HBG1

Summary

HBG1 (hemoglobin subunit gamma 1, HGNC:4831) is a protein-coding gene on chromosome 11p15.4, encoding Hemoglobin subunit gamma-1 (P69891). Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.

The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5’-epsilon – gamma-G – gamma-A – delta – beta–3'.

Source: NCBI Gene 3047 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 54 total — 7 pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• MANE Select transcript: NM_000559

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4831
Approved symbol	HBG1
Name	hemoglobin subunit gamma 1
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	HBG-T2
Ensembl gene	ENSG00000213934
Ensembl biotype	protein_coding
OMIM	142200
Entrez	3047

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000330597, ENST00000632727, ENST00000648735

RefSeq mRNA: 1 — MANE Select: NM_000559 NM_000559

CCDS: CCDS7754

Canonical transcript exons

ENST00000330597 — 3 exons

Exon	Start	End
ENSE00001598355	5249368	5249590
ENSE00001873394	5248269	5248487
ENSE00001956149	5249713	5249857

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 82.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.2110 / max 191.2229, expressed in 110 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118369	2.2110	110

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	82.49	gold quality
blood	UBERON:0000178	82.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.70	gold quality
adrenal tissue	UBERON:0018303	80.61	gold quality
ganglionic eminence	UBERON:0004023	76.03	gold quality
monocyte	CL:0000576	71.81	gold quality
leukocyte	CL:0000738	70.10	gold quality
bone marrow cell	CL:0002092	69.10	gold quality
ventricular zone	UBERON:0003053	64.94	gold quality
cortical plate	UBERON:0005343	62.38	gold quality
bone marrow	UBERON:0002371	61.79	gold quality
mucosa of stomach	UBERON:0001199	61.22	gold quality
lower esophagus mucosa	UBERON:0035834	60.72	gold quality
gastrocnemius	UBERON:0001388	57.32	gold quality
heart left ventricle	UBERON:0002084	56.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.66	gold quality
lung	UBERON:0002048	55.34	gold quality
muscle of leg	UBERON:0001383	54.45	gold quality
heart	UBERON:0000948	53.91	gold quality
right lobe of liver	UBERON:0001114	53.21	gold quality
stomach	UBERON:0000945	53.01	gold quality
right atrium auricular region	UBERON:0006631	52.81	gold quality
upper lobe of left lung	UBERON:0008952	52.46	gold quality
subcutaneous adipose tissue	UBERON:0002190	52.19	gold quality
body of stomach	UBERON:0001161	52.11	gold quality
left adrenal gland	UBERON:0001234	51.80	gold quality
left coronary artery	UBERON:0001626	51.77	gold quality
adipose tissue	UBERON:0001013	51.45	gold quality
popliteal artery	UBERON:0002250	51.45	gold quality
tibial artery	UBERON:0007610	51.24	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	97201.13
E-CURD-98	yes	81067.53
E-HCAD-24	yes	41400.24
E-MTAB-9067	yes	36517.05
E-MTAB-7407	yes	29278.20
E-CURD-112	yes	10092.21
E-MTAB-8205	yes	7431.85
E-ANND-5	yes	1042.57
E-HCAD-32	yes	174.97
E-MTAB-8207	yes	122.72
E-MTAB-9388	yes	9.62
E-HCAD-10	yes	8.38
E-MTAB-7303	no	4.98
E-ANND-3	no	1.26

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• Developmental specificity of recruitment of TBP to the TATA box of the human gamma-globin gene (PMID:11960008)
• DRED binds with high affinity to DR1 sites in the human epsilon & gamma globin promoters, but the adult beta-globin promoter has no DR1 element. An HPFH mutation in a DR1 site causes elevated gamma-globin transcription & reduces TR2/TR4 binding in vitro. (PMID:12093744)
• Apicidin activates the A gamma globin gene promoter. Activation of the Agamma-globin promoter by apicidin could be inhibited by p38 inhibitor SB203580 (PMID:12393499)
• In transgenic mice treated with short-chain fatty acid derivatives once daily for 5 days, human gamma globin mRNA increased 2-fold, reticulocytes increased 2-fold. (PMID:12393583)
• human gamma-globin gene expression is developmentally regulated by the CCAAT box (PMID:14645237)
• in an Albanian family, two mutations of the gamma-globin promoter (for both HBG1 and HBG2) are assoicated in trans with a beta thal point mutation, that results in increased levels of HbF (PMID:14649320)
• a multiprotein complex containing GATA-1, Oct-1, and other protein factors may contribute to the formation of a repressive chromatin structure that silences gamma-globin gene expression (PMID:15613485)
• Direct repeat element in the promoter region of the gamma-globin gene autonomously mediates definitive stage-specific gene silencing. (PMID:15831451)
• Together, these results show that the cAMP pathway blocks gamma-globin gene expression in K562 cells by increasing c-Myb expression. (PMID:16631597)
• A novel gamma-globin-inducing short-chain fatty acid derivative (SCFAD), RB7, which was identified through computational modeling, produced a 6-fold induction in a reporter assay. (PMID:16849648)
• These results suggest that different PKC isoforms may exert ontogenetic-specific functions in erythropoiesis and that modulation of PKCalpha might affect the activity of (A)gamma-promoter-driven reporters. (PMID:17212360)
• data provide important clues for identifying and validating trans-activators that activate the gamma-globin gene in fetuses, and trans-acting factors involved in silencing the gamma-globin gene in adults (PMID:17612629)
• This work describes the study of the interactions of different hemoglobin variants HbA, HbE and HbF and the globin subunits of HbA with the two aminophospholipids in the presence and absence of cholesterol. (PMID:17916326)
• analysis of a model for dynamic post-transcriptional control of gamma-globin gene expression, through modulation of the stability of its encoding mRNA (PMID:17976188)
• study reports 2 new forms of nondeletional hereditary persistence of fetal hemoglobin; the presence of a (G)gamma-196 C–>T in the first case and an (A)gamma-201 C–>T in the second was revealed (PMID:18096417)
• during definitive erythropoiesis, gamma-globin gene expression is silenced, in part, by binding a protein complex containing GATA-1, FOG-1, and Mi2 at the -566/-567 GATA sites of the proximal gamma-globin promoters (PMID:18347053)
• Very low HBA2 levels of HBA2 in compound heterozygotes result from functional inhibition of the HBD gene in cis to the HBG1 gene bearing the nd-HPFH mutation. Absence of the HBG1:g.-225-222AGCAdel variation correlated with lower HbF & higher HbA2 levels. (PMID:18615450)
• Observations from these two unique cases provide solid evidence that the Alphagamma - 158 C > T mutation plays an important role in Agamma-globin gene transcription. (PMID:18718799)
• EKLF and the co-activator BRG1 are co-opted by short-chain fatty acid derivatives to activate the gamma globin genes (PMID:19220418)
• Disrupting the bindings of the Oct-1 transcriptional factors with the decoy oligonucleotide provides a novel approach for inducing expression of the gamma-globin genes. (PMID:19327156)
• The data suggest that miR-210 might be involved in increased expression of gamma-globin genes in differentiating erythroid cells. (PMID:19712585)
• Low-dose hydroxyurea combined with sodium butyrate can up-regulate gamma globin gene expression in human erythroid progenitor cells. (PMID:19861270)
• the A allele of -588, [+] allele of XmnI and HS-111 (-21 A) variation are useful genetic markers to differentiate between beta-thalassemia major and beta-thalassemia intermedia patients (PMID:19958188)
• the gamma-globin -195 mutation is the unique cause of elevation of Hb F in Brazilian hereditary persistence of fetal hemoglobin (PMID:19958189)
• role of the hematopoietic transcription factor GATA-1, its cofactor FOG-1, and the associated chromatin remodeling complex NuRD in the developmental silencing of HBG1 and HBG2 gene expression (PMID:20439494)
• Sodium butyrate increases the level of acetylated histone in gamma-globin gene promoter regions. (PMID:20584642)
• polymorphisms -396_-391 del HBG2, -369 SNP HBG2 and -271 SNP HBG1 correlated with HbF levels, hence, it suggests an important role of HBG2 and HBG1 gene polymorphisms on the HbF synthesis. (PMID:20602015)
• KLF1 controls globin gene switching by directly activating beta-globin and indirectly repressing gamma-globin gene expression. (PMID:20676097)
• Xmn I polymorphism associated with concomitant activation of Ggamma and Agamma globin gene transcription on a beta0-thalassemia chromosome. (PMID:21144779)
• Alternative NLI complexes mediate gamma-globin transcription or silencing through long-range locus control region interactions involving an intergenic site of noncoding RNA transcription and that ETO2 is critical to this process. (PMID:22010104)
• Three different gene rearrangements in three unrelated patients with the same breakpoints in the gamma-globin gene can lead to different levels of Hb A2 depending on the remaining number of gamma-globin genes. (PMID:22273484)
• Activation of the p38 MAPK pathway by sodium butyrate augments gamma-globin expression through a CREB1 response element (CRE) that is present in the upstream promoter region of Ggamma gene. (PMID:22469229)
• data are consistent with a model in which WDR5 binds the gamma-globin promoter in a PRMT5-dependent manner. (PMID:22689669)
• Methylation sites 28, 122, 231 and 234 bp of gamma-globin gene promoter are found both in patients with beta-thalassemia major and healthy adults. (PMID:22739173)
• results establish SATB2 as a novel gamma-globin gene regulator and provide a glimpse of the differential and cooperative roles of SATB family proteins in modulating clustered genes transcription (PMID:22825848)
• NF-Y recruits the developmentally regulated, erythroid transcription activator GATA-2 and general repressor BCL11A to modulate transcription of the gamma-globin gene. (PMID:23071749)
• the stimulation of GPCRs supports the postulated connection between cAMP/PKA and NO/cGMP pathways in activation of gamma-globin expression, via JUN and p38 MAPK signaling. (PMID:23425329)
• Data suggest that segregation of BCL11A haplotype 2 indicating an involvement of this locus in Hb F expression. (PMID:23777413)
• Data indicate that in embryonic stem cells (hESCs)-derived erythroblasts where both epsilon and gamma globin were active, epsilon globin was immediately silenced upon transfer, whereas gamma globin continued to be expressed for months. (PMID:23993951)
• There is synergism between developmental stage-specific recruitments of the ATF2 protein complex and expression of gamma-globin during erythropoiesis. (PMID:24223142)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	hbae5	ENSDARG00000045142
danio_rerio	hbaa2	ENSDARG00000069735
danio_rerio	si:ch211-5k11.8	ENSDARG00000079078
danio_rerio	hbae3	ENSDARG00000079305
danio_rerio	hbae1.2	ENSDARG00000088330
danio_rerio	hbae1.3	ENSDARG00000089124
danio_rerio	hbae1.1	ENSDARG00000089475
danio_rerio	hbaa1	ENSDARG00000097011
drosophila_melanogaster	glob1	FBGN0027657
caenorhabditis_elegans		WBGENE00008996
caenorhabditis_elegans		WBGENE00077763

Paralogs (11): HBQ1 (ENSG00000086506), HBZ (ENSG00000130656), CYGB (ENSG00000161544), HBA2 (ENSG00000188536), HBG2 (ENSG00000196565), MB (ENSG00000198125), HBA1 (ENSG00000206172), HBM (ENSG00000206177), HBE1 (ENSG00000213931), HBD (ENSG00000223609), HBB (ENSG00000244734)

Protein

Protein identifiers

Hemoglobin subunit gamma-1 — P69891 (reviewed: P69891)

Alternative names: Gamma-1-globin, Hb F Agamma, Hemoglobin gamma-1 chain, Hemoglobin gamma-A chain

All UniProt accessions (3): A0A0J9YYA3, D9YZU8, P69891

UniProt curated annotations — full annotation on UniProt →

Function. Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.

Subunit / interactions. Heterotetramer of two alpha chains and two gamma chains in fetal hemoglobin (Hb F). In the case of deletions affecting one or more of the alpha chains, the excess gamma chains form homotetramers that exhibit neither Bohr effect nor heme-heme cooperativity (hemoglobin Bart’s).

Tissue specificity. Red blood cells.

Post-translational modifications. Acetylation of Gly-2 converts Hb F to the minor Hb F1.

Induction. By 5-azacytidine.

Polymorphism. The variant Thr-76 shown in this entry has been called Sardinia.

Similarity. Belongs to the globin family.

RefSeq proteins (1): NP_000550* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000971	Globin	Domain
IPR002337	Hemoglobin_b	Family
IPR009050	Globin-like_sf	Homologous_superfamily
IPR012292	Globin/Proto	Homologous_superfamily
IPR050056	Hemoglobin_oxygen_transport	Family

Pfam: PF00042

UniProt features (52 total): sequence variant 25, helix 12, modified residue 9, binding site 2, initiator methionine 1, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1I3D	X-RAY DIFFRACTION	1.7
1I3E	X-RAY DIFFRACTION	1.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P69891-F1	96.89	0.98

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 (2): 64 (distal binding residue); 93 (proximal binding residue)

Post-translational modifications (9): 60, 83, 94, 140, 2, 13, 45, 51, 53

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 123 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_ERYTHROCYTE_HOMEOSTASIS, TANG_SENESCENCE_TP53_TARGETS_UP, MODULE_331, GOBP_ONE_CARBON_COMPOUND_TRANSPORT, GOBP_GAS_TRANSPORT, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, GOBP_OXYGEN_TRANSPORT, BASSO_HAIRY_CELL_LEUKEMIA_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_DN, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_UP

GO Biological Process (3): carbon dioxide transport (GO:0015670), oxygen transport (GO:0015671), erythrocyte development (GO:0048821)

GO Molecular Function (5): oxygen carrier activity (GO:0005344), oxygen binding (GO:0019825), heme binding (GO:0020037), hemoglobin alpha binding (GO:0031721), metal ion binding (GO:0046872)

GO Cellular Component (3): cytosol (GO:0005829), hemoglobin complex (GO:0005833), haptoglobin-hemoglobin complex (GO:0031838)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gas transport	2
protein-containing complex	2
one-carbon compound transport	1
erythrocyte differentiation	1
myeloid cell development	1
oxygen transport	1
oxygen binding	1
molecular carrier activity	1
small molecule binding	1
tetrapyrrole binding	1
hemoglobin binding	1
cation binding	1
cytoplasm	1
cellular anatomical structure	1
cytosol	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

11 interactions, top by confidence:

A	B	Type	Score
HBZ	HBB	psi-mi:“MI:0915”(physical association)	0.860
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
HBG1	HBG2	psi-mi:“MI:0915”(physical association)	0.400
HBZ	HBG1	psi-mi:“MI:0915”(physical association)	0.400
HBE1	HBB	psi-mi:“MI:0914”(association)	0.350
HBE1	HBG1	psi-mi:“MI:0914”(association)	0.350
VCAM1		psi-mi:“MI:0914”(association)	0.350
GABARAPL2	HBG1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): KRTAP10-9 (Two-hybrid), KRTAP10-3 (Two-hybrid), HBG1 (Two-hybrid), HBG1 (Affinity Capture-MS), HBG1 (Affinity Capture-MS), HBG1 (Affinity Capture-MS), HBG1 (Affinity Capture-MS), HBG1 (Proximity Label-MS), HBG1 (Two-hybrid), HBG1 (Affinity Capture-MS), HBG1 (Affinity Capture-MS), HBG1 (Affinity Capture-MS), HBG1 (Affinity Capture-MS), HBG1 (Affinity Capture-MS), HBG1 (Affinity Capture-MS)

ESM2 similar proteins: B3EWD0, B3EWD2, P01947, P01976, P01977, P01978, P01979, P01982, P01983, P02001, P02002, P02004, P02097, P04246, P07413, P10059, P11025, P14523, P14527, P18435, P18995, P18996, P19831, P41331, P61920, P61921, P61947, P61948, P62741, P62742, P68030, P68031, P68077, P68078, P68079, P68256, P68257, P68258, P69891, P69892

Diamond homologs: B3EWR8, C0HJT6, C0HJT7, K7N5M6, O09232, O13077, O13078, O13163, O13164, O93348, O93349, O93351, P02097, P02112, P02114, P02115, P02116, P02121, P02124, P02125, P02139, P02140, P02141, P02142, P04443, P07406, P08851, P0C0U8, P0C239, P0C240, P10058, P10782, P11025, P11342, P11749, P14521, P16309, P16418, P18995, P23017

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
BCL11A	“down-regulates quantity by repression”	HBG1	“transcriptional regulation”
CTDSPL2	“up-regulates quantity by expression”	HBG1	“transcriptional regulation”
GATA1	“down-regulates quantity by repression”	HBG1	“transcriptional regulation”
SOX6	“down-regulates quantity by repression”	HBG1	“transcriptional regulation”
EIF2S1	“up-regulates quantity by expression”	HBG1	“transcriptional regulation”
KLF11	“up-regulates quantity by expression”	HBG1	“transcriptional regulation”
HOXB6	“down-regulates quantity by repression”	HBG1	“transcriptional regulation”
NFE2	“up-regulates quantity by expression”	HBG1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	0
Uncertain significance	11
Likely benign	6
Benign	8

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
15030	NC_000011.10:g.5249974C>T	Pathogenic
15031	NC_000011.10:g.5250055A>G	Pathogenic
15033	NC_000011.10:g.5250053G>A	Pathogenic
15034	NC_000011.10:g.5250052G>C	Pathogenic
15035	NC_000011.10:g.5249971G>A	Pathogenic
15038	HBG1, 4-BP DEL, -222 TO -225, PROMOTER	Pathogenic
15040	NC_000011.10:g.5250015G>A	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

962 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:5249371:G:C	F104L	0.997
11:5249371:G:T	F104L	0.997
11:5249373:A:G	F104L	0.997
11:5249554:A:C	F43L	0.996
11:5249554:A:T	F43L	0.996
11:5249556:A:G	F43L	0.996
11:5249545:A:C	F46L	0.993
11:5249545:A:T	F46L	0.993
11:5249547:A:G	F46L	0.993
11:5249406:G:C	H93D	0.991
11:5249372:A:G	F104S	0.990
11:5249374:G:C	N103K	0.990
11:5249374:G:T	N103K	0.990
11:5249489:C:A	G65V	0.990
11:5249489:C:T	G65D	0.990
11:5249501:A:T	V61D	0.989
11:5248412:A:G	W131R	0.988
11:5248412:A:T	W131R	0.988
11:5249404:G:C	H93Q	0.987
11:5249404:G:T	H93Q	0.987
11:5249406:G:T	H93N	0.985
11:5249493:G:C	H64D	0.985
11:5249555:A:G	F43S	0.985
11:5249557:G:C	F42L	0.985
11:5249557:G:T	F42L	0.985
11:5249559:A:G	F42L	0.985
11:5249372:A:C	F104C	0.984
11:5249556:A:T	F43I	0.984
11:5249509:G:C	N58K	0.981
11:5249509:G:T	N58K	0.981

dbSNP variants (sampled 300 via entrez): RS1000084229 (11:5249906 C>T), RS1000539452 (11:5248794 A>T), RS1001081211 (11:5248078 C>A,G,T), RS1001144642 (11:5247852 T>C), RS1002187788 (11:5251277 G>A), RS1004862509 (11:5251104 A>G), RS1005083647 (11:5250796 G>T), RS1007750576 (11:5248578 C>A), RS1008418661 (11:5251831 T>A,C), RS1009431752 (11:5251475 C>T), RS1010102353 (11:5249982 G>A), RS1010534177 (11:5251364 G>A), RS1011782802 (11:5251310 ATAAAAT>A), RS1011851347 (11:5251586 G>A,T), RS1012347938 (11:5248053 C>T)

Disease associations

OMIM: gene MIM:142200 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome	Strong	Autosomal dominant
delta-beta-thalassemia	Supportive	Autosomal recessive
hereditary persistence of fetal hemoglobin-sickle cell disease syndrome	Supportive	Autosomal recessive

Mondo (4): hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome (MONDO:0018749), hereditary persistence of fetal hemoglobin (MONDO:0020989), delta-beta-thalassemia (MONDO:0016489), hereditary persistence of fetal hemoglobin-sickle cell disease syndrome (MONDO:0016672)

Orphanet (2): Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome (Orphanet:46532), Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome (Orphanet:251380)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000488	Retinopathy
HP:0000980	Pallor
HP:0001744	Splenomegaly
HP:0001746	Asplenia
HP:0001903	Anemia
HP:0001923	Reticulocytosis
HP:0001935	Microcytic anemia
HP:0002027	Abdominal pain
HP:0002113	Pulmonary infiltrates
HP:0002240	Hepatomegaly
HP:0002829	Arthralgia
HP:0003330	Abnormal bone structure
HP:0004840	Hypochromic microcytic anemia
HP:0008346	Increased red cell sickling tendency
HP:0011902	Abnormal hemoglobin
HP:0011904	Persistence of hemoglobin F
HP:0032169	Severe infection
HP:0034336	Splenic infarction
HP:0045047	HbS hemoglobin

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562716	Delta-Beta Thalassemia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066459 (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
6.48	Kd	330.1	nM	CHEMBL5653589
6.48	ED50	330.1	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	2148487: Binding affinity to human HBG1 incubated for 45 mins by Kinobead based pull down assay	kd	0.3301	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
propionaldehyde	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
2-tert-butylhydroquinone	increases expression	1
tetrabromobisphenol A	decreases expression	1
hydroquinone	affects binding, decreases reaction	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Irinotecan	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Endosulfan	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Progesterone	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Sodium Selenite	decreases 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
CHEMBL5651529	Binding	Binding affinity to human HBG1 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

Cellosaurus cell lines

1 cell lines: 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_N053	GM06342	Finite cell line	Male

Clinical trials (associated diseases)

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