ALPK2	KIF5C	O60282	239
ALPK2	IKBKE	Q14164	238
ALPK2	NEDD4L	Q96PU5	231
ALPK2	CRTAC1	Q9NQ79	230
ALPK2	KIAA0825	Q8IV33	228

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ALPK2	H1-4	psi-mi:“MI:0915”(physical association)	0.400
ALPK2	PCNA	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
ALPK2	C2CD4B	psi-mi:“MI:0914”(association)	0.350
SYNJ2BP	EEF1E1	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): ALPK2 (Affinity Capture-RNA), ALPK2 (Synthetic Lethality), ALPK2 (Proximity Label-MS), ALPK2 (Proximity Label-MS), ALPK2 (Affinity Capture-MS), ALPK2 (Affinity Capture-MS), SPRYD3 (Affinity Capture-MS), TYW3 (Affinity Capture-MS), VAPA (Affinity Capture-MS), OBSL1 (Affinity Capture-MS), ARRB1 (Affinity Capture-MS), TRIP6 (Affinity Capture-MS), NAA10 (Affinity Capture-MS), VAPB (Affinity Capture-MS), TRIM41 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LI88, A4D1E1, D3Z987, D3ZUC6, E5FYH0, E5FYH1, E9Q3S4, F6ULY3, F7DF15, G3S077, G7H7V7, G7NY55, O35923, O54952, O88491, O95405, P38398, P48754, P51587, P97929, Q0VBV7, Q0VGT4, Q2M3C7, Q3V089, Q56UN5, Q5DTT3, Q5F2C3, Q5VWN6, Q61493, Q68DQ2, Q6J6I8, Q6J6I9, Q6J6J0, Q6NSW3, Q6ZP01, Q7TSY8, Q7Z570, Q80U44, Q864S8, Q864U1

Diamond homologs: A2AAJ9, A2ABU4, O88599, P12960, P14781, P28685, P52179, P54296, P68500, P70402, P97527, P97528, Q02173, Q07409, Q12860, Q13203, Q14896, Q28106, Q2EY15, Q2VWP7, Q2VWP9, Q589G5, Q5PQM4, Q5VTT5, Q62234, Q62682, Q63198, Q7ZW34, Q86TB3, Q91ZB0, Q924C5, Q96JA1, Q96L96, Q98936, Q9P232, B4MR28, B8VIW9, O02466, Q5WRU0, Q8QHL3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

3212 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	1993
Likely benign	1118
Benign	55

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
147283	GRCh38/hg38 18q21.2-21.32(chr18:54857756-60590631)x1	Pathogenic
1526617	GRCh37/hg19 18q21.1-23(chr18:47656799-78014123)	Pathogenic
2506541	GRCh37/hg19 18q21.31-21.32(chr18:55020078-56892966)	Pathogenic
4072093	Single allele	Pathogenic
4682934	GRCh37/hg19 18q21.2-23(chr18:53564430-74587425)x1	Pathogenic
3391825	GRCh37/hg19 18q21.31-23(chr18:56102873-74360560)x3	Likely pathogenic

SpliceAI

2890 predictions. Top by Δscore:

Variant	Effect	Δscore
18:58504123:G:T	acceptor_gain	1.0000
18:58523842:C:CC	acceptor_gain	1.0000
18:58524058:CTGCA:C	acceptor_gain	1.0000
18:58524061:CA:C	acceptor_gain	1.0000
18:58524063:C:CC	acceptor_gain	1.0000
18:58544600:A:C	donor_gain	1.0000
18:58580546:CAG:C	acceptor_gain	1.0000
18:58607320:A:AC	donor_gain	1.0000
18:58607321:C:CC	donor_gain	1.0000
18:58628760:TTACT:T	donor_loss	1.0000
18:58628762:A:AC	donor_gain	1.0000
18:58628763:C:CT	donor_gain	1.0000
18:58628763:CTTTT:C	donor_gain	1.0000
18:58498047:AC:A	donor_gain	0.9900
18:58498048:CC:C	donor_gain	0.9900
18:58504122:CGA:C	acceptor_gain	0.9900
18:58504144:TGATC:T	acceptor_gain	0.9900
18:58514991:A:AC	donor_gain	0.9900
18:58514992:C:CC	donor_gain	0.9900
18:58514992:CT:C	donor_gain	0.9900
18:58516903:CCCA:C	donor_loss	0.9900
18:58516904:CCACC:C	donor_loss	0.9900
18:58516905:CACCT:C	donor_loss	0.9900
18:58516906:A:AT	donor_loss	0.9900
18:58516907:C:A	donor_loss	0.9900
18:58516928:T:TA	donor_gain	0.9900
18:58523929:GTTTA:G	donor_loss	0.9900
18:58523930:TTTAC:T	donor_loss	0.9900
18:58523931:TTA:T	donor_loss	0.9900
18:58523932:TA:T	donor_loss	0.9900

AlphaMissense

14327 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:58481992:A:G	F2115S	0.999
18:58503931:C:G	G2083R	0.999
18:58503948:A:G	L2077P	0.999
18:58503987:A:G	F2064S	0.999
18:58504060:A:C	Y2040D	0.999
18:58504067:A:C	F2037L	0.999
18:58504067:A:T	F2037L	0.999
18:58504069:A:G	F2037L	0.999
18:58481961:G:C	C2125W	0.998
18:58481962:C:T	C2125Y	0.998
18:58481963:A:G	C2125R	0.998
18:58481991:A:C	F2115L	0.998
18:58481991:A:T	F2115L	0.998
18:58481993:A:G	F2115L	0.998
18:58498065:C:G	A2094P	0.998
18:58498073:A:T	V2091D	0.998
18:58498076:T:A	D2090V	0.998
18:58498082:A:G	L2088P	0.998
18:58503939:T:A	D2080V	0.998
18:58503951:A:G	L2076P	0.998
18:58503979:A:G	W2067R	0.998
18:58503979:A:T	W2067R	0.998
18:58515059:G:T	A1988D	0.998
18:58516987:A:G	L1954P	0.998
18:58481947:A:G	L2130P	0.997
18:58481975:A:G	C2121R	0.997
18:58481983:A:G	L2118P	0.997
18:58482028:A:G	F2103S	0.997
18:58498077:C:G	D2090H	0.997
18:58503945:A:T	V2078E	0.997

dbSNP variants (sampled 300 via entrez): RS1000001367 (18:58631089 A>AG), RS1000016844 (18:58588876 A>C), RS1000038426 (18:58504797 T>C), RS1000076968 (18:58586003 C>T), RS1000080308 (18:58538359 C>A,G), RS1000113074 (18:58562826 G>A,T), RS1000114399 (18:58621063 G>A), RS1000121173 (18:58492420 G>C), RS1000157117 (18:58543287 T>A,G), RS1000172272 (18:58512493 G>A), RS1000196579 (18:58629757 G>A), RS1000223992 (18:58570175 A>G), RS1000224183 (18:58629529 C>A,G), RS1000238230 (18:58498660 A>T), RS1000322003 (18:58619345 C>G)

Disease associations

OMIM: gene MIM:619965 | disease phenotypes: MIM:615468, MIM:147480, MIM:211600, MIM:243300

GenCC curated gene-disease

Mondo (5): combined immunodeficiency due to MALT1 deficiency (MONDO:0014197), cholestasis (MONDO:0001751), cholestasis, intrahepatic, of pregnancy, 1 (MONDO:0007829), progressive familial intrahepatic cholestasis type 1 (MONDO:0008892), benign recurrent intrahepatic cholestasis type 1 (MONDO:0009469)

Orphanet (5): Combined immunodeficiency due to MALT1 deficiency (Orphanet:397964), Benign recurrent intrahepatic cholestasis (Orphanet:65682), Intrahepatic cholestasis of pregnancy (Orphanet:69665), Progressive familial intrahepatic cholestasis type 1 (Orphanet:79306), Benign recurrent intrahepatic cholestasis type 1 (Orphanet:99960)

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001198_3	Multiple sclerosis	4.000000e-06
GCST002875_145	Diisocyanate-induced asthma	2.000000e-06
GCST007125_3	Multiple sclerosis and systolic blood pressure (pleiotropy)	8.000000e-06
GCST007320_58	Alzheimer’s disease or family history of Alzheimer’s disease	3.000000e-08
GCST007321_17	Family history of Alzheimer’s disease	2.000000e-07
GCST008162_83	Hip circumference	9.000000e-06
GCST009391_204	Metabolite levels	9.000000e-06
GCST009597_129	Multiple sclerosis	2.000000e-07
GCST009597_225	Multiple sclerosis	4.000000e-10
GCST010173_164	Triglyceride levels	2.000000e-08
GCST010241_378	Apolipoprotein A1 levels	5.000000e-10
GCST010242_320	HDL cholesterol levels	9.000000e-14
GCST010244_152	Triglyceride levels	1.000000e-11
GCST90002381_552	Eosinophil count	8.000000e-10
GCST90002381_553	Eosinophil count	1.000000e-10
GCST90002382_489	Eosinophil percentage of white cells	2.000000e-11
GCST90002382_490	Eosinophil percentage of white cells	9.000000e-12
GCST90011898_86	Alanine aminotransferase levels	2.000000e-38
GCST90011899_87	Aspartate aminotransferase levels	9.000000e-15
GCST90011900_156	Serum alkaline phosphatase levels	5.000000e-20
GCST90013406_219	Liver enzyme levels (alkaline phosphatase)	2.000000e-17

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0006335	systolic blood pressure
EFO:0009268	family history of Alzheimer’s disease
EFO:0010488	glycerol-3-phosphate measurement
EFO:0004530	triglyceride measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002779	Cholestasis	C06.130.120.135

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects cotreatment	6
Cyclosporine	increases expression, increases methylation, decreases expression	4
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	3
Estradiol	increases expression, decreases expression, affects cotreatment	3
trichostatin A	increases expression	2
sodium arsenite	decreases expression	2
perfluorooctanoic acid	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
tungsten carbide	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	increases expression	1
bisphenol A	affects cotreatment, affects methylation	1
deoxynivalenol	decreases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
o,p’-DDT	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
nickel sulfate	decreases expression	1
cupric oxide	decreases expression	1
triadimefon	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SC43	HAP1 ALPK2 (-) 1	Cancer cell line	Male
CVCL_SC44	HAP1 ALPK2 (-) 2	Cancer cell line	Male
CVCL_SC45	HAP1 ALPK2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01373918	PHASE4	TERMINATED	Low Dose Fat for the Prevention of Liver Disease in Babies With Gastrointestinal Disorders
NCT01585935	PHASE4	COMPLETED	Preventing Cholestasis Using SMOFLipid®
NCT01998620	PHASE4	UNKNOWN	Efficacy and Safety of S-adenosyl-L-methionine in Treatment of Chronic Hepatitis B Patients With Cholestasis
NCT00007020	PHASE3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT00058890	PHASE3	COMPLETED	Gabapentin to Treat Itch in Patients With Liver Disease
NCT01194063	PHASE3	COMPLETED	Use of Omegaven Fish Oil Emulsion for Parenteral Nutrition Associated Liver Disease in Infants and Children
NCT02357576	PHASE3	COMPLETED	Standard Lipid Therapy vs IVFE Minimization for Prevention of PNALD
NCT02663453	PHASE3	COMPLETED	Effectiveness of Multicomponent Lipid Emulsion in Preterm Infants Requiring Parenteral Nutrition
NCT03662282	PHASE3	COMPLETED	Omegaven as Alternative Parenteral Fat Nutrition
NCT04167358	PHASE3	ACTIVE_NOT_RECRUITING	Linerixibat Long-term Safety, and Tolerability Study
NCT04309773	PHASE3	UNKNOWN	Efficacy of 24 Month of Bezafibrate in Primary Sclerosing Cholangitis With Persistent Cholestasis Despite Ursodeoxycholic Acid Therapy
NCT03353454	PHASE3	WITHDRAWN	A Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT03566238	PHASE3	COMPLETED	This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 1 or 2
NCT03659916	PHASE3	COMPLETED	Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC
NCT03905330	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC)
NCT04185363	PHASE3	COMPLETED	An Extension Study of Maralixibat in Patients With Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT05543187	PHASE3	COMPLETED	A Study of TAK-625 for the Treatment of Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT00004315	PHASE2	UNKNOWN	Phase II Pilot Study to Compare the Bioavailability of Buffered, Enteric-Coated Ursodiol With Unmodified Ursodiol for Chronic Cholestatic Liver Disease and Cystic Fibrosis-Associated Liver Disease
NCT00080236	PHASE2	COMPLETED	Safety and Efficacy Study of a Caspase Inhibitor in Patients Undergoing Liver Transplantation
NCT00816348	PHASE2	TERMINATED	Compassionate Use of Omegaven IV Fat Emulsion
NCT00826020	PHASE2	COMPLETED	Evaluation of Omegaven™ Parenteral Nutrition in Patients With Total Parenteral Nutrition (TPN)-Induced Cholestasis
NCT00969332	PHASE2	TERMINATED	A Safety and Efficacy Study to Determine if Giving Intravenous Fish Oil Helps Children With Liver Disease
NCT01739517	PHASE2	UNKNOWN	Efficacy and Safety of Omega-3 Lipid Therapy in Pediatric Patients With Parenteral Nutrition-Associated Liver Disease
NCT02420496	PHASE2	WITHDRAWN	Enteral Fish Oil is Superior to Ursodeoxycholic Acid (UDCA) and Placebo for the Treatment of Cholestasis in Infants
NCT02966834	PHASE2	COMPLETED	Dose Response Study of GSK2330672 for the Treatment of Pruritus in Participants With Primary Biliary Cholangitis
NCT03586674	PHASE2	COMPLETED	Fibrates in Pediatric Cholestasis
NCT04604652	PHASE2	COMPLETED	Open-Label Study of HTD1801 in Adult Subjects With Primary Biliary Cholangitis
NCT02057718	PHASE2	COMPLETED	Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 (Maralixibat) in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis
NCT04729751	PHASE2	COMPLETED	A Study to Evaluate the Safety and Tolerability of Maralixibat in Infant Participants With Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS).
NCT00512629	PHASE1	COMPLETED	Cholestasis Prevention: Efficacy of IV Fish Oil
NCT01879735	PHASE1	COMPLETED	Biliary Excretion of Conjugated Bile Acids in Humans Measured by 11C-cholylsarcosine PET/CT
NCT02267707	PHASE1	TERMINATED	Pharmacokinetic and Safety Study of Nab®-Paclitaxel (ABI-007) Plus Gemcitabine in Subjects With Advanced Pancreatic Cancer Who Have Cholestatic Hyperbilirubinemia
NCT02801981	PHASE1	COMPLETED	Dose-escalation Study of GSK2330672 in Japanese Healthy Male Volunteers
NCT03992014	PHASE1	COMPLETED	Pharmacokinetics (PKs) and Metabolism of Radiolabelled Linerixibat
NCT04053023	PHASE1	COMPLETED	Linerixibat and Obeticholic Acid Drug Interaction Study in Healthy Subjects
NCT04510090	PHASE1	COMPLETED	Evaluate the Safety, Tolerability, and PK of EP547 in Healthy Subjects and Subjects With Cholestatic or Uremic Pruritus
NCT02963077	PHASE1	COMPLETED	A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384
NCT03082937	PHASE1	COMPLETED	An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects
NCT00846963	PHASE2/PHASE3	COMPLETED	Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates
NCT01247012	PHASE2/PHASE3	UNKNOWN	Minimization of IntraLipid Versus Omegaven