GHITM

Summary

GHITM (growth hormone inducible transmembrane protein, HGNC:17281) is a protein-coding gene on chromosome 10q23.1, encoding Growth hormone-inducible transmembrane protein (Q9H3K2). Plays an important role in maintenance of mitochondrial morphology and in mediating either calcium or potassium/proton antiport.

Enables calcium:proton antiporter activity. Involved in calcium export from the mitochondrion; inner mitochondrial membrane organization; and negative regulation of release of cytochrome c from mitochondria. Located in endoplasmic reticulum membrane and mitochondrial inner membrane.

Source: NCBI Gene 27069 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 66 total
• Druggable target: yes
• MANE Select transcript: NM_014394

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17281
Approved symbol	GHITM
Name	growth hormone inducible transmembrane protein
Location	10q23.1
Locus type	gene with protein product
Status	Approved
Aliases	HSPC282, PTD010, DERP2, My021, TMBIM5, MICS1
Ensembl gene	ENSG00000165678
Ensembl biotype	protein_coding
OMIM	619205
Entrez	27069

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 31 protein_coding, 3 retained_intron

ENST00000372134, ENST00000686247, ENST00000686583, ENST00000687085, ENST00000688802, ENST00000690067, ENST00000690283, ENST00000690587, ENST00000690920, ENST00000691155, ENST00000691609, ENST00000691751, ENST00000692871, ENST00000897421, ENST00000897422, ENST00000897423, ENST00000897424, ENST00000897425, ENST00000897426, ENST00000897427, ENST00000897428, ENST00000924091, ENST00000924092, ENST00000924093, ENST00000924094, ENST00000924095, ENST00000945340, ENST00000945341, ENST00000945342, ENST00000945343, ENST00000945344, ENST00000945345, ENST00000945346, ENST00000945347

RefSeq mRNA: 1 — MANE Select: NM_014394 NM_014394

CCDS: CCDS41542

Canonical transcript exons

ENST00000372134 — 9 exons

Exon	Start	End
ENSE00001095381	84150709	84150880
ENSE00001095386	84143995	84144106
ENSE00001095388	84142655	84142754
ENSE00001095391	84150055	84150243
ENSE00001095397	84148730	84148838
ENSE00001095400	84144875	84145016
ENSE00001147594	84141462	84141629
ENSE00001336808	84152264	84153568
ENSE00001456977	84139509	84139593

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 107.0986 / max 753.4331, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105924	86.5932	1827
105923	20.5054	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.83	gold quality
male germ cell	CL:0000015	99.74	gold quality
heart right ventricle	UBERON:0002080	99.32	gold quality
left ventricle myocardium	UBERON:0006566	99.27	gold quality
ileal mucosa	UBERON:0000331	99.22	gold quality
myocardium	UBERON:0002349	99.19	gold quality
deltoid	UBERON:0001476	99.16	gold quality
tibialis anterior	UBERON:0001385	99.14	gold quality
colonic mucosa	UBERON:0000317	99.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.00	gold quality
adult organism	UBERON:0007023	98.98	gold quality
pons	UBERON:0000988	98.97	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.95	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.95	gold quality
diaphragm	UBERON:0001103	98.94	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.94	gold quality
endothelial cell	CL:0000115	98.93	gold quality
islet of Langerhans	UBERON:0000006	98.93	gold quality
medial globus pallidus	UBERON:0002477	98.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.91	gold quality
biceps brachii	UBERON:0001507	98.90	gold quality
substantia nigra pars compacta	UBERON:0001965	98.88	gold quality
right adrenal gland	UBERON:0001233	98.87	gold quality
right adrenal gland cortex	UBERON:0035827	98.86	gold quality
triceps brachii	UBERON:0001509	98.82	gold quality
cardiac ventricle	UBERON:0002082	98.82	gold quality
heart left ventricle	UBERON:0002084	98.82	gold quality
duodenum	UBERON:0002114	98.81	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	8.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting GHITM, 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-4262	100.00	73.26	3931
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Literature-anchored findings (GeneRIF, showing 4)

• MICS1 individually functions in mitochondrial morphology and cytochrome c release. (PMID:18417609)
• The tmbim5 may participate in cell death regulation by interacting with proteins of Bcl-2 family, promoting tumor metastasis, which is deduced from the evolutionary conservation of the membrane protein family containing multiple membrane spanning segments (PMID:18440869)
• These results suggest that the TMBIM family has comparable functions in the maintenance of intracellular Ca(2) homeostasis in a wide variety of tissues (PMID:25764978)
• GHITM regulates malignant phenotype and sensitivity to PD-1 blockade of renal cancer cells via Notch signalling. (PMID:38588015)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ghitm	ENSMUSG00000041028
rattus_norvegicus	Ghitm	ENSRNOG00000013961
drosophila_melanogaster	CG2076	FBGN0030263
drosophila_melanogaster	Mics1	FBGN0037506
caenorhabditis_elegans		WBGENE00019664

Paralogs (5): FAIM2 (ENSG00000135472), TMBIM1 (ENSG00000135926), TMBIM6 (ENSG00000139644), TMBIM4 (ENSG00000155957), GRINA (ENSG00000178719)

Protein

Protein identifiers

Growth hormone-inducible transmembrane protein — Q9H3K2 (reviewed: Q9H3K2)

Alternative names: Dermal papilla-derived protein 2, Mitochondrial morphology and cristae structure 1, Transmembrane BAX inhibitor motif-containing protein 5

All UniProt accessions (1): Q9H3K2

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in maintenance of mitochondrial morphology and in mediating either calcium or potassium/proton antiport. Mediates proton-dependent calcium efflux from mitochondrion. Also functions as an electroneutral mitochondrial proton/potassium exchanger. Required for the mitochondrial tubular network and cristae organization. Involved in apoptotic release of cytochrome c. Inhibits the proteolytic activity of AFG3L2, stimulating respiration and stabilizing respiratory enzymes in actively respiring mitochondria. However, when mitochondria become hyperpolarized, GHITM loses its inhibitory activity toward AFG3L2 and the now the active AFG3L2 turns first on GHITM and, if hyperpolarization persists, on other proteins of the mitochondria, leading to a broad remodeling of the mitochondrial proteome.

Subunit / interactions. Interacts with LETM1. Interacts with AFG3L2.

Subcellular location. Mitochondrion inner membrane.

Post-translational modifications. Undergoes AFG3L2-mediated proteolytic degradation, upon hyperpolarization of mitochondria.

Similarity. Belongs to the BI1 family.

RefSeq proteins (1): NP_055209* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006214	Bax_inhibitor_1-related	Family
IPR035871	GHITM	Domain

Pfam: PF01027

Catalyzed reactions (Rhea), 2 shown:

• K(+)(in) + H(+)(out) = K(+)(out) + H(+)(in) (RHEA:29467)
• Ca(2+)(in) + 2 H(+)(out) = Ca(2+)(out) + 2 H(+)(in) (RHEA:72199)

UniProt features (21 total): topological domain 8, transmembrane region 7, sequence conflict 4, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3K2-F1	77.05	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 233 (showing top): MORF_RAGE, GOBP_POTASSIUM_ION_TRANSPORT, MULLIGHAN_NPM1_SIGNATURE_3_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, JOHANSSON_BRAIN_CANCER_EARLY_VS_LATE_DN, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_MAINTENANCE_OF_LOCATION, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_ELECTRON_TRANSPORT_CHAIN

GO Biological Process (9): calcium ion transport (GO:0006816), mitochondrial calcium ion transmembrane transport (GO:0006851), apoptotic process (GO:0006915), inner mitochondrial membrane organization (GO:0007007), negative regulation of release of cytochrome c from mitochondria (GO:0090201), calcium export from the mitochondrion (GO:0099093), mitochondrial potassium ion transmembrane transport (GO:0140141), positive regulation of mitochondrial ATP synthesis coupled electron transport (GO:1905448), proton transmembrane transport (GO:1902600)

GO Molecular Function (3): calcium channel activity (GO:0005262), calcium:proton antiporter activity (GO:0015369), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), endoplasmic reticulum membrane (GO:0005789), mitochondrial membrane (GO:0031966), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle membrane	2
metal ion transport	1
calcium ion transmembrane transport	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
mitochondrial membrane organization	1
release of cytochrome c from mitochondria	1
negative regulation of organelle organization	1
regulation of release of cytochrome c from mitochondria	1
negative regulation of apoptotic signaling pathway	1
mitochondrial calcium ion transmembrane transport	1
release of sequestered calcium ion into cytosol	1
potassium ion transmembrane transport	1
positive regulation of metabolic process	1
mitochondrial ATP synthesis coupled electron transport	1
regulation of mitochondrial ATP synthesis coupled electron transport	1
monoatomic cation transmembrane transport	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
calcium:monoatomic cation antiporter activity	1
metal cation:proton antiporter activity	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
mitochondrion	1
mitochondrial envelope	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GHITM	TLR4	O00206	921
GHITM	LY96	Q9Y6Y9	910
GHITM	COPS7A	Q9UBW8	877
GHITM	MINDY3	Q9H8M7	800
GHITM	TMEM45A	Q9NWC5	787
GHITM	PDCL	Q13371	771
GHITM	TMEM9	Q9P0T7	737
GHITM	CLEC4M	Q9H2X3	676
GHITM	TMBIM1	Q969X1	640
GHITM	PEDS1	A5PLL7	596
GHITM	GRINA	Q7Z429	591
GHITM	FAIM2	Q9BWQ8	587
GHITM	CD209	Q9NNX6	584
GHITM	PDC	P20941	581
GHITM	ARL6IP5	O75915	571

IntAct

204 interactions, top by confidence:

A	B	Type	Score
BCL2	BCL2L11	psi-mi:“MI:0914”(association)	0.930
ANKLE2	PPP2R1A	psi-mi:“MI:0914”(association)	0.850
GHITM		psi-mi:“MI:0915”(physical association)	0.660
VSIG1	TTI1	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
POMK	LRP5	psi-mi:“MI:0914”(association)	0.640
LYPD3	SCAMP1	psi-mi:“MI:0914”(association)	0.640
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
CYP7B1	UBB	psi-mi:“MI:0914”(association)	0.560
GHITM	FXYD3	psi-mi:“MI:0915”(physical association)	0.560
GHITM	TMEM242	psi-mi:“MI:0915”(physical association)	0.560
JSRP1	GHITM	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	GHITM	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	GHITM	psi-mi:“MI:0915”(physical association)	0.560
FXYD3	GHITM	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	GHITM	psi-mi:“MI:0915”(physical association)	0.560
GHITM	YARS1	psi-mi:“MI:0915”(physical association)	0.560
SH3GLB1	GHITM	psi-mi:“MI:0915”(physical association)	0.560
GHITM	SPRED1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (209): GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-MS), GHITM (Affinity Capture-RNA)

ESM2 similar proteins: A0A8I3S9V6, A6NH52, A6QPI6, B1AZA5, B1H3B1, D3ZXD8, E1BD52, E1BWM5, F1N5S9, Q08DM5, Q0VCK9, Q0X0A5, Q29S14, Q3KNM2, Q3SZB3, Q3ZBL5, Q3ZC24, Q4R3C7, Q4RY26, Q58EA0, Q5BJS4, Q5R9I4, Q5R9K4, Q5RAJ8, Q5XIA8, Q5ZJ41, Q5ZJB7, Q6DH87, Q6GM44, Q6NYY9, Q6P4H8, Q75Q41, Q8IVP5, Q91VC9, Q91ZQ0, Q96GC9, Q99KU0, Q9BUV8, Q9CPQ3, Q9CQT9

Diamond homologs: O74888, P55061, P55062, Q0V882, Q54K40, Q5R7R1, Q5XIA8, Q66RM2, Q9D2C7, Q9H3K2, Q9HC24, Q9IA79, Q9KSA1, Q9LD45, Q9MBD8, Q9VSH3, P0DXN1, P0DXN2, P0DXN3, Q9ZE15, Q91VC9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GHITM	“down-regulates quantity”	CYCS	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 222 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.

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	5	17.2×	7e-03
intracellular zinc ion homeostasis	6	14.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1019 predictions. Top by Δscore:

Variant	Effect	Δscore
10:84141625:GCAGG:G	donor_gain	1.0000
10:84141628:GG:G	donor_gain	1.0000
10:84141629:GG:G	donor_gain	1.0000
10:84142644:A:AG	acceptor_gain	1.0000
10:84142644:AT:A	acceptor_gain	1.0000
10:84142644:ATGT:A	acceptor_gain	1.0000
10:84142645:T:G	acceptor_gain	1.0000
10:84142752:AAAG:A	donor_loss	1.0000
10:84142753:AAG:A	donor_loss	1.0000
10:84142755:G:C	donor_loss	1.0000
10:84142755:G:GG	donor_gain	1.0000
10:84142756:T:G	donor_loss	1.0000
10:84143983:T:TA	acceptor_gain	1.0000
10:84143985:T:TA	acceptor_gain	1.0000
10:84143990:T:A	acceptor_gain	1.0000
10:84143990:TGCA:T	acceptor_loss	1.0000
10:84143990:TGCAG:T	acceptor_gain	1.0000
10:84143991:GCA:G	acceptor_gain	1.0000
10:84143991:GCAG:G	acceptor_loss	1.0000
10:84143992:CAG:C	acceptor_gain	1.0000
10:84143992:CAGTT:C	acceptor_loss	1.0000
10:84143993:A:AG	acceptor_gain	1.0000
10:84143993:AGT:A	acceptor_gain	1.0000
10:84143993:AGTT:A	acceptor_gain	1.0000
10:84143994:G:GT	acceptor_gain	1.0000
10:84143994:GT:G	acceptor_gain	1.0000
10:84143994:GTT:G	acceptor_gain	1.0000
10:84143994:GTTG:G	acceptor_gain	1.0000
10:84143994:GTTGA:G	acceptor_gain	1.0000
10:84144102:GC:G	donor_gain	1.0000

AlphaMissense

2212 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:84150789:A:C	S288R	0.998
10:84150791:C:A	S288R	0.998
10:84150791:C:G	S288R	0.998
10:84144933:A:C	S134R	0.996
10:84144935:T:A	S134R	0.996
10:84144935:T:G	S134R	0.996
10:84150786:T:C	F287L	0.995
10:84150788:C:A	F287L	0.995
10:84150788:C:G	F287L	0.995
10:84152296:T:A	I329K	0.994
10:84144040:G:A	G92D	0.992
10:84148823:T:A	W193R	0.992
10:84148823:T:C	W193R	0.992
10:84144037:T:A	V91D	0.991
10:84150133:G:A	G224D	0.991
10:84150142:G:A	G227E	0.991
10:84150160:C:A	A233D	0.991
10:84152296:T:G	I329R	0.991
10:84144054:T:C	C97R	0.990
10:84148813:G:C	K189N	0.990
10:84148813:G:T	K189N	0.990
10:84150076:C:A	A205D	0.990
10:84150144:G:C	G228R	0.990
10:84150145:G:A	G228D	0.990
10:84144031:C:A	A89D	0.989
10:84150063:G:C	G201R	0.989
10:84150141:G:A	G227R	0.989
10:84150141:G:C	G227R	0.989
10:84150183:T:C	F241L	0.989
10:84150185:T:A	F241L	0.989

dbSNP variants (sampled 300 via entrez): RS1000443131 (10:84141368 C>A,T), RS1000807637 (10:84146054 T>G), RS1000847368 (10:84139985 G>C), RS1000942747 (10:84146269 A>G), RS1000950780 (10:84146112 G>C), RS1000981561 (10:84146457 A>G), RS1001110167 (10:84152075 A>T), RS1001279452 (10:84140181 C>T), RS1001403858 (10:84145787 A>G), RS1001559713 (10:84139964 G>C), RS1001782196 (10:84139899 G>A), RS1002204197 (10:84150980 A>T), RS1002286763 (10:84151792 T>C), RS1002448094 (10:84138697 C>A), RS1002745925 (10:84151443 C>G)

Disease associations

OMIM: gene MIM:619205 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003124_10	Mild influenza (H1N1) infection	3.000000e-10
GCST003125_5	Influenza A (H1N1) infection	4.000000e-09
GCST009303_4	Abstraction and mental flexibility	2.000000e-08
GCST009391_1797	Metabolite levels	4.000000e-06
GCST010002_293	Refractive error	1.000000e-70

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0009332	executive function measurement
EFO:0010449	3-methyladipic acid measurement
EFO:0010524	pimelic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067418 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.05	Kd	8.915	nM	CHEMBL3752910
8.05	ED50	8.915	nM	CHEMBL3752910
7.72	Kd	19.21	nM	CHEMBL5653589
7.72	ED50	19.21	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148430: Binding affinity to human GHITM incubated for 45 mins by Kinobead based pull down assay	kd	0.0089	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148430: Binding affinity to human GHITM incubated for 45 mins by Kinobead based pull down assay	kd	0.0192	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
JP8 aviation fuel	decreases expression	1
chloropicrin	affects expression	1
K 7174	increases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Antimony	decreases expression	1
Antimony Potassium Tartrate	decreases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Aspirin	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Clozapine	increases expression	1
Doxorubicin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651472	Binding	Binding affinity to human GHITM incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2XM	Abcam HEK293T GHITM KO 1	Transformed cell line	Female
CVCL_B2XN	Abcam HEK293T GHITM KO 2	Transformed cell line	Female
CVCL_SP98	HAP1 GHITM (-) 1	Cancer cell line	Male
CVCL_SP99	HAP1 GHITM (-) 2	Cancer cell line	Male
CVCL_SQ00	HAP1 GHITM (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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