HIGD1A

Summary

HIGD1A (HIG1 hypoxia inducible domain family member 1A, HGNC:29527) is a protein-coding gene on chromosome 3p22.1, encoding HIG1 domain family member 1A, mitochondrial (Q9Y241). Proposed subunit of cytochrome c oxidase (COX, complex IV), which is the terminal component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water.

Acts upstream of or within negative regulation of apoptotic process. Located in mitochondrion and nucleoplasm. Part of protein-containing complex.

Source: NCBI Gene 25994 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 23 total
• Druggable target: yes
• MANE Select transcript: NM_014056

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29527
Approved symbol	HIGD1A
Name	HIG1 hypoxia inducible domain family member 1A
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	HIG1, DKFZP564K247, RCF1A
Ensembl gene	ENSG00000181061
Ensembl biotype	protein_coding
OMIM	618623
Entrez	25994

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000321331, ENST00000418900, ENST00000430190, ENST00000452906, ENST00000470543, ENST00000884323, ENST00000884324, ENST00000884325, ENST00000884326, ENST00000884327, ENST00000884328, ENST00000884329, ENST00000884330, ENST00000884331, ENST00000884332, ENST00000884333, ENST00000884334, ENST00000884335, ENST00000884336, ENST00000884337, ENST00000939772, ENST00000963786, ENST00000963787

RefSeq mRNA: 3 — MANE Select: NM_014056 NM_001099668, NM_001099669, NM_014056

CCDS: CCDS43073, CCDS46806

Canonical transcript exons

ENST00000321331 — 4 exons

Exon	Start	End
ENSE00001242400	42804436	42804490
ENSE00001887800	42782908	42785320
ENSE00003766628	42794157	42794275
ENSE00003769621	42786028	42786162

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 99.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.6356 / max 775.5929, expressed in 1808 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41818	31.3482	1803
41817	0.7842	453
41819	0.3286	130
202737	0.1747	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	99.32	gold quality
mucosa of stomach	UBERON:0001199	99.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.24	gold quality
mucosa of transverse colon	UBERON:0004991	99.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.95	gold quality
anterior cingulate cortex	UBERON:0009835	98.82	gold quality
right frontal lobe	UBERON:0002810	98.68	gold quality
adrenal tissue	UBERON:0018303	98.67	gold quality
transverse colon	UBERON:0001157	98.62	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.62	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.58	gold quality
lower esophagus	UBERON:0013473	98.57	gold quality
smooth muscle tissue	UBERON:0001135	98.54	gold quality
right atrium auricular region	UBERON:0006631	98.44	gold quality
metanephros cortex	UBERON:0010533	98.42	gold quality
prefrontal cortex	UBERON:0000451	98.41	gold quality
right lobe of liver	UBERON:0001114	98.34	gold quality
islet of Langerhans	UBERON:0000006	98.24	gold quality
right coronary artery	UBERON:0001625	98.19	gold quality
popliteal artery	UBERON:0002250	98.12	gold quality
tibial artery	UBERON:0007610	98.12	gold quality
adenohypophysis	UBERON:0002196	98.10	gold quality
left coronary artery	UBERON:0001626	97.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.96	gold quality
ectocervix	UBERON:0012249	97.96	gold quality
gall bladder	UBERON:0002110	97.94	gold quality
esophagus	UBERON:0001043	97.84	gold quality
thoracic aorta	UBERON:0001515	97.82	gold quality
descending thoracic aorta	UBERON:0002345	97.82	gold quality
ascending aorta	UBERON:0001496	97.78	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	32.15
E-GEOD-125970	yes	25.74
E-GEOD-135922	yes	25.38
E-HCAD-31	yes	21.37
E-MTAB-8410	yes	19.47
E-GEOD-81608	yes	17.23
E-MTAB-9467	yes	13.72
E-MTAB-9067	yes	11.83
E-GEOD-70580	no	544.72
E-GEOD-83139	no	8.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, HR, IRF6

miRNA regulators (miRDB)

146 targeting HIGD1A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488

Literature-anchored findings (GeneRIF, showing 12)

• depletion of HIG1 increased gamma-secretase activation and enhanced hypoxia-induced mitochondrial dysfunction (PMID:22355194)
• Nuclear localization of the mitochondrial factor HIGD1A during metabolic stress. (PMID:23646141)
• Data indicate that hypoxia-induced gene domain protein-1a (Higd-1a) inhibits Optic atrophy 1 (Opa1) cleavage and is required for mitochondrial fusion by virtue of its interaction with Opa1. (PMID:23878241)
• Higd1a plays positive roles in protecting cells from oxidative stress, and reactive oxygen species could induce Higd1a expression by upregulating PGC-1a and HIF-1a expressions. (PMID:31089410)
• High Higd-1a expression is associated with proliferation of pancreatic cancer cells through a pERK/p27/pRB pathway. (PMID:31310799)
• Higd1a, or its mimic, provides therapeutic options for the treatment of mitochondrial diseases. (PMID:31914602)
• Distinct Roles of Mitochondrial HIGD1A and HIGD2A in Respiratory Complex and Supercomplex Biogenesis. (PMID:32375044)
• HIG1 domain family member 1A disrupts proliferation, migration, and invasion of colon adenocarcinoma cells. (PMID:34787061)
• HIG1 domain family member 1A is a crucial regulator of disorders associated with hypoxia. (PMID:36804467)
• HIGD1A inactivated by DNA hypermethylation promotes invasion of kidney renal clear cell carcinoma. (PMID:37086631)
• Mitochondrial HIGD1A inhibits hepatitis B virus transcription and replication through the cellular PNKD-NF-kappaB-NR2F1 nexus. (PMID:37185850)
• The function role of HIGD1A in nonalcoholic steatohepatitis from chronic hepatitis B. (PMID:38053282)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	higd1a	ENSDARG00000022303
mus_musculus	Higd1a	ENSMUSG00000038412
rattus_norvegicus	Higd1al1	ENSRNOG00000003008
rattus_norvegicus	Higd1a	ENSRNOG00000019428
drosophila_melanogaster	CG11825	FBGN0033519

Paralogs (4): HIGD1B (ENSG00000131097), HIGD2A (ENSG00000146066), HIGD2B (ENSG00000175202), HIGD1C (ENSG00000214511)

Protein

Protein identifiers

HIG1 domain family member 1A, mitochondrial — Q9Y241 (reviewed: Q9Y241)

Alternative names: Hypoxia-inducible gene 1 protein, RCF1 homolog A

All UniProt accessions (2): C9JNU6, Q9Y241

UniProt curated annotations — full annotation on UniProt →

Function. Proposed subunit of cytochrome c oxidase (COX, complex IV), which is the terminal component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water. May play a role in the assembly of respiratory supercomplexes.

Subunit / interactions. Associates with cytochrome c oxidase (COX, complex IV); proposed complex component. Also associates with respiratory chain supercomplexes.

Subcellular location. Mitochondrion membrane. Mitochondrion inner membrane.

Induction. By hypoxia.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y241-1	1	yes
Q9Y241-2	2

RefSeq proteins (3): NP_001093138, NP_001093139, NP_054775* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007667	Hypoxia_induced_domain	Domain
IPR050355	RCF1	Family

Pfam: PF04588

UniProt features (13 total): helix 3, transmembrane region 2, modified residue 2, initiator methionine 1, chain 1, strand 1, domain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2LOM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y241-F1	63.53	0.00

Functional residue map

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

Post-translational modifications (2): 2, 8

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1234158	Regulation of gene expression by Hypoxia-inducible Factor
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 184 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, TGACCTY_ERR1_Q2, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_LEVELS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_OXYGEN_LEVELS, GROSS_HYPOXIA_VIA_ELK3_DN, GROSS_HYPOXIA_VIA_HIF1A_DN

GO Biological Process (5): cellular response to glucose starvation (GO:0042149), negative regulation of apoptotic process (GO:0043066), cellular response to hypoxia (GO:0071456), negative regulation of release of cytochrome c from mitochondria (GO:0090201), mitochondrial respirasome assembly (GO:0097250)

GO Molecular Function (0):

GO Cellular Component (7): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), protein-containing complex (GO:0032991), nucleus (GO:0005634), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cellular response to hypoxia	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
cellular response to starvation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	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
mitochondrion organization	1
mitochondrial respiratory chain complex assembly	1
nuclear lumen	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
cellular_component	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

1120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIGD1A	COX5A	P20674	890
HIGD1A	COX4I1	P13073	817
HIGD1A	COX7A2L	O14548	661
HIGD1A	COXFA4	O00483	631
HIGD1A	COX4I2	Q96KJ9	618
HIGD1A	COXFA4L2	Q9NRX3	547
HIGD1A	WBP1L	Q9NX94	507
HIGD1A	COX10	Q12887	479
HIGD1A	RLF	Q13129	476
HIGD1A	COX14	Q96I36	470
HIGD1A	PET117	Q6UWS5	468
HIGD1A	ATP5MK	Q96IX5	462
HIGD1A	ROMO1	P60602	460
HIGD1A	IMMT	Q16891	459
HIGD1A	POU2AF3	A8K830	455

IntAct

65 interactions, top by confidence:

A	B	Type	Score
STAG2	RAD21	psi-mi:“MI:0914”(association)	0.970
SERPINB13	TTC4	psi-mi:“MI:0914”(association)	0.530
CCT8L2	ACSL4	psi-mi:“MI:0914”(association)	0.530
TUBA1A	TUBAL3	psi-mi:“MI:0914”(association)	0.420
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
MS4A4A	MON2	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	COX7A2L	psi-mi:“MI:0914”(association)	0.350
ATAD3A	TMEM223	psi-mi:“MI:0914”(association)	0.350
USP32		psi-mi:“MI:0914”(association)	0.350
PRKAR1A	RBFOX3	psi-mi:“MI:0914”(association)	0.350
RAC1		psi-mi:“MI:0914”(association)	0.350
ELK1	TPP1	psi-mi:“MI:0914”(association)	0.350
PAK1		psi-mi:“MI:0914”(association)	0.350
HDAC1	HIGD1C	psi-mi:“MI:0914”(association)	0.350
FAM13B	AHCYL1	psi-mi:“MI:0914”(association)	0.350
STK31	SEC61B	psi-mi:“MI:0914”(association)	0.350
TUBGCP4	SPTLC1	psi-mi:“MI:0914”(association)	0.350
IRAK1	ILVBL	psi-mi:“MI:0914”(association)	0.350
LIMK2	HAX1	psi-mi:“MI:0914”(association)	0.350
LATS2	WTIP	psi-mi:“MI:0914”(association)	0.350
KLF16		psi-mi:“MI:0914”(association)	0.350
NTRK1	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (99): HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), IPO13 (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS), HIGD1A (Affinity Capture-MS)

ESM2 similar proteins: A0A1D8PI78, A1XJK0, A1XQR6, A2RVP7, A4QNF3, O44477, O48528, P0CR88, P0CR89, P25710, P32897, P60602, P60603, P79082, P81928, P87130, P87146, Q02889, Q0MQB8, Q0MQB9, Q0MQC0, Q12328, Q2UAP8, Q38820, Q3SZV8, Q4V7T9, Q54QM0, Q5NVQ1, Q6BT35, Q6BZY4, Q6CRJ6, Q6FT37, Q6NYD1, Q75E80, Q7T2P6, Q80W89, Q86Y39, Q8HXG6, Q8IN78, Q9C1E8

Diamond homologs: A1CHC5, A1CXG2, A2QI79, A3LVL1, A4RI25, A5DHC2, A5E2M7, A6RBB3, A6SSX6, A6ZM32, A7F679, A7TFU8, A8P006, B0D4J7, B0Y606, B2WBP3, B3LLM2, B6H465, B6K2Z6, B6QHL8, B6QHL9, B8MJJ2, B8N9M0, B9WHT6, C0NUL6, C0RYW2, C1G794, C4JHR1, C4QV79, C4Y631, C4YRP9, C5DLZ7, C5DWC4, C5FSQ7, C5GDJ2, C5JIT3, C5MAV2, C5P447, C6H220, C7GT60

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

860 predictions. Top by Δscore:

Variant	Effect	Δscore
3:42786021:AACCT:A	donor_loss	1.0000
3:42786023:CCTA:C	donor_loss	1.0000
3:42786024:CTACC:C	donor_loss	1.0000
3:42786026:A:AC	donor_gain	1.0000
3:42786027:C:CA	donor_loss	1.0000
3:42786027:C:CC	donor_gain	1.0000
3:42786027:CCAA:C	donor_gain	1.0000
3:42786158:TATTC:T	acceptor_gain	1.0000
3:42786160:TTC:T	acceptor_gain	1.0000
3:42786161:TC:T	acceptor_gain	1.0000
3:42786161:TCCT:T	acceptor_loss	1.0000
3:42786162:CC:C	acceptor_gain	1.0000
3:42786162:CCTG:C	acceptor_loss	1.0000
3:42786163:C:CC	acceptor_gain	1.0000
3:42786163:C:CG	acceptor_loss	1.0000
3:42786164:T:A	acceptor_loss	1.0000
3:42786164:T:C	acceptor_loss	1.0000
3:42794150:AACTT:A	donor_loss	1.0000
3:42794151:ACTTA:A	donor_loss	1.0000
3:42794152:CT:C	donor_loss	1.0000
3:42794152:CTT:C	donor_loss	1.0000
3:42794153:TTAC:T	donor_loss	1.0000
3:42794154:T:TA	donor_loss	1.0000
3:42794155:A:AC	donor_gain	1.0000
3:42794155:A:AT	donor_loss	1.0000
3:42794155:A:C	donor_loss	1.0000
3:42794156:C:CA	donor_loss	1.0000
3:42794156:C:CC	donor_gain	1.0000
3:42794156:C:CT	donor_loss	1.0000
3:42794156:CCAA:C	donor_gain	1.0000

AlphaMissense

591 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:42786042:C:T	G73E	0.999
3:42786153:C:T	G36D	0.999
3:42786043:C:G	G73R	0.998
3:42786043:C:T	G73R	0.998
3:42786060:G:T	A67D	0.998
3:42786154:C:G	G36R	0.998
3:42786030:A:T	V77D	0.997
3:42786054:C:T	G69D	0.997
3:42786039:G:T	A74E	0.996
3:42786040:C:G	A74P	0.996
3:42786055:C:G	G69R	0.996
3:42786156:G:T	A35E	0.996
3:42786162:C:T	G33E	0.996
3:42794157:C:G	G33R	0.996
3:42794157:C:T	G33R	0.996
3:42786028:C:G	G78R	0.995
3:42786048:A:T	V71D	0.995
3:42786064:C:G	A66P	0.995
3:42786070:G:T	R64S	0.995
3:42786081:A:G	L60P	0.995
3:42786135:G:T	A42E	0.995
3:42786138:A:T	V41D	0.995
3:42786144:G:T	A39E	0.995
3:42785315:C:G	G80R	0.994
3:42786061:C:G	A67P	0.994
3:42786147:G:T	A38E	0.994
3:42794159:A:T	V32D	0.994
3:42786081:A:T	L60Q	0.993
3:42786145:C:G	A39P	0.993
3:42794183:G:T	A24D	0.993

dbSNP variants (sampled 300 via entrez): RS1000351039 (3:42802007 G>A,T), RS1000407274 (3:42803636 G>A), RS1000608613 (3:42786089 G>A), RS1000960089 (3:42803953 C>T), RS1001175236 (3:42795787 G>A), RS1001187482 (3:42793694 A>C), RS1001246024 (3:42786264 T>C), RS1001313666 (3:42787879 C>G), RS1001389968 (3:42789464 G>C), RS1001470156 (3:42793297 C>T), RS1002148391 (3:42794648 T>C), RS1002336113 (3:42788150 A>G), RS1002420254 (3:42800680 C>T), RS1002444771 (3:42803624 CT>C), RS1002682347 (3:42784195 G>A)

Disease associations

OMIM: gene MIM:618623 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_774	Obesity-related traits	2.000000e-07
GCST001762_789	Obesity-related traits	2.000000e-07
GCST002595_14	Clozapine-induced agranulocytosis	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005188	CCL11 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067148 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.29	Kd	514.2	nM	CHEMBL5653589
6.20	ED50	631.4	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148503: Binding affinity to human HIGD1A incubated for 45 mins by Kinobead based pull down assay	kd	0.5142	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	4
Air Pollutants	affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
dicrotophos	decreases expression	1
bufotalin	increases expression	1
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
jinfukang	decreases expression	1
NSC 689534	decreases expression, affects binding	1
Resveratrol	increases expression, affects cotreatment	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Arsenic	affects methylation	1
Caffeine	increases phosphorylation	1
Copper	affects binding, decreases expression	1
Dexamethasone	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, 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
CHEMBL5651545	Binding	Binding affinity to human HIGD1A 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

Clinical trials (associated diseases)

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