HEBP1

Summary

HEBP1 (heme binding protein 1, HGNC:17176) is a protein-coding gene on chromosome 12p13.1, encoding Heme-binding protein 1 (Q9NRV9). May bind free porphyrinogens that may be present in the cell and thus facilitate removal of these potentially toxic compound.

The full-length protein encoded by this gene is an intracellular tetrapyrrole-binding protein. This protein includes a natural chemoattractant peptide of 21 amino acids at the N-terminus, which is a natural ligand for formyl peptide receptor-like receptor 2 (FPRL2) and promotes calcium mobilization and chemotaxis in monocytes and dendritic cells.

Source: NCBI Gene 50865 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_015987

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17176
Approved symbol	HEBP1
Name	heme binding protein 1
Location	12p13.1
Locus type	gene with protein product
Status	Approved
Aliases	HEBP, HBP
Ensembl gene	ENSG00000013583
Ensembl biotype	protein_coding
OMIM	605826
Entrez	50865

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000014930, ENST00000535636, ENST00000536942, ENST00000540916, ENST00000647702, ENST00000905178, ENST00000905180

RefSeq mRNA: 1 — MANE Select: NM_015987 NM_015987

CCDS: CCDS31749

Canonical transcript exons

ENST00000014930 — 4 exons

Exon	Start	End
ENSE00000482056	12987152	12987332
ENSE00000721904	12989277	12989415
ENSE00001121981	12974870	12975479
ENSE00002307949	13000037	13000265

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7183 / max 192.1551, expressed in 1780 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129776	24.8878	1780
129777	0.5669	350
129775	0.2636	107

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.42	gold quality
duodenum	UBERON:0002114	98.90	gold quality
ileal mucosa	UBERON:0000331	98.13	gold quality
right adrenal gland	UBERON:0001233	97.52	gold quality
right adrenal gland cortex	UBERON:0035827	97.43	gold quality
left adrenal gland	UBERON:0001234	97.41	gold quality
trabecular bone tissue	UBERON:0002483	97.30	gold quality
adrenal cortex	UBERON:0001235	97.28	gold quality
parotid gland	UBERON:0001831	97.26	gold quality
left adrenal gland cortex	UBERON:0035825	97.25	gold quality
left lobe of thyroid gland	UBERON:0001120	97.01	gold quality
renal glomerulus	UBERON:0000074	96.90	gold quality
tibia	UBERON:0000979	96.90	gold quality
metanephric glomerulus	UBERON:0004736	96.87	gold quality
germinal epithelium of ovary	UBERON:0001304	96.80	gold quality
thyroid gland	UBERON:0002046	96.77	gold quality
right lobe of thyroid gland	UBERON:0001119	96.73	gold quality
vena cava	UBERON:0004087	96.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.22	gold quality
left ovary	UBERON:0002119	96.19	gold quality
small intestine	UBERON:0002108	96.14	gold quality
right lobe of liver	UBERON:0001114	96.09	gold quality
ascending aorta	UBERON:0001496	96.07	gold quality
thoracic aorta	UBERON:0001515	96.06	gold quality
adrenal gland	UBERON:0002369	96.06	gold quality
cartilage tissue	UBERON:0002418	95.97	gold quality
descending thoracic aorta	UBERON:0002345	95.95	gold quality
parietal pleura	UBERON:0002400	95.94	gold quality
mammary duct	UBERON:0001765	95.87	gold quality
adipose tissue	UBERON:0001013	95.85	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	147.26
E-GEOD-125970	yes	70.96
E-CURD-112	yes	40.84
E-CURD-122	yes	20.90
E-HCAD-1	yes	18.68
E-MTAB-6678	no	3.17
E-HCAD-10	no	2.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA1

miRNA regulators (miRDB)

22 targeting HEBP1, 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-590-3P	99.96	74.34	6478
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-6796-3P	98.68	65.49	689
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-3663-5P	97.01	64.84	713
HSA-MIR-217-3P	95.67	68.42	1000
HSA-MIR-5009-5P	94.82	63.89	775
HSA-MIR-6798-3P	94.55	68.78	325

Literature-anchored findings (GeneRIF, showing 6)

• Characterization as a tetrapyrrole-binding protein (PMID:12413491)
• F2L is a chemoattractant peptide promoting calcium mobilization and chemotaxis in dendritic cells and monocytes. [F2L] (PMID:15623572)
• mouse neutrophils, which like macrophages and dendritic cells express Fpr2, responded to human and mouse F2L in both calcium flux and chemotaxis assays (PMID:17237393)
• Results present a systematic molecular modeling study of the binding properties of murine and human p22HBP protein (heme-binding protein) with four tetrapyrrole ring systems belonging to the heme biosynthetic pathway. (PMID:20800521)
• The functional activity of purified full-length HEBP1 has been evaluated on human formyl peptide receptor (FPR)3-expressing CHO-K1 cells (PMID:21709160)
• Taken together, these data highlight a role of Hebp1 in progressive neuronal loss during Alzheimer’s disease progression. (PMID:31453805)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hebp1	ENSMUSG00000042770
rattus_norvegicus	Hebp1	ENSRNOG00000000024

Paralogs (1): HEBP2 (ENSG00000051620)

Protein

Protein identifiers

Heme-binding protein 1 — Q9NRV9 (reviewed: Q9NRV9)

Alternative names: p22HBP

All UniProt accessions (4): Q9NRV9, A0A3B3IRV5, F5GWX2, H0YG71

UniProt curated annotations — full annotation on UniProt →

Function. May bind free porphyrinogens that may be present in the cell and thus facilitate removal of these potentially toxic compound. Binds with a high affinity to one molecule of heme or porphyrins. It binds metalloporphyrins, free porphyrins and N-methylprotoporphyrin with similar affinities.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Domain organisation. Forms a distorted beta-barrel structure, with two helices that are packed against the outer surface of the barrel. Porphyrins are expected to bind to a hydrophobic patch on the outer surface of the beta-barrel structure.

Similarity. Belongs to the HEBP family.

RefSeq proteins (1): NP_057071* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006917	SOUL_heme-bd	Family
IPR011256	Reg_factor_effector_dom_sf	Homologous_superfamily

Pfam: PF04832

UniProt features (3 total): chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRV9-F1	84.90	0.52

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-444473	Formyl peptide receptors bind formyl peptides and many other ligands

MSigDB gene sets: 195 (showing top): GOBP_CIRCADIAN_RHYTHM, RRAGTTGT_UNKNOWN, GNF2_PRDX2, LFA1_Q6, GCANCTGNY_MYOD_Q6, CMYB_01, IVANOVA_HEMATOPOIESIS_MATURE_CELL, AP2_Q3, GNF2_ANK1, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, TGCTGAY_UNKNOWN, TCF11_01, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, BROWN_MYELOID_CELL_DEVELOPMENT_UP

GO Biological Process (1): circadian rhythm (GO:0007623)

GO Molecular Function (1): heme binding (GO:0020037)

GO Cellular Component (4): extracellular region (GO:0005576), mitochondrion (GO:0005739), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
Peptide ligand-binding receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
rhythmic process	1
tetrapyrrole binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HEBP1	FPR3	P25089	946
HEBP1	KRCC1	Q9NPI7	448
HEBP1	FPR2	P25090	436
HEBP1	FECH	P22830	417
HEBP1	FLVCR1	Q9Y5Y0	379
HEBP1	SLC25A37	Q9NYZ2	374
HEBP1	ADISSP	Q9GZN8	370
HEBP1	PTDSS2	Q9BVG9	351
HEBP1	PPOX	P50336	350
HEBP1	GIN1	Q9NXP7	349
HEBP1	FAM193A	P78311	348
HEBP1	PRRT3	Q5FWE3	334
HEBP1	TMEM14C	Q9P0S9	330
HEBP1	NAA38	Q9BRA0	323
HEBP1	ALAD	P13716	321
HEBP1	CPOX	P36551	321

IntAct

16 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
COQ8A	COQ9	psi-mi:“MI:0914”(association)	0.670
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
NDUFS3	ACOT7	psi-mi:“MI:0914”(association)	0.350
FMC1	DNM1L	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NMES1	COX7A2L	psi-mi:“MI:0914”(association)	0.350
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350
NMES1	TIMM44	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
USP46	UBA6	psi-mi:“MI:0914”(association)	0.350
	PSMD12	psi-mi:“MI:0914”(association)	0.350
HEBP1	metE	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): COTL1 (Co-fractionation), PCBP1 (Co-fractionation), S100A6 (Co-fractionation), SNX3 (Co-fractionation), UBE2L3 (Co-fractionation), HEBP1 (Affinity Capture-MS), HEBP1 (Affinity Capture-MS), HEBP1 (Co-fractionation), HEBP1 (Co-fractionation), HEBP1 (Co-fractionation), HEBP1 (Co-fractionation), HEBP1 (Co-fractionation), HEBP1 (Co-fractionation), HEBP1 (Co-fractionation), HEBP1 (Co-fractionation)

ESM2 similar proteins: A0A0D1CD96, A2XNR6, A2YQ56, A6R2K7, O16216, O35501, P12076, P20583, P20973, P22774, P26882, P29845, P31251, P38646, P38647, P48721, P49588, P51660, P86233, P93648, Q01899, Q02028, Q08276, Q08752, Q148C9, Q29LW1, Q3ZCH0, Q43207, Q5ISC6, Q5R511, Q5RC02, Q5ZM98, Q5ZMB2, Q69UZ3, Q6DGG0, Q6DJ66, Q6NU05, Q75LJ3, Q8BGQ7, Q8GUM2

Diamond homologs: Q148C9, Q5ISC6, Q5ZMB2, Q6DJ66, Q6NU05, Q9NRV9, Q9R257, Q9SR77, Q9Y5Z4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

668 predictions. Top by Δscore:

Variant	Effect	Δscore
12:12987150:A:AC	donor_gain	1.0000
12:12987151:C:CC	donor_gain	1.0000
12:12987179:T:A	donor_gain	1.0000
12:12989271:ACTC:A	donor_loss	1.0000
12:12989272:CTCA:C	donor_loss	1.0000
12:12989274:CA:C	donor_loss	1.0000
12:12989275:A:AC	donor_gain	1.0000
12:12989275:AC:A	donor_gain	1.0000
12:12989275:ACC:A	donor_gain	1.0000
12:12989276:C:CC	donor_gain	1.0000
12:12989276:CC:C	donor_gain	1.0000
12:12989276:CCC:C	donor_gain	1.0000
12:12989304:TTGCG:T	donor_gain	1.0000
12:12989305:TGCG:T	donor_gain	1.0000
12:12989325:C:A	donor_gain	1.0000
12:12989412:CTTC:C	acceptor_gain	1.0000
12:12989413:TTC:T	acceptor_gain	1.0000
12:12989414:TC:T	acceptor_gain	1.0000
12:12989415:CC:C	acceptor_gain	1.0000
12:12989416:C:CC	acceptor_gain	1.0000
12:12989416:C:CG	acceptor_loss	1.0000
12:12989417:T:C	acceptor_loss	1.0000
12:12975476:CTGC:C	acceptor_gain	0.9900
12:12975478:GCCTG:G	acceptor_loss	0.9900
12:12975480:C:CC	acceptor_gain	0.9900
12:12985984:A:AC	donor_gain	0.9900
12:12985985:C:CC	donor_gain	0.9900
12:12985985:CT:C	donor_gain	0.9900
12:12987080:G:A	donor_gain	0.9900
12:12987174:C:A	donor_gain	0.9900

AlphaMissense

1238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:12989371:A:C	F41L	0.994
12:12989371:A:T	F41L	0.994
12:12989373:A:G	F41L	0.994
12:12975473:A:C	F135L	0.991
12:12975473:A:T	F135L	0.991
12:12975475:A:G	F135L	0.991
12:12989369:G:T	A42D	0.989
12:12989284:A:C	N70K	0.986
12:12989284:A:T	N70K	0.986
12:12989392:C:A	R34S	0.986
12:12989392:C:G	R34S	0.986
12:12987308:G:T	P81H	0.985
12:12975426:A:G	L151P	0.984
12:12989301:A:C	Y65D	0.984
12:12989309:A:T	V62D	0.984
12:12987161:A:T	V130D	0.983
12:12989300:T:G	Y65S	0.983
12:12989301:A:G	Y65H	0.983
12:12975436:C:G	A148P	0.979
12:12987308:G:C	P81R	0.979
12:12989322:C:G	A58P	0.979
12:12975330:T:A	E183V	0.978
12:12987251:A:T	V100D	0.977
12:12975339:C:G	R180P	0.976
12:12975462:G:T	A139D	0.976
12:12975321:A:G	L186P	0.975
12:12987159:A:C	Y131D	0.975
12:12975325:A:G	W185R	0.974
12:12975325:A:T	W185R	0.974
12:12975332:A:C	N182K	0.974

dbSNP variants (sampled 300 via entrez): RS1000005752 (12:12985834 C>T), RS1000247209 (12:12988048 C>T), RS1000298413 (12:13002120 T>A), RS1000305683 (12:12993134 C>G), RS1000499875 (12:12980379 A>G), RS1000570892 (12:12978740 T>C), RS1000630815 (12:13000743 A>G), RS1000663346 (12:13001099 G>A), RS1000885232 (12:12995102 T>C), RS1000959825 (12:12980653 G>A), RS1001169003 (12:12977457 C>G), RS1001620359 (12:12977828 T>A), RS1001769925 (12:12979196 T>C,G), RS1002061219 (12:13000537 C>A), RS1002146519 (12:12998917 A>G)

Disease associations

OMIM: gene MIM:605826 | disease phenotypes: MIM:613970, MIM:616139

GenCC curated gene-disease

Mondo (2): intellectual disability, autosomal dominant 6 (MONDO:0013509), developmental and epileptic encephalopathy, 27 (MONDO:0014505)

Orphanet (2): West syndrome (Orphanet:3451), GRIN2B-related developmental delay, intellectual disability and autism spectrum disorder (Orphanet:589547)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008163_416	Height	2.000000e-06
GCST90002403_220	Red blood cell count	9.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases expression	2
Benzo(a)pyrene	increases expression	2
Estradiol	decreases expression, affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
dinophysistoxin 1	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
gardiquimod	decreases expression, decreases reaction	1
bisphenol AF	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Atrazine	increases expression	1

Clinical trials (associated diseases)

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