HEMGN

Summary

HEMGN (hemogen, HGNC:17509) is a protein-coding gene on chromosome 9q22.33, encoding Hemogen (Q9BXL5). Regulates the proliferation and differentiation of hematopoietic cells.

Predicted to be involved in regulation of osteoblast differentiation. Located in nucleoplasm.

Source: NCBI Gene 55363 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_197978

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17509
Approved symbol	HEMGN
Name	hemogen
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	EDAG, CT155, NDR
Ensembl gene	ENSG00000136929
Ensembl biotype	protein_coding
OMIM	610715
Entrez	55363

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000259456, ENST00000616898

RefSeq mRNA: 2 — MANE Select: NM_197978 NM_018437, NM_197978

CCDS: CCDS6731

Canonical transcript exons

ENST00000616898 — 4 exons

Exon	Start	End
ENSE00003733447	97938058	97938172
ENSE00003888953	97930035	97931221
ENSE00003891691	97926791	97927478
ENSE00003894845	97936171	97936264

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 98.80.

FANTOM5 (CAGE): breadth broad, TPM avg 11.8886 / max 3615.9078, expressed in 184 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101645	11.1295	172
101647	0.3634	39
101646	0.2400	28
101644	0.0569	17
101649	0.0557	3
101643	0.0365	14
101650	0.0065	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	98.80	gold quality
sperm	CL:0000019	98.36	gold quality
bone marrow	UBERON:0002371	96.46	gold quality
bone marrow cell	CL:0002092	94.34	gold quality
monocyte	CL:0000576	92.11	gold quality
right testis	UBERON:0004534	90.86	gold quality
left testis	UBERON:0004533	90.63	gold quality
leukocyte	CL:0000738	90.09	gold quality
testis	UBERON:0000473	88.66	gold quality
blood	UBERON:0000178	81.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.75	gold quality
adrenal tissue	UBERON:0018303	79.02	gold quality
adult organism	UBERON:0007023	74.94	gold quality
kidney epithelium	UBERON:0004819	74.36	gold quality
cardiac muscle of right atrium	UBERON:0003379	72.58	gold quality
left ventricle myocardium	UBERON:0006566	72.46	gold quality
epithelial cell of pancreas	CL:0000083	69.88	gold quality
ganglionic eminence	UBERON:0004023	63.95	gold quality
placenta	UBERON:0001987	63.75	gold quality
thymus	UBERON:0002370	63.25	silver quality
upper arm skin	UBERON:0004263	62.77	gold quality
amniotic fluid	UBERON:0000173	61.60	gold quality
spleen	UBERON:0002106	61.34	gold quality
myocardium	UBERON:0002349	59.96	gold quality
right lung	UBERON:0002167	59.82	gold quality
tibialis anterior	UBERON:0001385	59.51	silver quality
vermiform appendix	UBERON:0001154	57.99	gold quality
granulocyte	CL:0000094	57.73	gold quality
lymph node	UBERON:0000029	57.57	gold quality
lower lobe of lung	UBERON:0008949	57.04	silver quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	1812.01
E-CURD-112	yes	1451.86
E-MTAB-7407	yes	947.64
E-MTAB-10042	yes	748.70
E-HCAD-6	yes	20.27
E-MTAB-9221	yes	18.88
E-HCAD-9	yes	9.18
E-HCAD-10	yes	6.17
E-GEOD-100618	no	543.65
E-MTAB-9067	no	4.70
E-MTAB-9467	no	2.63
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, GATA1

miRNA regulators (miRDB)

48 targeting HEMGN, 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-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
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-3173-3P	99.98	66.49	1217
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-567	99.63	68.57	1219

Literature-anchored findings (GeneRIF, showing 15)

• results suggest a novel function of nuclear negative differentiation regulator (NDR) protein in regulating hematopoietic cell development [NDR] (PMID:14730214)
• These results suggest that EDAG regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of NF-kappa B. (PMID:15332117)
• Hemgn promoter contains critical regulatory elements for its transcription in hematopoietic tissues and Hemgn is a direct target of GATA1 in leukemia cells (PMID:16437149)
• The stable transfected cells were identified with RT-PCR and the effect of EDAG/siRNA on the growth of the human erythroleukemia cell line HEL was analyzed. (PMID:17671716)
• The inhibition of the EDAG gene by PMA is mediated through down-regulation of transcription factor GATA-1 . (PMID:18599389)
• EDAG functions as a positive regulator of erythroid/megakaryocytic differentiation in 32D cells associated with the induction of GATA-1 and its target genes (PMID:20564185)
• EDAG enhances the protein stability of NPM1 via binding to NPM1, which plays a critical role in the anti-apoptosis of leukaemia cells. (PMID:22712502)
• EDAG forms complex with GATA1 and p300 and increases GATA1 acetylation and transcriptional activity by facilitating the interaction between GATA1 and p300 (PMID:24740910)
• EDAG-1 regulates the proliferation and apoptosis of thyroid carcinoma via the PI3K/Akt signaling pathway. (PMID:27261581)
• a 7-gene signature was identified which correctly predicted the primary prefibrotic myelofibrosis group with a sensitivity of 100% and a specificity of 89%. The 7 genes included MPO, CEACAM8, CRISP3, MS4A3, CEACAM6, HEMGN, and MMP8 (PMID:27579896)
• Using ex vivo culture and HSC transplantation models, study finds that EDAG enhances proliferative potential of human cord blood CD34+ cells, increases survival, prevents cell apoptosis and promotes their repopulating capacity. EDAG overexpression induces rapid entry of CD34+ cells into the cell cycle. Gene expression profile analysis shows that EDAG knockdown leads to down-regulation of positive cell cycle regulators. (PMID:29324880)
• EDAG mediates Hsp70 nuclear localization in erythroblasts and rescues dyserythropoiesis in myelodysplastic syndrome. (PMID:32350948)
• Circ_PSD3 promotes the progression of papillary thyroid carcinoma via the miR-637/HEMGN axis. (PMID:33203523)
• HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening. (PMID:33451334)
• Cancer/testis antigen HEMGN correlated with immune infiltration serves as a prognostic biomarker in lung adenocarcinoma. (PMID:36563642)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hemgn	ENSMUSG00000028332
mus_musculus	Hemgnl	ENSMUSG00000121974
rattus_norvegicus	Hemgn	ENSRNOG00000009436

Protein

Protein identifiers

Hemogen — Q9BXL5 (reviewed: Q9BXL5)

Alternative names: Erythroid differentiation-associated gene protein, Hemopoietic gene protein, Negative differentiation regulator protein

All UniProt accessions (1): Q9BXL5

UniProt curated annotations — full annotation on UniProt →

Function. Regulates the proliferation and differentiation of hematopoietic cells. Overexpression block the TPA-induced megakaryocytic differentiation in the K562 cell model. May also prevent cell apoptosis through the activation of the nuclear factor-kappa B (NF-kB).

Subcellular location. Nucleus.

Tissue specificity. Expressed in hematopoietic precursor cells, thyroid and spermatids (at protein level). Expressed in bone marrow, testis, thymus. Expressed in prostate cancer and ovarian cancer. Also expressed in thymus and thyroid tumors, non-Hodgkin lymphoma, various leukemia cell lines, peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of patients with leukemia.

Induction. Down-regulated during megakaryocytic differentiation of K562 cells by 12-O-tetradecanoylphorbol-13-acetate (TPA) (at protein level). Up-regulated in normal PBMCs by mitogens.

RefSeq proteins (2): NP_060907, NP_932095* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033272	Hemogen	Family

UniProt features (26 total): modified residue 11, region of interest 6, compositionally biased region 6, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXL5-F1	54.29	0.04

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 (11): 123, 159, 181, 188, 201, 246, 349, 353, 360, 363, 367

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_OSTEOBLAST_DIFFERENTIATION, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, RACCACAR_AML_Q6, GOLDRATH_ANTIGEN_RESPONSE, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, CCCNNNNNNAAGWT_UNKNOWN, GOBP_OSSIFICATION, GOBP_REGULATION_OF_OSTEOBLAST_DIFFERENTIATION, AACTTT_UNKNOWN, AFFAR_YY1_TARGETS_UP, chr9q22, WESTON_VEGFA_TARGETS, WESTON_VEGFA_TARGETS_3HR

GO Biological Process (2): cell differentiation (GO:0030154), regulation of osteoblast differentiation (GO:0045667)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): nucleoplasm (GO:0005654), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular developmental process	1
osteoblast differentiation	1
regulation of cell differentiation	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

740 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HEMGN	TRMO	Q9BU70	802
HEMGN	FOXE1	O00358	617
HEMGN	ADTRP	Q96IZ2	491
HEMGN	ZNF202	O95125	491
HEMGN	STK32B	Q9NY57	491
HEMGN	TBX10	O75333	444
HEMGN	EVC2	Q86UK5	442
HEMGN	F13A1	P00488	441
HEMGN	STX18	Q9P2W9	440
HEMGN	CRMP1	Q14194	436
HEMGN	TMPRSS12	Q86WS5	433
HEMGN	USP17L19	D6RCP7	432
HEMGN	WNT11	O96014	429
HEMGN	SATB2	Q9UPW6	427
HEMGN	SCN3B	Q9NY72	426
HEMGN	MAFB	Q9Y5Q3	426

IntAct

32 interactions, top by confidence:

A	B	Type	Score
NPM1	HEMGN	psi-mi:“MI:0915”(physical association)	0.600
HEMGN	NPM1	psi-mi:“MI:0915”(physical association)	0.600
HEMGN	NPM1	psi-mi:“MI:0403”(colocalization)	0.600
NPM1	HEMGN	psi-mi:“MI:0403”(colocalization)	0.600
HEMGN	NPM1	psi-mi:“MI:0914”(association)	0.600
CTBP1	HEMGN	psi-mi:“MI:0915”(physical association)	0.510
HEMGN	CTBP1	psi-mi:“MI:0915”(physical association)	0.510
AURKA	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
HEMGN	AXIN2	psi-mi:“MI:0915”(physical association)	0.370
HEMGN	BCL10	psi-mi:“MI:0915”(physical association)	0.370
HEMGN	BUB1	psi-mi:“MI:0915”(physical association)	0.370
CDH1	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
HEMGN	DCC	psi-mi:“MI:0915”(physical association)	0.370
DLC1	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
EGFR	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
HEMGN	FBXW7	psi-mi:“MI:0915”(physical association)	0.370
FLCN	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
KRAS	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
HEMGN	MCC	psi-mi:“MI:0915”(physical association)	0.370
MLH3	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
NRAS	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
ODC1	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
HEMGN	PTPRJ	psi-mi:“MI:0915”(physical association)	0.370
HEMGN	SMAD4	psi-mi:“MI:0915”(physical association)	0.370
HEMGN	SRC	psi-mi:“MI:0915”(physical association)	0.370
TLR2	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
CBX5	PRMT5	psi-mi:“MI:0914”(association)	0.350
HNRNPC	SBNO1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (55): EP300 (Affinity Capture-Western), GATA1 (Affinity Capture-Western), HEMGN (Affinity Capture-Western), HEMGN (Affinity Capture-Western), COPS4 (Two-hybrid), CTBP1 (Two-hybrid), ENO1 (Two-hybrid), EP300 (Two-hybrid), FBL (Two-hybrid), GATA1 (Two-hybrid), HIST1H2AC (Two-hybrid), HMG20A (Two-hybrid), HMGA1 (Two-hybrid), HSPA1A (Two-hybrid), HSPA8 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTH6, A0A1B0GUW6, A0A1D5RMD1, A2AQH4, A4FU49, A6NJ88, C4P6S0, D3YU32, E9PAV3, F1QU13, I3L273, J3KML8, P70670, Q32L62, Q3V0E1, Q3V3Q4, Q4R729, Q5H9F3, Q5QJ38, Q5SWP3, Q5U4C1, Q5VWK0, Q5VYM1, Q68DN1, Q6AZ54, Q7TSG5, Q810T2, Q8CH19, Q8K4E0, Q8N3K9, Q8N5Q1, Q8NDH2, Q8TCU4, Q8WNU4, Q8WWL7, Q920R4, Q921B4, Q923B3, Q96JA4, Q96M34

Diamond homologs: Q32L62, Q6AZ54, Q9BXL5, Q9ERZ0

SIGNOR signaling

0 interactions.

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	60
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

351 predictions. Top by Δscore:

Variant	Effect	Δscore
9:97927474:CATTT:C	acceptor_gain	0.9900
9:97927475:ATTTC:A	acceptor_loss	0.9900
9:97927476:TTT:T	acceptor_gain	0.9900
9:97927476:TTTCT:T	acceptor_loss	0.9900
9:97927478:TCT:T	acceptor_loss	0.9900
9:97927479:C:CC	acceptor_gain	0.9900
9:97927479:CT:C	acceptor_loss	0.9900
9:97927480:T:G	acceptor_loss	0.9900
9:97930032:T:TA	donor_loss	0.9900
9:97930033:A:AA	donor_loss	0.9900
9:97930034:CC:C	donor_loss	0.9900
9:97930067:T:TA	donor_gain	0.9900
9:97931218:TTCT:T	acceptor_gain	0.9900
9:97931219:TCT:T	acceptor_gain	0.9900
9:97931220:CT:C	acceptor_gain	0.9900
9:97931220:CTC:C	acceptor_gain	0.9900
9:97931220:CTCTG:C	acceptor_loss	0.9900
9:97931221:TCT:T	acceptor_gain	0.9900
9:97931221:TCTGC:T	acceptor_loss	0.9900
9:97931222:C:CC	acceptor_gain	0.9900
9:97931222:CT:C	acceptor_loss	0.9900
9:97931223:T:A	acceptor_loss	0.9900
9:97927477:TT:T	acceptor_gain	0.9800
9:97927488:CAAA:C	acceptor_gain	0.9800
9:97931217:GTTCT:G	acceptor_gain	0.9800
9:97931222:C:G	acceptor_gain	0.9800
9:97931225:C:CT	acceptor_gain	0.9700
9:97931226:A:T	acceptor_gain	0.9700
9:97936192:T:TA	donor_gain	0.9700
9:97927475:ATTT:A	acceptor_gain	0.9600

AlphaMissense

3217 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:97936233:T:A	R37S	0.935
9:97936233:T:G	R37S	0.935
9:97936239:T:A	R35S	0.925
9:97936239:T:G	R35S	0.925
9:97936215:T:A	R43S	0.923
9:97936215:T:G	R43S	0.923
9:97927387:A:C	F484L	0.912
9:97927387:A:T	F484L	0.912
9:97927389:A:G	F484L	0.912
9:97936211:C:G	A45P	0.867
9:97936221:T:A	R41S	0.857
9:97936221:T:G	R41S	0.857
9:97936225:A:G	L40P	0.857
9:97936212:T:A	K44N	0.847
9:97936212:T:G	K44N	0.847
9:97936179:C:A	W55C	0.834
9:97936179:C:G	W55C	0.834
9:97936218:T:A	K42N	0.829
9:97936218:T:G	K42N	0.829
9:97936181:A:G	W55R	0.827
9:97936181:A:T	W55R	0.827
9:97936240:C:G	R35T	0.811
9:97936234:C:G	R37T	0.764
9:97936216:C:G	R43T	0.759
9:97936234:C:A	R37I	0.752
9:97936243:A:G	L34S	0.751
9:97936219:T:A	K42I	0.742
9:97936219:T:G	K42T	0.716
9:97936235:T:C	R37G	0.711
9:97936240:C:A	R35I	0.707

dbSNP variants (sampled 300 via entrez): RS1000092327 (9:97944167 T>A,C), RS1000272795 (9:97941226 A>T), RS1000736294 (9:97936001 T>A), RS1000803091 (9:97928045 G>C,T), RS1000877576 (9:97944528 G>T), RS1001059725 (9:97937378 C>T), RS1001067694 (9:97927669 A>G), RS1001329243 (9:97927756 G>A), RS1001387752 (9:97937138 C>G), RS1001401605 (9:97932393 T>C), RS1001489301 (9:97942403 C>A), RS1001601088 (9:97932127 A>C), RS1001654103 (9:97933737 A>C), RS1001725713 (9:97940550 A>G), RS1001747446 (9:97933961 G>A)

Disease associations

OMIM: gene MIM:610715 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000337_27	Quantitative traits	1.000000e-06
GCST000640_1	Thyroid cancer (Papillary, radiation-related)	5.000000e-12
GCST004603_94	Platelet count	2.000000e-23
GCST004607_109	Plateletcrit	1.000000e-22
GCST004616_203	Platelet distribution width	2.000000e-18
GCST004866_3	Alopecia areata	9.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation	2
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	affects expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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