MAP4K5

Summary

MAP4K5 (mitogen-activated protein kinase kinase kinase kinase 5, HGNC:6867) is a protein-coding gene on chromosome 14q22.1, encoding Mitogen-activated protein kinase kinase kinase kinase 5 (Q9Y4K4). May play a role in the response to environmental stress.

This gene encodes a member of the serine/threonine protein kinase family, that is highly similar to yeast SPS1/STE20 kinase. Yeast SPS1/STE20 functions near the beginning of the MAP kinase signal cascades that is essential for yeast pheromone response. This kinase was shown to activate Jun kinase in mammalian cells, which suggested a role in stress response. Two alternatively spliced transcript variants encoding the same protein have been described for this gene.

Source: NCBI Gene 11183 — RefSeq curated summary.

At a glance

• GWAS associations: 465
• Clinical variants (ClinVar): 438 total
• Phenotypes (HPO): 1
• Druggable target: yes — 67 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006575

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6867
Approved symbol	MAP4K5
Name	mitogen-activated protein kinase kinase kinase kinase 5
Location	14q22.1
Locus type	gene with protein product
Status	Approved
Aliases	KHS1, GCKR, KHS
Ensembl gene	ENSG00000012983
Ensembl biotype	protein_coding
OMIM	604923
Entrez	11183

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000013125, ENST00000554066, ENST00000554091, ENST00000554990, ENST00000555216, ENST00000557124, ENST00000557210, ENST00000557390, ENST00000557578, ENST00000682126, ENST00000872354, ENST00000937351, ENST00000937352, ENST00000945330, ENST00000945331

RefSeq mRNA: 2 — MANE Select: NM_006575 NM_006575, NM_198794

CCDS: CCDS91875

Canonical transcript exons

ENST00000682126 — 33 exons

Exon	Start	End
ENSE00000656978	50448774	50448832
ENSE00000656980	50456516	50456594
ENSE00000656981	50462665	50462781
ENSE00000854653	50531942	50532158
ENSE00002533981	50532448	50532569
ENSE00003459472	50504800	50504857
ENSE00003461203	50443729	50443770
ENSE00003474085	50464052	50464133
ENSE00003485599	50437476	50437534
ENSE00003487849	50468651	50468782
ENSE00003499430	50425907	50425977
ENSE00003512022	50445041	50445194
ENSE00003515586	50434394	50434571
ENSE00003527720	50446079	50446121
ENSE00003530283	50476259	50476306
ENSE00003533692	50482361	50482416
ENSE00003533716	50475077	50475149
ENSE00003543613	50437894	50438008
ENSE00003549604	50429192	50429260
ENSE00003552321	50440013	50440073
ENSE00003558362	50440362	50440441
ENSE00003565466	50486104	50486194
ENSE00003571042	50434962	50435065
ENSE00003580407	50485578	50485642
ENSE00003607960	50423121	50423176
ENSE00003611516	50443939	50444036
ENSE00003638948	50476128	50476170
ENSE00003657050	50447414	50447481
ENSE00003667297	50466583	50466645
ENSE00003687196	50442732	50442816
ENSE00003692052	50428662	50428754
ENSE00003917607	50418521	50420106
ENSE00003917981	50438092	50438094

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 96.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.4701 / max 302.5122, expressed in 1815 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143156	22.2839	1806
143157	6.3033	1694
143155	0.7194	394
143160	0.4750	282
143159	0.3687	212
143158	0.3198	150

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	96.60	gold quality
sural nerve	UBERON:0015488	95.47	gold quality
calcaneal tendon	UBERON:0003701	95.46	gold quality
tibia	UBERON:0000979	95.24	gold quality
esophagus squamous epithelium	UBERON:0006920	95.12	gold quality
endocervix	UBERON:0000458	94.52	gold quality
ectocervix	UBERON:0012249	94.33	gold quality
body of uterus	UBERON:0009853	93.98	gold quality
tibial nerve	UBERON:0001323	93.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.84	gold quality
germinal epithelium of ovary	UBERON:0001304	93.73	gold quality
left ovary	UBERON:0002119	93.20	gold quality
skin of abdomen	UBERON:0001416	93.11	gold quality
right ovary	UBERON:0002118	93.04	gold quality
spinal cord	UBERON:0002240	93.04	gold quality
inferior vagus X ganglion	UBERON:0005363	92.90	gold quality
epithelium of esophagus	UBERON:0001976	92.76	gold quality
skin of leg	UBERON:0001511	92.57	gold quality
myometrium	UBERON:0001296	92.47	gold quality
zone of skin	UBERON:0000014	92.38	gold quality
ovary	UBERON:0000992	92.35	gold quality
subthalamic nucleus	UBERON:0001906	92.33	gold quality
uterus	UBERON:0000995	92.31	gold quality
vagina	UBERON:0000996	92.31	gold quality
endometrium	UBERON:0001295	92.29	gold quality
visceral pleura	UBERON:0002401	92.18	gold quality
superficial temporal artery	UBERON:0001614	91.97	gold quality
skin of hip	UBERON:0001554	91.85	gold quality
colonic epithelium	UBERON:0000397	91.84	gold quality
stromal cell of endometrium	CL:0002255	91.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

157 targeting MAP4K5, 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-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-128-3P	99.95	71.17	2484

Literature-anchored findings (GeneRIF, showing 3)

• TNF signaling leads to oligomerization, ubiquitination, and activation of GCKR and activation of the SAPK pathway in a manner that depends upon TRAF2 polyubiquitination and oligomerization and Ubc13 function (PMID:12591926)
• The -822G/A polymorphism in the promoter region of the MAP4K5 gene is associated with reduced risk of type 2 diabetes in Han Chinese from Shanghai. (PMID:16699725)
• MAP4K5 expression is decreased or lost in majority of pancreatic ductal adenocarcinoma. (PMID:27023625)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	map4k5	ENSDARG00000039125
mus_musculus	Map4k5	ENSMUSG00000034761
rattus_norvegicus	Map4k5	ENSRNOG00000004923

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), STK26 (ENSG00000134602), TAOK3 (ENSG00000135090), PAK6 (ENSG00000137843), MINK1 (ENSG00000141503), PAK1 (ENSG00000149269), TAOK2 (ENSG00000149930), TNIK (ENSG00000154310), TAOK1 (ENSG00000160551), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), MAP3K19 (ENSG00000176601), PAK2 (ENSG00000180370), SBK2 (ENSG00000187550), STK39 (ENSG00000198648), STRADA (ENSG00000266173)

Protein

Protein identifiers

Mitogen-activated protein kinase kinase kinase kinase 5 — Q9Y4K4 (reviewed: Q9Y4K4)

Alternative names: Kinase homologous to SPS1/STE20, MAPK/ERK kinase kinase kinase 5

All UniProt accessions (4): Q9Y4K4, G3V4Q4, G3V4T8, G3V5C6

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.

Subunit / interactions. Interacts with both SH3 domains of the adapter proteins CRK and CRKL.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitously expressed in all tissues examined, with high levels in the ovary, testis and prostate.

Similarity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

RefSeq proteins (2): NP_006566, NP_942089 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001180	CNH_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR021160	MAPKKKK	Family
IPR050629	STE20/SPS1-PAK	Family

Pfam: PF00069, PF00780

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 (21 total): sequence variant 7, compositionally biased region 4, domain 2, binding site 2, modified residue 2, chain 1, mutagenesis site 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4K4-F1	74.15	0.40

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 (1): 140 (proton acceptor)

Ligand- & substrate-binding residues (2): 49; 26–34

Post-translational modifications (2): 335, 433

Mutagenesis-validated functional residues (1):

Position	Phenotype
49	loss of kinase activity and ability to activate jnk family.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 352 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_ACYLGLYCEROL_HOMEOSTASIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, FREAC2_01, MOOTHA_GLYCOGEN_METABOLISM, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, TGACCTY_ERR1_Q2

GO Biological Process (3): intracellular signal transduction (GO:0035556), MAPK cascade (GO:0000165), protein phosphorylation (GO:0006468)

GO Molecular Function (9): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), MAP kinase kinase kinase kinase activity (GO:0008349), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
protein kinase activity	2
cellular anatomical structure	2
signal transduction	1
intracellular signaling cassette	1
phosphorylation	1
protein modification process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
MAPK cascade	1
protein serine/threonine kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cytoplasm	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP4K5	GRB2	P29354	651
MAP4K5	CRK	P46108	611
MAP4K5	PRDX3	P30048	600
MAP4K5	UBA1	P22314	542
MAP4K5	CRKL	P46109	533
MAP4K5	PDIA6	Q15084	527
MAP4K5	MAP4K4	O95819	513
MAP4K5	HBM	Q6B0K9	477
MAP4K5	NCK2	O43639	463
MAP4K5	ILK	P57043	445
MAP4K5	DDR2	Q16832	428
MAP4K5	POC1B	Q8TC44	426
MAP4K5	SNAPC3	Q92966	418
MAP4K5	ZNF831	Q5JPB2	411
MAP4K5	TAF1D	Q9H5J8	410

IntAct

48 interactions, top by confidence:

A	B	Type	Score
MAP4K5	GRB2	psi-mi:“MI:0915”(physical association)	0.910
	RAB8A	psi-mi:“MI:0217”(phosphorylation reaction)	0.820
	RAB8A	psi-mi:“MI:0217”(phosphorylation reaction)	0.790
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
CRK	MAP4K5	psi-mi:“MI:0915”(physical association)	0.640
MAP4K5	CRK	psi-mi:“MI:0915”(physical association)	0.640
MAP4K3	MAP4K5	psi-mi:“MI:0915”(physical association)	0.560
CDRT15	CDRT15L2	psi-mi:“MI:0914”(association)	0.530
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
CRK	BCR/ABL fusion	psi-mi:“MI:0914”(association)	0.460
MAP4K5	CRKL	psi-mi:“MI:0915”(physical association)	0.400
MAP4K5	FYN	psi-mi:“MI:0915”(physical association)	0.400
MAP4K5	NCK1	psi-mi:“MI:0915”(physical association)	0.400
MAP4K5	H1-2	psi-mi:“MI:0915”(physical association)	0.400
MAP4K5	HNRNPU	psi-mi:“MI:0915”(physical association)	0.400
MAP4K3	MAP4K5	psi-mi:“MI:0915”(physical association)	0.400
	MAP4K5	psi-mi:“MI:0915”(physical association)	0.400
SETDB1	MAP4K5	psi-mi:“MI:0915”(physical association)	0.370
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
MAP4K3	ZNF423	psi-mi:“MI:0914”(association)	0.350
MAP4K5	SNRNP70	psi-mi:“MI:0914”(association)	0.350
MAD2L1	MED19	psi-mi:“MI:0914”(association)	0.350

BioGRID (127): MAP4K5 (Affinity Capture-MS), MAP4K5 (Affinity Capture-MS), MAP4K5 (Co-fractionation), MAP4K5 (Co-fractionation), MAP4K5 (Biochemical Activity), MAP4K5 (Affinity Capture-MS), MAP4K5 (Affinity Capture-MS), MAP4K5 (Affinity Capture-MS), MAP4K5 (Affinity Capture-MS), MAP4K5 (Proximity Label-MS), MAP4K5 (Affinity Capture-MS), MAP4K5 (Affinity Capture-MS), MAP4K5 (Proximity Label-MS), MAP4K5 (Proximity Label-MS), MAP4K5 (Proximity Label-MS)

ESM2 similar proteins: A0A0G2KTI4, A0A7U2QYM2, O00763, O55236, O60942, P10687, P10894, P29074, P48722, P55014, P55015, P91926, P97789, Q03330, Q07722, Q13621, Q15147, Q28BT8, Q28EX9, Q28GH3, Q29N38, Q338B9, Q4V7N2, Q59WH0, Q641F1, Q642Q1, Q66HV4, Q6DI37, Q6H8D6, Q6NY98, Q6YXZ7, Q756G9, Q7QG73, Q7SXG4, Q7ZVX6, Q7ZY60, Q8BPM2, Q8C878, Q8WZM0, Q924I2

Diamond homologs: A0A078CGE6, A0A194W8T8, A2AQW0, A2QHV0, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A7A1P0, A8XJW8, A9RVK2, A9SY39, B0LT89, B0XXN8, B5VNQ3, C4YRB7, E9Q3S4, F4HRJ4, G4N7X0, G4NDR3, H2L099, O00506, O14047, O14305, O22040, O22042, O24527, O54748, O61122, O61125, O81472, O95382, P0CY23, P0CY24, P23561, P27636, P28829

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
MAP4K5	down-regulates	GSK3B	phosphorylation
MAP4K5	“down-regulates activity”	GSK3B/Axin/APC	phosphorylation
MAP4K5	up-regulates	MAP3K1
KRAS	up-regulates	MAP4K5
CRK	“up-regulates activity”	MAP4K5	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of signaling by CBL	6	85.1×	2e-08
Downstream signal transduction	5	54.4×	3e-06
FCGR3A-mediated phagocytosis	6	32.1×	3e-06
Constitutive Signaling by Aberrant PI3K in Cancer	6	21.8×	3e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	16.6×	1e-04
PIP3 activates AKT signaling	6	11.4×	5e-04
RAF/MAP kinase cascade	5	8.7×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	43.0×	3e-05
cell surface receptor protein tyrosine kinase signaling pathway	6	26.1×	3e-05
protein autophosphorylation	5	18.2×	7e-04
positive regulation of neuron projection development	5	17.1×	8e-04
neuron migration	5	16.7×	8e-04
protein phosphorylation	6	10.2×	1e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	9.8×	4e-03
negative regulation of apoptotic process	7	6.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	286
Likely benign	72
Benign	22

Top pathogenic / likely-pathogenic (0)

SpliceAI

5006 predictions. Top by Δscore:

Variant	Effect	Δscore
14:50420102:CAACC:C	acceptor_gain	1.0000
14:50420105:CC:C	acceptor_gain	1.0000
14:50420106:CC:C	acceptor_gain	1.0000
14:50423115:TATTA:T	donor_loss	1.0000
14:50423116:ATTAC:A	donor_loss	1.0000
14:50423117:TTACC:T	donor_loss	1.0000
14:50423118:TACCT:T	donor_loss	1.0000
14:50423119:ACC:A	donor_loss	1.0000
14:50423120:C:CG	donor_loss	1.0000
14:50423120:CCTGT:C	donor_gain	1.0000
14:50423177:C:CC	acceptor_gain	1.0000
14:50423178:T:C	acceptor_loss	1.0000
14:50425973:GCATA:G	acceptor_gain	1.0000
14:50425974:CATA:C	acceptor_gain	1.0000
14:50425974:CATAC:C	acceptor_gain	1.0000
14:50425975:ATA:A	acceptor_gain	1.0000
14:50425976:TA:T	acceptor_gain	1.0000
14:50425976:TACTA:T	acceptor_loss	1.0000
14:50425977:ACTA:A	acceptor_loss	1.0000
14:50425978:C:CC	acceptor_gain	1.0000
14:50425978:CTAA:C	acceptor_loss	1.0000
14:50428755:C:CC	acceptor_gain	1.0000
14:50428756:T:C	acceptor_gain	1.0000
14:50429190:A:AC	donor_gain	1.0000
14:50429191:C:CT	donor_gain	1.0000
14:50429191:CTGT:C	donor_gain	1.0000
14:50429262:T:C	acceptor_gain	1.0000
14:50435066:C:CC	acceptor_gain	1.0000
14:50437888:TTGTA:T	donor_loss	1.0000
14:50437889:TGTAC:T	donor_loss	1.0000

AlphaMissense

5573 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:50420038:C:T	G841E	1.000
14:50420039:C:G	G841R	1.000
14:50420039:C:T	G841R	1.000
14:50420044:A:C	L839W	1.000
14:50420044:A:G	L839S	1.000
14:50420051:A:C	Y837D	1.000
14:50420053:A:G	L836P	1.000
14:50420095:A:G	L822S	1.000
14:50420098:A:T	V821D	1.000
14:50423141:G:C	F811L	1.000
14:50423141:G:T	F811L	1.000
14:50423143:A:G	F811L	1.000
14:50423168:C:A	Q802H	1.000
14:50423168:C:G	Q802H	1.000
14:50423169:T:G	Q802P	1.000
14:50425929:C:T	G792D	1.000
14:50425930:C:G	G792R	1.000
14:50425932:T:G	Q791P	1.000
14:50425938:C:A	G789V	1.000
14:50425938:C:T	G789E	1.000
14:50425939:C:A	G789W	1.000
14:50425939:C:G	G789R	1.000
14:50425939:C:T	G789R	1.000
14:50425953:G:T	A784D	1.000
14:50425956:A:C	L783W	1.000
14:50425956:A:G	L783S	1.000
14:50425961:A:C	S781R	1.000
14:50425961:A:T	S781R	1.000
14:50425963:T:G	S781R	1.000
14:50425971:A:G	L778P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002134 (14:50530761 C>T), RS1000024860 (14:50436437 G>A,C), RS1000025602 (14:50541257 AT>A), RS1000091354 (14:50510011 A>G), RS1000103052 (14:50482162 G>C), RS1000118356 (14:50493876 T>A), RS1000149203 (14:50430814 T>C,G), RS1000179873 (14:50478837 AT>A,ATT), RS1000268838 (14:50475966 T>A), RS1000287256 (14:50463603 G>C), RS1000292067 (14:50548729 C>T), RS1000321005 (14:50559887 T>G), RS1000340086 (14:50561119 C>T), RS1000345716 (14:50470175 A>C), RS1000395415 (14:50529099 A>G)

Disease associations

OMIM: gene MIM:604923 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hypertriglyceridemia (MONDO:0005347)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0002155	Hypertriglyceridemia

GWAS associations

465 associations (top):

Study	Trait	p-value
GCST000026_2	Triglycerides	9.000000e-08
GCST000131_2	LDL cholesterol	5.000000e-07
GCST000138_8	Triglycerides	3.000000e-14
GCST000139_3	Triglycerides	6.000000e-32
GCST000178_4	C-reactive protein	7.000000e-15
GCST000184_3	Waist circumference and related phenotypes	4.000000e-08
GCST000286_10	Triglycerides	2.000000e-31
GCST000289_7	Triglycerides	3.000000e-20
GCST000292_2	Metabolic traits	4.000000e-10
GCST000418_8	Uric acid levels	1.000000e-09
GCST000533_3	Lipid metabolism phenotypes	3.000000e-29
GCST000533_48	Lipid metabolism phenotypes	4.000000e-32
GCST000533_49	Lipid metabolism phenotypes	1.000000e-37
GCST000533_50	Lipid metabolism phenotypes	3.000000e-35
GCST000533_51	Lipid metabolism phenotypes	4.000000e-24
GCST000533_52	Lipid metabolism phenotypes	3.000000e-28
GCST000568_8	Fasting blood glucose	6.000000e-38
GCST000569_4	Two-hour glucose challenge	3.000000e-10
GCST000571_2	Fasting blood insulin	4.000000e-20
GCST000579_31	Cognitive performance	8.000000e-07
GCST000581_3	Urate levels	5.000000e-06
GCST000583_3	Hematological and biochemical traits	4.000000e-09
GCST000584_1	Triglycerides	1.000000e-11
GCST000649_21	Chronic kidney disease	3.000000e-14
GCST000737_3	Hypertriglyceridemia	7.000000e-09
GCST000758_2	Triglycerides	6.000000e-133
GCST000760_21	Cholesterol, total	7.000000e-27
GCST000769_3	Calcium levels	7.000000e-06
GCST000809_1	Triglycerides	2.000000e-19
GCST000818_7	Urate levels	4.000000e-17

EFO canonical traits (88, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004458	C-reactive protein measurement
EFO:0004761	uric acid measurement
EFO:0004529	lipid measurement
EFO:0004307	glucose tolerance test
EFO:0003926	neuropsychological test
EFO:0004531	urate measurement
EFO:0004574	total cholesterol measurement
EFO:0004838	calcium measurement
EFO:0000195	metabolic syndrome
EFO:0006809	docosapentaenoic acid measurement
EFO:0004725	metabolite measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004309	platelet count
EFO:0004340	body mass index
EFO:0004696	sex hormone-binding globulin measurement
EFO:0004723	coronary artery calcification
EFO:0004536	total blood protein measurement
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0005187	C-peptide measurement
EFO:0004330	coffee consumption
EFO:0006782	cups of coffee per day measurement
EFO:0006833	glucose effectiveness measurement
EFO:0007745	lactate measurement
EFO:0004713	FEV/FVC ratio
EFO:0005000	leptin measurement
EFO:0007793	BMI-adjusted leptin measurement
EFO:0007872	caffeine metabolite measurement
EFO:0007975	gondoic acid measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015228	Hypertriglyceridemia	C18.452.584.500.500.851

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4852 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

67 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 466,278 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1229517	VEMURAFENIB	4	15,704
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL180022	NERATINIB	4	9,404
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL1091644	LINSITINIB	3	1,446
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL2105728	CRENOLANIB	3
CHEMBL217092	SARACATINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL3544983	TESEVATINIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL415049	BARASERTIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — KHS subfamily

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
bosutinib	Inhibition	9.52	pIC50
RIPK1 inhibitor 22b	Inhibition	7.43	pIC50
NIK SMI1	Inhibition	7.3	pKi

Binding affinities (BindingDB)

18 measured of 18 human assays (18 total across all organisms); most potent 18 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
BMS-354825	KD	27 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
PKC-412	KD	190 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	KD	740 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide	KD	1900 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM
1-methyl-5-[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridin-4-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	KD	4500 nM

ChEMBL bioactivities

536 potent at pChembl≥5 of 548 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.75	IC50	0.177	nM	STAUROSPORINE
9.70	Ki	0.1995	nM	CHEMBL1999414
9.70	Ki	0.1995	nM	CHEMBL1996649
9.52	IC50	0.3	nM	BOSUTINIB
9.51	IC50	0.309	nM	STAUROSPORINE
9.51	IC50	0.308	nM	STAUROSPORINE
9.30	Kd	0.5	nM	BOSUTINIB
9.20	Ki	0.631	nM	CHEMBL1980995
9.19	Kd	0.65	nM	NERATINIB
9.10	Ki	0.7943	nM	CHEMBL1979773
8.90	Ki	1.259	nM	CHEMBL1986851
8.80	Ki	1.585	nM	CHEMBL1970317
8.43	Kd	3.7	nM	PELITINIB
8.40	Kd	4	nM	FORETINIB
8.40	Ki	3.981	nM	CHEMBL1981725
8.40	Ki	3.981	nM	CHEMBL379975
8.40	Ki	3.981	nM	CHEMBL1966514
8.30	Ki	5.012	nM	CHEMBL1964692
8.30	Ki	5.012	nM	CHEMBL1994669
8.30	Ki	5.012	nM	CHEMBL1090360
8.30	Ki	5.012	nM	CHEMBL1981133
8.24	Kd	5.8	nM	CHEMBL4865410
8.22	Kd	6	nM	AZD-4547
8.20	Ki	6.31	nM	CHEMBL508928
8.20	Ki	6.31	nM	CHEMBL1965988
8.20	Ki	6.31	nM	CHEMBL1979883
8.20	Ki	6.31	nM	CHEMBL371206
8.19	IC50	6.4	nM	CHEMBL4793665
8.10	Kd	8	nM	CHEMBL4462318
8.10	Ki	7.943	nM	CHEMBL1994321
8.10	Ki	7.943	nM	CHEMBL1973211
8.10	Ki	7.943	nM	PD-0166285
8.10	Ki	7.943	nM	CHEMBL1967531
8.00	IC50	10	nM	CHEMBL3770443
8.00	Kd	10	nM	PELITINIB
8.00	Ki	10	nM	CHEMBL2005828
8.00	Ki	10	nM	CENISERTIB
7.90	Ki	12.59	nM	CHEMBL2006778
7.90	Ki	12.59	nM	CHEMBL1991429
7.90	Ki	12.59	nM	CHEMBL2006715
7.89	Kd	13	nM	NERATINIB
7.89	IC50	12.9	nM	CHEMBL6190046
7.80	Kd	16	nM	BOSUTINIB
7.80	Ki	15.85	nM	DASATINIB
7.80	Ki	15.85	nM	CHEMBL1969190
7.80	Ki	15.85	nM	CHEMBL1982465
7.80	Ki	15.85	nM	CHEMBL1990885
7.80	Ki	15.85	nM	CHEMBL1981047
7.75	Kd	18	nM	STAUROSPORINE
7.70	Ki	19.95	nM	CHEMBL1974328

PubChem BioAssay actives

141 with measured affinity, of 1440 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715304: Inhibition of human KHS using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0002	uM
Bosutinib	507427: Inhibition of MAP4K5	ic50	0.0003	uM
Neratinib	625061: Binding constant for MAP4K5 kinase domain	kd	0.0006	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256565: Average Binding Constant for MAP4K5; NA=Not Active at 10 uM	kd	0.0037	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625061: Binding constant for MAP4K5 kinase domain	kd	0.0040	uM
N-[3-[5-(4-aminophenyl)-2H-pyrazolo[3,4-b]pyridine-3-carbonyl]-2,4-difluorophenyl]-1-phenylmethanesulfonamide	1753616: Binding affinity to wild-type human partial length MAP4K5 (M1 to P297 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0058	uM
N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazol-3-yl]-4-(3,5-dimethylpiperazin-1-yl)benzamide	1425055: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0060	uM
5-[2-(1-ethylpiperidin-4-yl)-1,3-thiazol-5-yl]-3-(pyridin-4-ylmethoxy)pyridin-2-amine	1679418: Inhibition of human KHS using MBP as substrate assessed as residual activity by [gamma-33P]-ATP assay relative to control	ic50	0.0064	uM
2,6-difluoro-N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]benzenesulfonamide	1573276: Binding affinity to MAP4K5 in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay	kd	0.0080	uM
8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	1280638: Inhibition of human recombinant KHS1	ic50	0.0100	uM
(9S)-9-(hydroxymethyl)-6-[1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl]-16-oxa-2,4,8,26-tetrazatetracyclo[19.3.1.13,7.010,15]hexacosa-1(25),3,5,7(26),10,12,14,21,23-nonaene-22-carbonitrile	1964771: Inhibition of KHS (unknown origin) by Kinase assay	ic50	0.0220	uM
2,5-difluoro-N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]benzenesulfonamide	1573276: Binding affinity to MAP4K5 in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay	kd	0.0240	uM
5-[[4-[[(1S)-2,2-dideuterio-1-(4-fluorophenyl)-2-hydroxyethyl]amino]-5-(1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2H-isoindol-1-one	2023058: Inhibition of N-terminal GST-tagged human full length recombinant KHS expressed in baculovirus-infected Sf9 cells using myelin basic protein as substrate by ADP-Glo kinase assay	ic50	0.0252	uM
1-[5-(4-amino-7-ethylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethoxy)phenyl]ethanone	1415179: Inhibition of recombinant full length human MAP4K5 using myelin basic protein as substrate after 40 mins in presence of [gamma-33P]-ATP by scintillation counting analysis	ic50	0.0370	uM
Sunitinib	435805: Binding constant for MAP4K5 kinase domain	kd	0.0410	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507604: Binding affinity to MAP4K5	kd	0.0430	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435805: Binding constant for MAP4K5 kinase domain	kd	0.0450	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	389057: Binding affinity to human KHS1	kd	0.0530	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425055: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0710	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625061: Binding constant for MAP4K5 kinase domain	kd	0.0790	uM
Crizotinib	625061: Binding constant for MAP4K5 kinase domain	kd	0.0790	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526151: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MAP4K5 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0870	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168212: Inhibition of human wild type KHS using Casein as substrate preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysis	ic50	0.0990	uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	625061: Binding constant for MAP4K5 kinase domain	kd	0.1000	uM
2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide	435805: Binding constant for MAP4K5 kinase domain	kd	0.1600	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625061: Binding constant for MAP4K5 kinase domain	kd	0.1900	uM
methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate	1425055: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1930	uM
3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide	1425055: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1970	uM
8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(3-fluoro-2-pyridinyl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	1895120: Inhibition of human MAP4K5 (KHS1) by radiometric PanQinase activity assay	ic50	0.2100	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625061: Binding constant for MAP4K5 kinase domain	kd	0.2300	uM
5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one	2023058: Inhibition of N-terminal GST-tagged human full length recombinant KHS expressed in baculovirus-infected Sf9 cells using myelin basic protein as substrate by ADP-Glo kinase assay	ic50	0.2319	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625061: Binding constant for MAP4K5 kinase domain	kd	0.2600	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435805: Binding constant for MAP4K5 kinase domain	kd	0.3000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435805: Binding constant for MAP4K5 kinase domain	kd	0.3500	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625061: Binding constant for MAP4K5 kinase domain	kd	0.3600	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526151: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged MAP4K5 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.3770	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625061: Binding constant for MAP4K5 kinase domain	kd	0.3900	uM
Quizartinib	507604: Binding affinity to MAP4K5	kd	0.4400	uM
Vandetanib	435805: Binding constant for MAP4K5 kinase domain	kd	0.4500	uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine	1425055: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4550	uM
6-(4-piperazin-1-ylphenyl)-3-quinolin-4-ylfuro[3,2-b]pyridine	2113176: Inhibition of human KHS using myelin basic protein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.5390	uM
Axitinib	625061: Binding constant for MAP4K5 kinase domain	kd	0.5500	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1425055: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.5510	uM
3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol	1425055: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.6140	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435805: Binding constant for MAP4K5 kinase domain	kd	0.6200	uM
1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[4-(6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-ylamino)phenyl]urea	1735611: Inhibition of recombinant human MAP4K5 using myelin basic protein as substrate incubated for 40 mins in presence of [gamma-33ATP by scintillation counting based radiometry assay	ic50	0.7110	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1425055: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.7180	uM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	435805: Binding constant for MAP4K5 kinase domain	kd	0.7800	uM
3-[(3S,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile	413586: Binding affinity to MAP4K5	kd	0.7900	uM
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	435805: Binding constant for MAP4K5 kinase domain	kd	0.8300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	affects expression, decreases expression	3
Cadmium	decreases expression, increases abundance, increases expression	2
Tretinoin	increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TL8-506	affects cotreatment, increases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cypermethrin	increases expression	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	affects methylation	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Arbutin	decreases expression	1
Arsenic	affects methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1

ChEMBL screening assays

262 unique, capped per target: 261 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017873	Binding	Binding affinity to MAP4K5	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem
CHEMBL1963810	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MAP4K5	PubChem BioAssay data set

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SW84	HAP1 MAP4K5 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00246636	PHASE4	COMPLETED	Evaluation of Efficacy and Safety of Omacor (Omega-3-acid Ethyl Esters) as Add-on Therapy in Hypertriglyceridemic Subjects Treated With Antara (Fenofibrate) Followed by an 8-week Extension
NCT00286234	PHASE4	COMPLETED	Niacin, N-3 Fatty Acids and Insulin Resistance
NCT00346697	PHASE4	COMPLETED	Omega-3 Fatty Acids for High Triglycerides in HIV-infected Patients
NCT00397358	PHASE4	WITHDRAWN	Effect of Extraneal (Icodextrin)on Triglyceride Levels in PD Patients
NCT00473655	PHASE4	COMPLETED	Effect of Rosuvastatin on Triglyceride Levels in Mexican Hypertriglyceridemic Patients
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00745407	PHASE4	COMPLETED	Effects of Fenofibrate on Adipocytokine Levels In Hypertriglyceridemic Patients
NCT00758927	PHASE4	UNKNOWN	The Effects of Omega-3 Fatty Acid (OMACOR) on the Low-density Lipoprotein (LDL) Sub-fraction in Type 2 Diabetic Patients
NCT00891293	PHASE4	COMPLETED	A Second Open-Label Extension of a Double-Blind, Parallel, Phase IV Study to Assess the Efficacy and Safety of Adjunctive Lovaza® (Formerly Known as Omacor®) Therapy in Hypertriglyceridemic Subjects Treated With Antara™
NCT00931879	PHASE4	COMPLETED	Lovaza® and Microvascular Function in Type 2 Diabetes
NCT00934219	PHASE4	UNKNOWN	Triglyceride Lowering Study
NCT01003847	PHASE4	COMPLETED	Differential Metabolic Effects of Fenofibrate and Fatty Acid
NCT01010399	PHASE4	COMPLETED	Boosted Lexiva With Lovaza Adjunctive Therapy in Hypertriglyceridemic, HIV-Infected Subjects
NCT01180764	PHASE4	WITHDRAWN	Effects of Lovaza on High Density Lipoprotein (HDL) Composition and Function in Hypertriglyceridemia
NCT01462877	PHASE4	COMPLETED	A Study to Evaluate Fenofibrate Combination With Statin in Chinese Patients With Dyslipidemic
NCT01480687	PHASE4	UNKNOWN	Fish Oil Supplementation and Vascular Function in Hypertensive Patients With Hypertriglyceridemia
NCT01527747	PHASE4	SUSPENDED	Effects of DPP-4 Inhibition on Triglycerides
NCT01569724	PHASE4	COMPLETED	Carbohydrate Metabolism Disorder Frequency in Hypertriglyceridemia Induced by Bexarotene of Cutaneous T Cell Lymphoma
NCT01625442	PHASE4	COMPLETED	Crocus Sativus (Saffron) and Berberis Vulgaris (Barberry Fruit) in Metabolic Syndrome
NCT01660932	PHASE4	COMPLETED	Vascular and Metabolic Effects of Omega-3 Fatty Acids
NCT01666041	PHASE4	COMPLETED	Vascular and Metabolic Effects of Fenofibrate/Omega vs Fenofibrate
NCT02015988	PHASE4	UNKNOWN	Simvastatin and Fenofibrate vs Simvastatin Alone in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome
NCT02926027	PHASE4	COMPLETED	Effect of Vascepa on Improving Coronary Atherosclerosis in People With High Triglycerides Taking Statin Therapy
NCT03120299	PHASE4	COMPLETED	The Effect of Omega-3 FA on Hypertriglyceridemia in Patients With T2DM(OCEAN)
NCT03342807	PHASE4	UNKNOWN	Intravenous Administration of Insulin and Plasma Exchange on Triglyceride Levels in Early Stage of Hypertriglyceridemia-induced Pancreatitis
NCT03501680	PHASE4	UNKNOWN	Intensive Insulin for Severe/Moderate Hypertriglyceridemia Pancreatitis.
NCT05487833	PHASE4	UNKNOWN	Insulin and Standard Management in Hypertriglyceridemic Acute Pancreatitis
NCT06129526	PHASE4	UNKNOWN	Study of the Efficacy and Safety of EPA in Patients With Type-2 Diabetes
NCT00092560	PHASE3	COMPLETED	Two Investigational Drugs in Patients With Mixed Hyperlipidemia (0653-036)
NCT00092573	PHASE3	COMPLETED	Study of Ezetimibe and Fenofibrate in Patients With Mixed Hyperlipidemia (0653-036)(COMPLETED)
NCT00093899	PHASE3	COMPLETED	A Study to Evaluate an Investigational Drug in Patients With Mixed Hyperlipidemia (0653A-071)(COMPLETED)
NCT00134498	PHASE3	COMPLETED	A Study Comparing The Efficacy & Safety Of Torcetrapib/Atorvastatin And Atorvastatin In Subjects With High Triglycerides
NCT00231621	PHASE3	TERMINATED	A Study on Efficacy and Safety of Topiramate in Treatment of Obese Subjects With Dyslipidemia
NCT00246701	PHASE3	COMPLETED	Evaluation of Efficacy and Safety of Combined Omacor (Omega-3-acid Ethyl Esters) and Simvastatin Therapy in Hypertriglyceridemic Subjects
NCT00435045	PHASE3	COMPLETED	Evaluation of Efficacy and Safety of Omacor, Co-Administered With Atorvastatin, in Subjects With Hypertriglyceridemia
NCT00560430	PHASE3	COMPLETED	Regulation of Inflammatory Parameters by Telmisartan in Hypertensive Patients
NCT00887653	PHASE3	COMPLETED	Changes in Lipids and Safety of Raltegravir in HIV+ Patients With Hyperlipidemia While on Current Standard Therapy
NCT00903409	PHASE3	COMPLETED	Open-Label Extension of a Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Lovaza® and Simvastatin Therapy in Hypertriglyceridemic Subjects
NCT00973271	PHASE3	WITHDRAWN	Diazoxide Choline Controlled-Release Tablet (DCCR) for Very High Triglycerides
NCT01047501	PHASE3	COMPLETED	Effect of AMR101 (Ethyl Icosapentate) on Triglyceride (Tg) Levels in Patients on Statins With High Tg Levels (≥ 200 and < 500 mg/dL)