HPX

Summary

HPX (hemopexin, HGNC:5171) is a protein-coding gene on chromosome 11p15.4, encoding Hemopexin (P02790). Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation.

This gene encodes a plasma glycoprotein that binds heme with high affinity. The encoded protein is an acute phase protein that transports heme from the plasma to the liver and may be involved in protecting cells from oxidative stress.

Source: NCBI Gene 3263 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_000613

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5171
Approved symbol	HPX
Name	hemopexin
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000110169
Ensembl biotype	protein_coding
OMIM	142290
Entrez	3263

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 32 protein_coding, 6 protein_coding_CDS_not_defined, 5 retained_intron

ENST00000265983, ENST00000525057, ENST00000527105, ENST00000527556, ENST00000528348, ENST00000529037, ENST00000529775, ENST00000533369, ENST00000533561, ENST00000533856, ENST00000534429, ENST00000534800, ENST00000868745, ENST00000868746, ENST00000868747, ENST00000868748, ENST00000868749, ENST00000868750, ENST00000868751, ENST00000868752, ENST00000868753, ENST00000868754, ENST00000868755, ENST00000868756, ENST00000868757, ENST00000868758, ENST00000868759, ENST00000868760, ENST00000868761, ENST00000868762, ENST00000868763, ENST00000868764, ENST00000868765, ENST00000868766, ENST00000868767, ENST00000868768, ENST00000868769, ENST00000868770, ENST00000868771, ENST00000868772, ENST00000868773, ENST00000868774, ENST00000868775

RefSeq mRNA: 1 — MANE Select: NM_000613 NM_000613

CCDS: CCDS7763

Canonical transcript exons

ENST00000265983 — 10 exons

Exon	Start	End
ENSE00000903312	6437440	6437652
ENSE00000903313	6438356	6438509
ENSE00001297131	6440881	6440987
ENSE00001322887	6431049	6431470
ENSE00003467250	6431641	6431803
ENSE00003546181	6431887	6432017
ENSE00003562567	6440165	6440286
ENSE00003569929	6437046	6437177
ENSE00003661045	6440672	6440730
ENSE00003671109	6440467	6440538

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 99.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 19.6695 / max 10345.8140, expressed in 120 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118424	19.1899	94
118425	0.1691	21
118422	0.1545	27
118426	0.1048	16
118423	0.0263	7
118427	0.0196	6
118428	0.0052	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.89	gold quality
liver	UBERON:0002107	99.83	gold quality
right uterine tube	UBERON:0001302	87.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.58	gold quality
cerebellar hemisphere	UBERON:0002245	84.10	gold quality
cerebellar cortex	UBERON:0002129	83.84	gold quality
type B pancreatic cell	CL:0000169	81.96	gold quality
olfactory bulb	UBERON:0002264	81.80	gold quality
cerebellum	UBERON:0002037	81.24	gold quality
right coronary artery	UBERON:0001625	79.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.85	gold quality
cortical plate	UBERON:0005343	78.05	gold quality
descending thoracic aorta	UBERON:0002345	77.54	gold quality
tibial nerve	UBERON:0001323	77.43	gold quality
mucosa of transverse colon	UBERON:0004991	77.35	gold quality
skin of leg	UBERON:0001511	76.77	gold quality
left ventricle myocardium	UBERON:0006566	76.58	gold quality
tibial artery	UBERON:0007610	76.41	gold quality
minor salivary gland	UBERON:0001830	76.38	gold quality
popliteal artery	UBERON:0002250	76.38	gold quality
right ovary	UBERON:0002118	76.25	gold quality
body of pancreas	UBERON:0001150	75.98	gold quality
cardiac muscle of right atrium	UBERON:0003379	75.86	gold quality
skin of abdomen	UBERON:0001416	75.70	gold quality
transverse colon	UBERON:0001157	75.63	gold quality
diaphragm	UBERON:0001103	75.30	gold quality
aorta	UBERON:0000947	75.09	gold quality
body of uterus	UBERON:0009853	74.50	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	5136.72
E-HCAD-9	yes	3342.76
E-MTAB-10553	yes	2907.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, NR2F2

miRNA regulators (miRDB)

14 targeting HPX, 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-3120-5P	100.00	65.56	965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-3928-3P	97.61	66.53	1096
HSA-MIR-4749-3P	96.40	66.24	798

Literature-anchored findings (GeneRIF, showing 36)

• mesangial hemopexin is able to affect glomerular anionic sites, it is conceivable that stimulated mesangium may contribute to enhanced glomerular permeability in corticosteroid responsive nephrotic syndrome through local hemopexin release. (PMID:12675843)
• The conserved binding ability of the Hemopexin domains suggests that CD44 may act as a core molecule assembling multiple Membrane-type 1 matrix metalloproteinases on the cell surface. (PMID:15558018)
• The ability of hemopexin to bind metal ions raises the possibility that this protein may participate in the transport of metal ions in blood or in the exchange of metal ions between proteins. (PMID:15697212)
• Thermal denaturation of the human hemopexin-heme complex is investigated under a variety of solution conditions to identify factors that influence heme release, including the potential presence of transition metal ions or heme iron reduction. (PMID:15697213)
• hemopexin molecule as such can potentially act as a toxic protease, leading to proteinuria and glomerular alterations (PMID:16014037)
• Hemopexin in minimal change nephropathy relapse subjects may exist in an altered isoform, showing enhanced protease activity as compared with subjects in remission, subjects with other forms of primary glomerulopathy, or healthy controls. (PMID:16079987)
• Hemopexin and hemopexin domains of human proteins fulfill functions in activation of MMPs, inhibition of MMPs, dimerization, binding of substrates or ligands, cleavage of substrates, and endocytosis by LRP-1 and LRP-2. (PMID:17185359)
• HPX-heme(II)-NO appears to act as an efficient scavenger of peroxynitrite and of strong oxidants and nitrating species following the reaction of peroxynitrite with CO2 (PMID:17229156)
• The structural consequences of metal ion binding to the form of hemopexin that dominates in plasma have been evaluated. (PMID:17636883)
• these observations result from the binding of heme in form beta with an orientation that differs from the crystallographically observed binding orientation for rabbit hemopexin (PMID:18044975)
• Results indicate that for the discrimination of AD from ND control subjects, measurement of a set of markers including Abeta1-42, ApoA1 and HPX improved diagnostic performance over that obtained by measurement of Abeta1-42 alone. (PMID:19863188)
• In a family with a hypomaturation-type enamel defect, mutational and haplotype analyses revealed an amelogenesis imperfecta-causing point mutation in exon 6 of MMP20 that results in a single amino acid substitution in the hemopexin domain. (PMID:19966041)
• elevated Hx predicts late graft failure in kidney transplantation (PMID:20149159)
• hemopexin directly interacts with FLVCR (PMID:20610401)
• mutations of amino acids involved in the interaction weakened the dimer interaction of Hpx domains in solution, and incorporation of these mutations into the full-length enzyme significantly inhibited dimer-dependent functions on the cell surface (PMID:21193411)
• Studies indicate that hemopexin lacks the catalytic triad that is characteristic of many serine proteases but possesses two highly exposed Arg-Gly-Glu sequences that may promote interaction with cell surfaces. (PMID:21404362)
• In conclusion, the current work has identified potential T1DM biomarkers and one of these, hemopexin, can be modulated by glucose through a ROS-dependent mechanism. (PMID:22579751)
• The findings suggest that hemopexin can modulate the role of hemoglobin in sterile and infectious inflammation (PMID:22772444)
• In sum, these data indicated that AKI-associated hepatic stress generates Hpx, which gains renal tubule access. (PMID:22993068)
• activated hemopexin might be considered as a factor mediating ang II effects upon blood pressure by modulating AT1-R availability (PMID:23254305)
• hemopexin will be neuroprotective after traumatic brain injury, with heme release in the CNS, and during the ensuing inflammation. (PMID:23350672)
• Hemopexin is overexpressed in the RPE of diabetic patients with DME and induces the breakdown of RPE cells in vitro. (PMID:23620477)
• The Bach1-dependent repression of the HO-1 expression is under the control of the Hemopexin-dependent uptake of extracellular he (PMID:24613679)
• Data show that HPX, POTEE and ApoA1 are deregulated in breast tumors suggesting un important role in breast tumorigenesis. (PMID:24969553)
• Plasma hemopexin levels were decreased or markedly decreased in patients with burns or sepsis and in premature infants. (PMID:25888135)
• Heme scavenging is a major mechanism by which Hx defends against oxidative stress and related inflammatory disorders. [Review] (PMID:26339767)
• HPX is upregulated in non-small cell lung cancer patients compared to those with benign lung disease or no lung disease. (PMID:26908325)
• There were significantly higher serum concentrations of fetal hemoglobin and alpha1-microglobulin and significantly lower first trimester serum concentrations of hemopexin in patients who later developed preeclampsia. (PMID:27155336)
• Data suggest that apo-hemopexin isolated from plasma exchibits low endogenous levels of tyrosine nitration in the peptide YYCFQGNQFLR in the heme-binding site of human hemopexin, which was similarly nitrated in rabbit and rat hemopexins; heme binding by hemopexin declined as tyrosine nitration proceeded in vitro. (PMID:28596380)
• Study found that hemopexin was significantly higher in acute T cell-mediated rejection (TCMR) patients and could be detected in urine of kidney transplant recipients which makes it s potential diagnostic protein for TCMR. (PMID:30226858)
• Hemopexin and alpha1-microglobulin heme scavengers with differential involvement in preeclampsia and fetal growth restriction. (PMID:32915914)
• Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases. (PMID:32966797)
• Widespread severe cerebral elevations of haptoglobin and haemopexin in sporadic Alzheimer’s disease: Evidence for a pervasive microvasculopathy. (PMID:33813281)
• Evaluation of the relationship between intravascular hemolysis and clinical manifestations in sickle cell disease: decreased hemopexin during vaso-occlusive crises and increased inflammation in acute chest syndrome. (PMID:34564750)
• Heme oxygenase-1 and hemopexin gene polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity in China. (PMID:35470713)
• Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia. (PMID:37899696)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	hpxb	ENSDARG00000051912
mus_musculus	Hpx	ENSMUSG00000030895
rattus_norvegicus	Hpx	ENSRNOG00000018257
caenorhabditis_elegans		WBGENE00010524
caenorhabditis_elegans		WBGENE00012185
caenorhabditis_elegans		WBGENE00012364
caenorhabditis_elegans		WBGENE00016283
caenorhabditis_elegans		WBGENE00194737

Paralogs (23): MMP25 (ENSG00000008516), MMP2 (ENSG00000087245), MMP11 (ENSG00000099953), MMP9 (ENSG00000100985), MMP15 (ENSG00000102996), MMP8 (ENSG00000118113), MMP19 (ENSG00000123342), MMP24 (ENSG00000125966), MMP7 (ENSG00000137673), MMP20 (ENSG00000137674), MMP27 (ENSG00000137675), MMP13 (ENSG00000137745), MMP3 (ENSG00000149968), MMP21 (ENSG00000154485), MMP16 (ENSG00000156103), MMP14 (ENSG00000157227), MMP10 (ENSG00000166670), MMP26 (ENSG00000167346), MMP23B (ENSG00000189409), MMP1 (ENSG00000196611), MMP17 (ENSG00000198598), MMP12 (ENSG00000262406), MMP28 (ENSG00000271447)

Protein

Protein identifiers

Hemopexin — P02790 (reviewed: P02790)

Alternative names: Beta-1B-glycoprotein

All UniProt accessions (1): P02790

UniProt curated annotations — full annotation on UniProt →

Function. Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation.

Subunit / interactions. Interacts with FLVCR1. (Microbial infection) Interacts with hepatitis E virus/HEV protein ORF3.

Subcellular location. Secreted.

Tissue specificity. Expressed by the liver and secreted in plasma.

Post-translational modifications. N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. O-glycosylation in the 30-40 region is minor compared to glycosylation at Thr-24 and Thr-29.

Miscellaneous. The isolated N-terminal domain binds one heme. The full-length protein also binds one heme, but at a different site. The physiological significance of this is not clear.

Similarity. Belongs to the hemopexin family.

RefSeq proteins (1): NP_000604* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000585	Hemopexin-like_dom	Domain
IPR016358	Hemopexin	Family
IPR018486	Hemopexin_CS	Conserved_site
IPR018487	Hemopexin-like_repeat	Repeat
IPR036375	Hemopexin-like_dom_sf	Homologous_superfamily
IPR051298	Heme_transport/Cell_adhesion	Family

Pfam: PF00045

UniProt features (33 total): repeat 8, glycosylation site 7, disulfide bond 6, binding site 4, region of interest 2, sequence variant 2, signal peptide 1, chain 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02790-F1	88.28	0.76

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 (4): 79 (axial binding residue); 150 (axial binding residue); 236 (axial binding residue); 293 (axial binding residue)

Disulfide bonds (6): 50–231, 149–154, 188–200, 257–460, 366–408, 418–435

Glycosylation sites (7): 24, 29, 64, 187, 240, 246, 453

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2168880	Scavenging of heme from plasma

MSigDB gene sets: 168 (showing top): GOBP_HEMOGLOBIN_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_IRON_COORDINATION_ENTITY_TRANSPORT, GNF2_GSTM1, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GNF2_HPN, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_B_CELL_MEDIATED_IMMUNITY, GOBP_IRON_ION_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_PORPHYRIN_CONTAINING_COMPOUND_METABOLIC_PROCESS

GO Biological Process (10): positive regulation of immunoglobulin production (GO:0002639), positive regulation of humoral immune response mediated by circulating immunoglobulin (GO:0002925), intracellular iron ion homeostasis (GO:0006879), heme transport (GO:0015886), hemoglobin metabolic process (GO:0020027), heme metabolic process (GO:0042168), regulation of protein metabolic process (GO:0051246), type II interferon-mediated signaling pathway (GO:0060333), positive regulation of type II interferon-mediated signaling pathway (GO:0060335), positive regulation of response to type II interferon (GO:0060332)

GO Molecular Function (3): heme transmembrane transporter activity (GO:0015232), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), endocytic vesicle lumen (GO:0071682), blood microparticle (GO:0072562)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Binding and Uptake of Ligands by Scavenger Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
cellular anatomical structure	2
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
humoral immune response mediated by circulating immunoglobulin	1
positive regulation of immunoglobulin mediated immune response	1
positive regulation of humoral immune response	1
regulation of humoral immune response mediated by circulating immunoglobulin	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
nitrogen compound transport	1
iron coordination entity transport	1
porphyrin-containing compound metabolic process	1
pigment metabolic process	1
regulation of macromolecule metabolic process	1
regulation of primary metabolic process	1
cellular response to type II interferon	1
interferon-mediated signaling pathway	1
positive regulation of cytokine-mediated signaling pathway	1
positive regulation of response to type II interferon	1
type II interferon-mediated signaling pathway	1
regulation of type II interferon-mediated signaling pathway	1
response to type II interferon	1
positive regulation of innate immune response	1
regulation of response to type II interferon	1
positive regulation of response to cytokine stimulus	1
heme transport	1
transmembrane transporter activity	1
cation binding	1
binding	1
external encapsulating structure	1
extracellular vesicle	1
endocytic vesicle	1
intracellular organelle lumen	1
extracellular region	1

Protein interactions and networks

STRING

1508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HPX	HP	P00737	992
HPX	LRP1	Q07954	989
HPX	ALB	P02768	942
HPX	TIMP2	P16035	932
HPX	CD163	Q86VB7	927
HPX	MMP2	P08253	874
HPX	PRG4	Q92954	855
HPX	MMP28	Q9H239	855
HPX	MMP26	Q9NRE1	836
HPX	C3	P01024	832
HPX	FLVCR1	Q9Y5Y0	827
HPX	CP	P00450	818
HPX	A2M	P01023	806
HPX	TIMP4	Q99727	797
HPX	SERPINA1	P01009	794

IntAct

59 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HPX	GALNT12	psi-mi:“MI:0915”(physical association)	0.640
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
HPX	GLUD1	psi-mi:“MI:0915”(physical association)	0.370
HPX	TP63	psi-mi:“MI:0915”(physical association)	0.370
LTN1	KIF2A	psi-mi:“MI:0914”(association)	0.350
ALB	SH3BP5	psi-mi:“MI:0914”(association)	0.350
URM1	OGT	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
SNX27	IGLL5	psi-mi:“MI:0914”(association)	0.350
GDPD1	CP	psi-mi:“MI:0914”(association)	0.350
C1QBP	IRS4	psi-mi:“MI:0914”(association)	0.350
CDC42		psi-mi:“MI:0914”(association)	0.350
CAMK2A	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
PEBP1	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
MAP2K2	DNAJA2	psi-mi:“MI:0914”(association)	0.350
PEBP1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
FGFR1	MRPS14	psi-mi:“MI:0914”(association)	0.350
BRAF	NDUFA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): ADAMTS1 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), HPX (Affinity Capture-MS), HPX (Affinity Capture-MS), HPX (Affinity Capture-MS), HPX (Affinity Capture-MS), HPX (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), HPX (Affinity Capture-MS), HPX (Affinity Capture-MS), HPX (Affinity Capture-MS), HPX (Protein-RNA), HPX (Affinity Capture-MS), HPX (Affinity Capture-MS), HPX (Affinity Capture-MS)

ESM2 similar proteins: B2RXS4, O15031, O60486, O70624, O75326, P02790, P04004, P20058, P20059, P20062, P22458, P24347, P29788, P48819, P50828, Q02853, Q0VCP3, Q2PT31, Q3SZV7, Q3U435, Q499S5, Q4LFA9, Q594P2, Q5EA85, Q5M7W6, Q5R543, Q5REL7, Q66H86, Q6UWY5, Q863A3, Q866N2, Q8C0Z1, Q8WY21, Q91X72, Q96PQ0, Q99542, Q99972, Q9EPR5, Q9H3S1, Q9JHI0

Diamond homologs: D0EM77, G5EBU3, O04529, O13065, O18767, O18927, O23507, O35548, O44836, O54732, O55123, O55761, O60882, O62806, O70138, O75900, O77656, O88272, O88676, O88766, P02790, P03956, P03957, P04004, P07152, P08253, P08254, P09237, P09238, P13943, P21692, P22458, P22757, P22894, P23097, P24347, P28053, P28862, P28863, P29136

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HPX	“down-regulates activity”	HBB

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Signaling by moderate kinase activity BRAF mutants	5	26.4×	1e-04
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	26.4×	1e-04
Signaling downstream of RAS mutants	5	26.4×	1e-04
Signaling by BRAF and RAF1 fusions	5	17.8×	7e-04
RAF/MAP kinase cascade	6	7.6×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
MAPK cascade	6	14.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	7
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

1369 predictions. Top by Δscore:

Variant	Effect	Δscore
11:6431635:CCTCA:C	donor_loss	1.0000
11:6431636:CTCA:C	donor_loss	1.0000
11:6431637:TCAC:T	donor_loss	1.0000
11:6431638:CACCT:C	donor_loss	1.0000
11:6431639:ACCT:A	donor_loss	1.0000
11:6431640:CC:C	donor_loss	1.0000
11:6431727:T:TA	donor_gain	1.0000
11:6431799:GTGCC:G	acceptor_gain	1.0000
11:6431800:TGCC:T	acceptor_gain	1.0000
11:6431801:GCC:G	acceptor_gain	1.0000
11:6431802:CC:C	acceptor_gain	1.0000
11:6431802:CCC:C	acceptor_gain	1.0000
11:6431803:CC:C	acceptor_gain	1.0000
11:6431804:C:CC	acceptor_gain	1.0000
11:6431804:C:T	acceptor_gain	1.0000
11:6431805:T:G	acceptor_loss	1.0000
11:6431640:CCTG:C	donor_gain	0.9900
11:6431812:C:CT	acceptor_gain	0.9900
11:6431813:A:T	acceptor_gain	0.9900
11:6437045:CCA:C	donor_gain	0.9900
11:6438506:CCCC:C	acceptor_gain	0.9900
11:6438507:CCC:C	acceptor_gain	0.9900
11:6438507:CCCC:C	acceptor_gain	0.9900
11:6438507:CCCCT:C	acceptor_loss	0.9900
11:6438508:CC:C	acceptor_gain	0.9900
11:6438508:CCC:C	acceptor_gain	0.9900
11:6438508:CCCTG:C	acceptor_loss	0.9900
11:6438509:CC:C	acceptor_gain	0.9900
11:6438509:CCT:C	acceptor_loss	0.9900
11:6438511:T:A	acceptor_loss	0.9900

AlphaMissense

3015 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:6431952:A:G	W301R	0.989
11:6431952:A:T	W301R	0.989
11:6437050:G:C	F277L	0.989
11:6437050:G:T	F277L	0.989
11:6437052:A:G	F277L	0.989
11:6437525:G:C	F206L	0.989
11:6437525:G:T	F206L	0.989
11:6437527:A:G	F206L	0.989
11:6431950:C:A	W301C	0.988
11:6431950:C:G	W301C	0.988
11:6437051:A:C	F277C	0.988
11:6437051:A:G	F277S	0.988
11:6437516:G:C	F209L	0.987
11:6437516:G:T	F209L	0.987
11:6437518:A:G	F209L	0.987
11:6437517:A:C	F209C	0.983
11:6437543:G:C	C200W	0.982
11:6438413:C:G	A145P	0.981
11:6431686:C:G	A362P	0.980
11:6437517:A:G	F209S	0.980
11:6431917:A:C	F312L	0.977
11:6431917:A:T	F312L	0.977
11:6431919:A:G	F312L	0.977
11:6438400:C:G	C149S	0.975
11:6438401:A:T	C149S	0.975
11:6437460:A:C	F228C	0.974
11:6437526:A:G	F206S	0.974
11:6437526:A:C	F206C	0.973
11:6437579:G:C	C188W	0.973
11:6431783:G:C	F329L	0.972

dbSNP variants (sampled 300 via entrez): RS1000336543 (11:6435231 C>A,T), RS1000383822 (11:6435105 A>G,T), RS1000397560 (11:6441118 G>T), RS1000887153 (11:6430646 T>C), RS1000955089 (11:6436742 G>A), RS1001518227 (11:6435436 T>G), RS1002503858 (11:6441726 G>C), RS1002524647 (11:6436783 T>C), RS1002554774 (11:6441912 G>A), RS1003043334 (11:6442984 A>C), RS1003081502 (11:6442686 T>C), RS1003215041 (11:6430727 T>A,C), RS1003485615 (11:6436434 T>C), RS1003528295 (11:6438167 C>T), RS1003777449 (11:6436698 G>A)

Disease associations

OMIM: gene MIM:142290 | 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
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2682099	HPX		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression, affects cotreatment	2
Aflatoxin B1	affects expression, increases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	decreases expression, affects cotreatment	1
bisphenol A	decreases expression	1
chlortoluron	decreases expression	1
decabromobiphenyl ether	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
zinc chromate	increases abundance, increases expression	1
tris(chloroethyl)phosphate	decreases expression	1
pentanal	decreases expression	1
nefazodone	affects cotreatment, decreases expression	1
tri-(2-chloroisopropyl)phosphate	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
entinostat	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
belinostat	decreases expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
(+)-JQ1 compound	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_UW80	CHO-HPX	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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