ACO1

Summary

ACO1 (aconitase 1, HGNC:117) is a protein-coding gene on chromosome 9p21.1, encoding Cytoplasmic aconitate hydratase (P21399). Bifunctional iron sensor that switches between 2 activities depending on iron availability.

The protein encoded by this gene is a bifunctional, cytosolic protein that functions as an essential enzyme in the TCA cycle and interacts with mRNA to control the levels of iron inside cells. When cellular iron levels are high, this protein binds to a 4Fe-4S cluster and functions as an aconitase. Aconitases are iron-sulfur proteins that function to catalyze the conversion of citrate to isocitrate. When cellular iron levels are low, the protein binds to iron-responsive elements (IREs), which are stem-loop structures found in the 5’ UTR of ferritin mRNA, and in the 3’ UTR of transferrin receptor mRNA. When the protein binds to IRE, it results in repression of translation of ferritin mRNA, and inhibition of degradation of the otherwise rapidly degraded transferrin receptor mRNA. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alternative splicing results in multiple transcript variants

Source: NCBI Gene 48 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 162 total — 2 pathogenic
• MANE Select transcript: NM_002197

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:117
Approved symbol	ACO1
Name	aconitase 1
Location	9p21.1
Locus type	gene with protein product
Status	Approved
Aliases	IRP1, IREBP
Ensembl gene	ENSG00000122729
Ensembl biotype	protein_coding
OMIM	100880
Entrez	48

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 28 protein_coding

ENST00000309951, ENST00000379923, ENST00000541043, ENST00000904450, ENST00000904451, ENST00000904452, ENST00000904453, ENST00000904454, ENST00000904455, ENST00000904456, ENST00000904457, ENST00000904458, ENST00000904459, ENST00000904460, ENST00000904461, ENST00000904462, ENST00000904463, ENST00000904464, ENST00000904465, ENST00000963206, ENST00000963207, ENST00000963208, ENST00000963209, ENST00000963210, ENST00000963211, ENST00000963212, ENST00000963213, ENST00000963214

RefSeq mRNA: 3 — MANE Select: NM_002197 NM_001278352, NM_001362840, NM_002197

CCDS: CCDS6525

Canonical transcript exons

ENST00000309951 — 21 exons

Exon	Start	End
ENSE00000832724	32418128	32418197
ENSE00000832725	32418328	32418511
ENSE00000832727	32420856	32421027
ENSE00000832728	32423319	32423419
ENSE00000832729	32424549	32424665
ENSE00000832730	32425838	32425997
ENSE00000832731	32427301	32427436
ENSE00000832732	32429419	32429503
ENSE00000832733	32430418	32430574
ENSE00000832734	32431719	32431843
ENSE00000832735	32433728	32433832
ENSE00000832736	32434559	32434701
ENSE00000832737	32436250	32436397
ENSE00000832738	32440465	32440587
ENSE00000832739	32448896	32449081
ENSE00001121894	32419038	32419177
ENSE00003704467	32449998	32454769
ENSE00003726958	32408514	32408651
ENSE00003738356	32405485	32405603
ENSE00003741859	32407261	32407429
ENSE00003843428	32384643	32384735

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 95.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.2583 / max 517.7107, expressed in 1811 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96409	40.2583	1811

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.60	gold quality
liver	UBERON:0002107	95.36	gold quality
stromal cell of endometrium	CL:0002255	95.31	gold quality
right adrenal gland	UBERON:0001233	95.26	gold quality
right adrenal gland cortex	UBERON:0035827	95.04	gold quality
adipose tissue	UBERON:0001013	94.54	gold quality
left adrenal gland	UBERON:0001234	94.50	gold quality
nephron tubule	UBERON:0001231	94.32	gold quality
adrenal cortex	UBERON:0001235	94.16	gold quality
duodenum	UBERON:0002114	94.14	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.14	gold quality
jejunal mucosa	UBERON:0000399	94.09	gold quality
adrenal gland	UBERON:0002369	94.07	gold quality
left adrenal gland cortex	UBERON:0035825	94.04	gold quality
connective tissue	UBERON:0002384	93.69	gold quality
pericardium	UBERON:0002407	93.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.08	gold quality
lower esophagus	UBERON:0013473	93.04	gold quality
adult mammalian kidney	UBERON:0000082	93.02	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.97	gold quality
body of pancreas	UBERON:0001150	92.73	gold quality
omental fat pad	UBERON:0010414	92.70	gold quality
peritoneum	UBERON:0002358	92.67	gold quality
renal medulla	UBERON:0000362	91.95	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.83	gold quality
heart left ventricle	UBERON:0002084	91.39	gold quality
adrenal tissue	UBERON:0018303	91.37	gold quality
cardiac ventricle	UBERON:0002082	91.29	gold quality
apex of heart	UBERON:0002098	91.03	gold quality
pancreas	UBERON:0001264	90.86	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	1168.17
E-MTAB-7052	yes	599.32
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MTF1, NR3C1, SP1, STAT5A

miRNA regulators (miRDB)

51 targeting ACO1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-607	99.97	73.62	5593
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-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-29A-5P	99.08	68.59	1813

Literature-anchored findings (GeneRIF, showing 4)

• identified a Twist target, T48, which acts with G protein signaling to orchestrate shape changes in the embryo; with G protein signaling, T48 recruits adherens junctions & RhoGEF2 to sites of apical constriction, ensuring changes in cell shape (PMID:17234948)
• Both genes are expressed and required for mesoderm invagination in the fruit fly Drosophila melanogaster but do not appear during mesoderm ingression of the midge Chironomus riparius. (PMID:27685537)
• Drosophila Fog/Cta and T48 pathways have overlapping and distinct contributions to mesoderm invagination. (PMID:38536475)
• Gp48 was a flavin-dependent thymidylate synthase (ThyX) that resembled the Paramecium bursaria chlorella virus-1 ThyX enzyme in its properties. (PMID:18248423)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	aco1	ENSDARG00000026376
mus_musculus	Aco1	ENSMUSG00000028405
rattus_norvegicus	Aco1	ENSRNOG00000005849

Paralogs (2): ACO2 (ENSG00000100412), IREB2 (ENSG00000136381)

Protein

Protein identifiers

Cytoplasmic aconitate hydratase — P21399 (reviewed: P21399)

Alternative names: Citrate hydro-lyase, Ferritin repressor protein, Iron regulatory protein 1, Iron-responsive element-binding protein 1

All UniProt accessions (2): P21399, V9HWB7

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional iron sensor that switches between 2 activities depending on iron availability. Iron deprivation, promotes its mRNA binding activity through which it regulates the expression of genes involved in iron uptake, sequestration and utilization. Binds to iron-responsive elements (IRES) in the untranslated region of target mRNAs preventing for instance the translation of ferritin and aminolevulinic acid synthase and stabilizing the transferrin receptor mRNA. Conversely, when cellular iron levels are high, binds a 4Fe-4S cluster which precludes RNA binding activity and promotes the aconitase activity, the isomerization of citrate to isocitrate via cis-aconitate.

Subunit / interactions. Interacts (when associated with the 4Fe-4S) with FBXL5. Interacts with frataxin(81-210).

Subcellular location. Cytoplasm. Cytosol.

Cofactor. Binds 1 [4Fe-4S] cluster per subunit.

Similarity. Belongs to the aconitase/IPM isomerase family.

RefSeq proteins (3): NP_001265281, NP_001349769, NP_002188* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000573	AconitaseA/IPMdHydase_ssu_swvl	Domain
IPR001030	Acoase/IPM_deHydtase_lsu_aba	Domain
IPR006249	Aconitase/IRP2	Family
IPR015928	Aconitase/3IPM_dehydase_swvl	Homologous_superfamily
IPR015931	Acnase/IPM_dHydase_lsu_aba_1/3	Homologous_superfamily
IPR018136	Aconitase_4Fe-4S_BS	Binding_site
IPR036008	Aconitase_4Fe-4S_dom	Homologous_superfamily
IPR044137	AcnA_IRP_Swivel	Domain

Pfam: PF00330, PF00694

Enzyme classification (BRENDA):

• EC 4.2.1.3 — aconitate hydratase (BRENDA: 53 organisms, 72 substrates, 96 inhibitors, 82 Km, 22 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CITRATE	0.12–21.1	27
ISOCITRATE	0.012–3.79	25
CIS-ACONITATE	0.0035–0.2	15
2-METHYL CIS-ACONITATE	0.0089–0.158	2
DL-ISOCITRATE	1.36–1.75	2
METHYLISOCITRATE	0.032–0.268	2
(2R,3S)-2-METHYLISOCITRATE	0.21	1

Catalyzed reactions (Rhea), 1 shown:

• citrate = D-threo-isocitrate (RHEA:10336)

UniProt features (117 total): helix 46, strand 40, binding site 9, mutagenesis site 9, turn 8, sequence variant 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2B3Y	X-RAY DIFFRACTION	1.85
2B3X	X-RAY DIFFRACTION	2.54

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21399-F1	94.75	0.88

Functional residue map

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

Ligand- & substrate-binding residues (9): 86; 205–207; 437; 503; 506; 536; 541; 699; 779–780

Post-translational modifications (1): 628

Mutagenesis-validated functional residues (9):

Position	Phenotype
300	no effect on aconitase activity or on rna binding.
437	loss of aconitase activity. leads to constitutive rna binding, irrespective of iron levels.
503	loss of aconitase activity. leads to constitutive rna binding, irrespective of iron levels.
506	loss of aconitase activity. leads to constitutive rna binding, irrespective of iron levels.
536	strongly reduced rna binding.
541	strongly reduced rna binding.
699	no effect on rna binding.
778	no effect on iron-regulated rna binding. loss of aconitase activity.
780	nearly abolishes rna binding.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-389542	NADPH regeneration
R-HSA-917937	Iron uptake and transport
R-HSA-1430728	Metabolism
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-382551	Transport of small molecules
R-HSA-8978934	Metabolism of cofactors

MSigDB gene sets: 221 (showing top): GOBP_DIGESTION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_NADPPLUS_METABOLIC_PROCESS, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_RESPONSE_TO_METAL_ION, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_TRANSLATION, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, MARTINEZ_RB1_TARGETS_UP

GO Biological Process (10): tricarboxylic acid cycle (GO:0006099), citrate metabolic process (GO:0006101), NADPH regeneration (GO:0006740), intracellular iron ion homeostasis (GO:0006879), post-embryonic development (GO:0009791), response to iron(II) ion (GO:0010040), intestinal absorption (GO:0050892), regulation of translation (GO:0006417), regulation of gene expression (GO:0010468), negative regulation of translation (GO:0017148)

GO Molecular Function (10): mRNA regulatory element binding translation repressor activity (GO:0000900), RNA binding (GO:0003723), aconitate hydratase activity (GO:0003994), iron-responsive element binding (GO:0030350), metal ion binding (GO:0046872), iron-sulfur cluster binding (GO:0051536), 3 iron, 4 sulfur cluster binding (GO:0051538), 4 iron, 4 sulfur cluster binding (GO:0051539), protein binding (GO:0005515), lyase activity (GO:0016829)

GO Cellular Component (6): cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of cofactors	1
Transport of small molecules	1
Metabolism	1
Metabolism of vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
intracellular membrane-bounded organelle	3
translation	2
mRNA binding	2
iron-sulfur cluster binding	2
cellular anatomical structure	2
endomembrane system	2
aerobic respiration	1
primary metabolic process	1
tricarboxylic acid metabolic process	1
generation of precursor metabolites and energy	1
NADP+ metabolic process	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
multicellular organism development	1
multicellular organismal process	1
response to iron ion	1
digestive system process	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
translation repressor activity	1
nucleic acid binding	1
hydro-lyase activity	1
cation binding	1
metal cluster binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

3974 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACO1	FXN	Q16595	963
ACO1	NFS1	Q9Y697	937
ACO1	ISCU	Q9H1K1	936
ACO1	SLC11A2	P49281	924
ACO1	IDH1	O75874	918
ACO1	IDH2	P48735	912
ACO1	CS	O75390	897
ACO1	FH	P07954	892
ACO1	TFRC	P02786	886
ACO1	LYRM4	Q9HD34	879
ACO1	ABCB7	O75027	869
ACO1	F5H3C5	F5H3C5	868
ACO1	SOD2	P04179	868
ACO1	MDH2	P40926	867
ACO1	FBXL5	Q9UKA1	860

IntAct

34 interactions, top by confidence:

A	B	Type	Score
LYRM4	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
ACO1	BRAF	psi-mi:“MI:0915”(physical association)	0.550
BRAF	ACO1	psi-mi:“MI:2364”(proximity)	0.550
SGCG	ACO1	psi-mi:“MI:2364”(proximity)	0.450
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
BOLA3	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
DDR1		psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350
BRSK1	ANKRD28	psi-mi:“MI:0914”(association)	0.350
SSX1	ACO1	psi-mi:“MI:0914”(association)	0.350
YBX1	NOP56	psi-mi:“MI:0914”(association)	0.350
NEB	ACO1	psi-mi:“MI:2364”(proximity)	0.270
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	ACO1	psi-mi:“MI:2364”(proximity)	0.270
ACO1	pbpG	psi-mi:“MI:0915”(physical association)	0.000
ligB	ACO1	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	ACO1	psi-mi:“MI:0915”(physical association)	0.000
ACO1	CCDC69	psi-mi:“MI:0915”(physical association)	0.000
CLTC	ACO1	psi-mi:“MI:0915”(physical association)	0.000
ACO1	CLTC	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	ACO1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (73): ACO1 (Affinity Capture-RNA), ACO1 (Affinity Capture-RNA), ACO1 (Affinity Capture-RNA), ACO1 (Affinity Capture-RNA), ACO1 (Co-fractionation), TXNDC17 (Co-fractionation), ACO1 (Affinity Capture-MS), ACO1 (Affinity Capture-MS), ACO1 (Proximity Label-MS), ACO1 (Affinity Capture-MS), ACO1 (Affinity Capture-MS), ACO1 (Affinity Capture-Western), ACO1 (Affinity Capture-MS), ACO1 (Affinity Capture-MS), ACO1 (Proximity Label-MS)

ESM2 similar proteins: A0JMA0, B0B7M4, B0BBT9, B3VKQ2, C4K3J5, O04916, O08451, O19906, O84310, P05990, P07264, P09339, P21399, P25516, P28271, P37032, P43847, P48200, P49601, P49608, P51375, P70920, Q00464, Q01059, Q0I5H4, Q0VCU1, Q1XDB2, Q23500, Q2A1K3, Q3KM54, Q42560, Q42669, Q4QME6, Q54X73, Q59938, Q5PB42, Q5ZLQ4, Q62751, Q63270, Q6NTP2

Diamond homologs: A0JMA0, A0QX20, A4YF02, A5MZ75, A7IA28, B3VKQ2, C3MKR6, C3MUB4, C3N1A2, C3N992, C3NMW1, C4KKU5, D9X0I3, D9XF46, O04916, O08451, O53166, P09339, P21399, P25516, P28271, P37032, P48200, P49608, P63433, P63434, P70920, P99148, Q01059, Q0RDK8, Q0VCU1, Q16DI8, Q1RKD5, Q23500, Q2A1K3, Q42560, Q42669, Q4JC10, Q4JVM4, Q4UK20

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKCA	down-regulates	ACO1	phosphorylation
ACO1	“down-regulates quantity”	citrate(3-)	“chemical modification”
ACO1	“up-regulates quantity”	D-threo-isocitrate(3-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	111
Likely benign	10
Benign	10

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1527487	GRCh37/hg19 9p24.3-q21.11(chr9:203861-69002883)	Pathogenic
153185	GRCh38/hg38 9p21.1-q21.11(chr9:31426827-68257015)x3	Pathogenic

SpliceAI

2668 predictions. Top by Δscore:

Variant	Effect	Δscore
9:32384732:GGAG:G	donor_gain	1.0000
9:32384733:GAG:G	donor_gain	1.0000
9:32384733:GAGG:G	donor_gain	1.0000
9:32384735:GGT:G	donor_loss	1.0000
9:32384736:G:GG	donor_gain	1.0000
9:32405480:TTCA:T	acceptor_loss	1.0000
9:32405481:TCA:T	acceptor_loss	1.0000
9:32405483:A:AG	acceptor_gain	1.0000
9:32405483:A:C	acceptor_loss	1.0000
9:32405483:AG:A	acceptor_gain	1.0000
9:32405484:G:A	acceptor_loss	1.0000
9:32405484:G:GA	acceptor_gain	1.0000
9:32405484:GG:G	acceptor_gain	1.0000
9:32405484:GGA:G	acceptor_gain	1.0000
9:32405484:GGAA:G	acceptor_gain	1.0000
9:32405484:GGAAC:G	acceptor_gain	1.0000
9:32405560:A:T	donor_gain	1.0000
9:32405599:A:G	donor_gain	1.0000
9:32405604:G:GG	donor_gain	1.0000
9:32405605:T:G	donor_loss	1.0000
9:32407422:G:GT	donor_gain	1.0000
9:32407430:G:GG	donor_gain	1.0000
9:32408508:TCTTA:T	acceptor_loss	1.0000
9:32408509:CTTA:C	acceptor_loss	1.0000
9:32408510:TTA:T	acceptor_loss	1.0000
9:32408511:TAG:T	acceptor_loss	1.0000
9:32408512:A:AG	acceptor_gain	1.0000
9:32408512:A:AT	acceptor_loss	1.0000
9:32408512:AG:A	acceptor_gain	1.0000
9:32408512:AGG:A	acceptor_gain	1.0000

AlphaMissense

5846 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:32418467:A:T	D205V	1.000
9:32425955:A:C	S436R	1.000
9:32425957:C:A	S436R	1.000
9:32425957:C:G	S436R	1.000
9:32429452:C:G	C506W	1.000
9:32430455:G:T	R536M	1.000
9:32407408:G:C	R82P	0.999
9:32408612:T:C	L122P	0.999
9:32418385:C:G	H178D	0.999
9:32418451:A:C	S200R	0.999
9:32418453:C:A	S200R	0.999
9:32418453:C:G	S200R	0.999
9:32418466:G:C	D205H	0.999
9:32418467:A:C	D205A	0.999
9:32418472:C:G	H207D	0.999
9:32419061:G:C	A228P	0.999
9:32424592:G:A	G372E	0.999
9:32425946:G:C	A433P	0.999
9:32425958:T:C	C437R	0.999
9:32425959:G:A	C437Y	0.999
9:32425960:C:G	C437W	0.999
9:32425966:C:A	N439K	0.999
9:32425966:C:G	N439K	0.999
9:32425970:A:C	S441R	0.999
9:32425972:T:A	S441R	0.999
9:32425972:T:G	S441R	0.999
9:32427360:A:C	S470R	0.999
9:32427362:C:A	S470R	0.999
9:32427362:C:G	S470R	0.999
9:32427372:G:T	G474W	0.999

dbSNP variants (sampled 300 via entrez): RS1000000383 (9:32442275 C>T), RS1000030176 (9:32442648 C>T), RS1000032785 (9:32402450 T>C), RS1000067564 (9:32392790 A>T), RS1000080429 (9:32409019 T>G), RS1000159181 (9:32419190 A>T), RS1000181542 (9:32450725 T>A), RS1000231190 (9:32384847 G>A), RS1000266083 (9:32425295 C>T), RS1000267295 (9:32415715 G>C,T), RS1000312089 (9:32437288 T>C), RS1000320631 (9:32431570 C>T), RS1000399707 (9:32428757 T>C), RS1000432977 (9:32428951 T>C), RS1000464026 (9:32422536 C>T)

Disease associations

OMIM: gene MIM:100880 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001508_3	Asthma	4.000000e-06
GCST002441_5	Immune response to measles-mumps-rubella vaccine	3.000000e-08
GCST002740_68	Inflammatory skin disease	4.000000e-09
GCST002759_3	Motion sickness	1.000000e-27
GCST004601_116	Red blood cell count	1.000000e-11
GCST004604_133	Hematocrit	3.000000e-10
GCST004615_62	Hemoglobin concentration	2.000000e-09
GCST007327_111	Smoking status (ever vs never smokers)	2.000000e-09
GCST009218_21	Lateral ventricle temporal horn volume	9.000000e-06
GCST010083_161	Hemoglobin levels	5.000000e-25
GCST010083_250	Hemoglobin levels	3.000000e-11
GCST90002383_512	Hematocrit	1.000000e-13
GCST90002383_513	Hematocrit	6.000000e-19
GCST90002384_258	Hemoglobin	2.000000e-13
GCST90002384_259	Hemoglobin	1.000000e-18
GCST90002403_607	Red blood cell count	6.000000e-11
GCST90002403_608	Red blood cell count	1.000000e-21

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0006928	motion sickness
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004318	smoking behavior

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	increases expression, affects folding, decreases activity, decreases expression, increases abundance	4
nickel chloride	increases activity, decreases activity, increases expression, increases stability, decreases reaction	3
Air Pollutants	increases expression, affects expression, decreases expression, affects cotreatment, increases abundance	3
Nickel	decreases reaction, increases activity, decreases expression	3
bisphenol A	decreases expression, decreases methylation	2
Arsenic Trioxide	decreases expression, increases expression	2
Cobalt	increases activity	2
Doxorubicin	affects response to substance, decreases expression	2
Iron	increases activity, decreases reaction	2
Ozone	increases abundance, affects expression, affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	increases expression	1
lasiocarpine	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
lead nitrate	decreases expression, decreases reaction	1
linalool	increases expression	1
ferrous sulfate	decreases reaction, increases activity, increases expression	1
tetrabromobisphenol A	decreases expression	1
ferric sulfate	decreases reaction, increases activity	1
gallium nitrate	increases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, decreases expression	1
nickel acetate	affects 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_B0YX	Abcam U2OS ACO1 KO	Cancer cell line	Female
CVCL_E5FH	U2OS PBRM1 KO 1	Cancer cell line	Female
CVCL_E5FI	U2OS PBRM1 KO 2	Cancer cell line	Female

Clinical trials (associated diseases)

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