HBQ1

Summary

HBQ1 (hemoglobin subunit theta 1, HGNC:4833) is a protein-coding gene on chromosome 16p13.3, encoding Hemoglobin subunit theta-1 (P09105).

Theta-globin mRNA is found in human fetal erythroid tissue but not in adult erythroid or other nonerythroid tissue. The theta-1 gene may be expressed very early in embryonic life, perhaps sometime before 5 weeks. Theta-1 is a member of the human alpha-globin gene cluster that involves five functional genes and two pseudogenes. The order of genes is: 5’ - zeta - pseudozeta - mu - pseudoalpha-2 -pseudoalpha-1 - alpha-2 - alpha-1 - theta-1 - 3’. Research supports a transcriptionally active role for the gene and a functional role for the peptide in specific cells, possibly those of early erythroid tissue.

Source: NCBI Gene 3049 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 27 total — 1 pathogenic
• MANE Select transcript: NM_005331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4833
Approved symbol	HBQ1
Name	hemoglobin subunit theta 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HBQ
Ensembl gene	ENSG00000086506
Ensembl biotype	protein_coding
OMIM	142240
Entrez	3049

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000199708

RefSeq mRNA: 1 — MANE Select: NM_005331 NM_005331

CCDS: CCDS10400

Canonical transcript exons

ENST00000199708 — 3 exons

Exon	Start	End
ENSE00000663730	180980	181179
ENSE00001118463	180459	180581
ENSE00001769246	180666	180870

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 90.49.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7202 / max 168.6941, expressed in 354 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151870	2.7202	354

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	90.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.57	gold quality
monocyte	CL:0000576	84.54	gold quality
mononuclear cell	CL:0000842	84.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.21	gold quality
leukocyte	CL:0000738	82.90	gold quality
trabecular bone tissue	UBERON:0002483	82.27	gold quality
anterior cingulate cortex	UBERON:0009835	76.92	gold quality
cingulate cortex	UBERON:0003027	76.80	gold quality
nucleus accumbens	UBERON:0001882	75.55	gold quality
bone marrow	UBERON:0002371	74.91	gold quality
amygdala	UBERON:0001876	74.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.48	gold quality
right frontal lobe	UBERON:0002810	72.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	72.46	gold quality
granulocyte	CL:0000094	72.24	gold quality
caudate nucleus	UBERON:0001873	70.53	gold quality
putamen	UBERON:0001874	67.40	gold quality
cortical plate	UBERON:0005343	65.51	gold quality
hypothalamus	UBERON:0001898	65.01	gold quality
bone marrow cell	CL:0002092	64.49	gold quality
telencephalon	UBERON:0001893	64.36	gold quality
tendon of biceps brachii	UBERON:0008188	63.69	gold quality
forebrain	UBERON:0001890	62.92	gold quality
cerebral cortex	UBERON:0000956	62.83	gold quality
temporal lobe	UBERON:0001871	62.68	gold quality
neocortex	UBERON:0001950	62.04	gold quality
Ammon’s horn	UBERON:0001954	61.47	gold quality
vena cava	UBERON:0004087	61.45	gold quality
brain	UBERON:0000955	60.99	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	144.62
E-HCAD-4	yes	142.80
E-CURD-112	yes	51.46
E-MTAB-10042	yes	44.71
E-MTAB-9221	yes	17.99
E-HCAD-9	yes	10.79
E-MTAB-9388	yes	9.44
E-MTAB-9067	yes	7.23
E-ANND-3	yes	7.14
E-HCAD-10	yes	6.81
E-MTAB-9467	yes	3.88

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• 2 new Spanish alpha-thalassemia mutations were found. In both mutations, both alpha genes were deleted, the gene theta; and the region HS40. (PMID:21453942)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hbq1a	ENSMUSG00000020295
mus_musculus	Hbq1b	ENSMUSG00000073063
rattus_norvegicus		ENSRNOG00000070249
rattus_norvegicus		ENSRNOG00000074159
rattus_norvegicus		ENSRNOG00000087981
drosophila_melanogaster	glob1	FBGN0027657
caenorhabditis_elegans		WBGENE00008996
caenorhabditis_elegans		WBGENE00077763

Paralogs (11): HBZ (ENSG00000130656), CYGB (ENSG00000161544), HBA2 (ENSG00000188536), HBG2 (ENSG00000196565), MB (ENSG00000198125), HBA1 (ENSG00000206172), HBM (ENSG00000206177), HBE1 (ENSG00000213931), HBG1 (ENSG00000213934), HBD (ENSG00000223609), HBB (ENSG00000244734)

Protein

Protein identifiers

Hemoglobin subunit theta-1 — P09105 (reviewed: P09105)

Alternative names: Hemoglobin theta-1 chain, Theta-1-globin

All UniProt accessions (2): P09105, A0A1K0GUV5

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the globin family.

RefSeq proteins (1): NP_005322* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000971	Globin	Domain
IPR002338	Hemoglobin_a-typ	Family
IPR002339	Hemoglobin_pi	Family
IPR009050	Globin-like_sf	Homologous_superfamily
IPR012292	Globin/Proto	Homologous_superfamily
IPR050056	Hemoglobin_oxygen_transport	Family

Pfam: PF00042

UniProt features (4 total): binding site 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09105-F1	96.59	0.97

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): 59 (distal binding residue); 88 (proximal binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GNF2_PRDX2, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_ERYTHROCYTE_HOMEOSTASIS, GNF2_ANK1, GOBP_GAS_TRANSPORT, GOBP_OXYGEN_TRANSPORT, GNF2_SPTA1, GNF2_PCAF, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOMF_OXYGEN_BINDING, GOBP_ERYTHROCYTE_DEVELOPMENT, GNF2_MAP2K3, GOBP_HOMEOSTATIC_PROCESS

GO Biological Process (2): oxygen transport (GO:0015671), erythrocyte development (GO:0048821)

GO Molecular Function (6): oxygen carrier activity (GO:0005344), iron ion binding (GO:0005506), oxygen binding (GO:0019825), heme binding (GO:0020037), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): hemoglobin complex (GO:0005833), haptoglobin-hemoglobin complex (GO:0031838)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein-containing complex	2
gas transport	1
erythrocyte differentiation	1
myeloid cell development	1
oxygen transport	1
oxygen binding	1
molecular carrier activity	1
transition metal ion binding	1
small molecule binding	1
tetrapyrrole binding	1
binding	1
cation binding	1
cytosol	1

Protein interactions and networks

STRING

530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HBQ1	LUC7L	Q9NQ29	856
HBQ1	NPRL3	Q12980	546
HBQ1	HBE1	P02100	502
HBQ1	HPRT1	P00492	497
HBQ1	AHSP	Q9NZD4	473
HBQ1	HBD	P02042	465
HBQ1	EPB42	P16452	453
HBQ1	ALAS2	P22557	451
HBQ1	UTY	O14607	442
HBQ1	STEAP4	Q687X5	438
HBQ1	FAM234A	Q9H0X4	432
HBQ1	HBB	P02023	431
HBQ1	HBZ	P02008	428
HBQ1	GUF1	Q8N442	423
HBQ1	FECH	P22830	416

IntAct

44 interactions, top by confidence:

A	B	Type	Score
HBQ1	RFESD	psi-mi:“MI:0915”(physical association)	0.780
HBD	HBQ1	psi-mi:“MI:0915”(physical association)	0.720
HBQ1	HBD	psi-mi:“MI:0915”(physical association)	0.720
AHCYL1	HBQ1	psi-mi:“MI:0915”(physical association)	0.600
HBQ1	HBA1	psi-mi:“MI:0915”(physical association)	0.560
HBQ1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
HBQ1	HBG2	psi-mi:“MI:0915”(physical association)	0.560
HBZ	HBQ1	psi-mi:“MI:0915”(physical association)	0.560
HBQ1	HBB	psi-mi:“MI:0915”(physical association)	0.560
HBE1	HBQ1	psi-mi:“MI:0915”(physical association)	0.560
NIF3L1	HBQ1	psi-mi:“MI:0915”(physical association)	0.560
HBQ1	IGLL5	psi-mi:“MI:0914”(association)	0.350
HBQ1	FASN	psi-mi:“MI:0914”(association)	0.350
CDKN2D	HBQ1	psi-mi:“MI:0914”(association)	0.350
RFESD	HBQ1	psi-mi:“MI:0915”(physical association)	0.000
AHCYL1	HBQ1	psi-mi:“MI:0915”(physical association)	0.000
HBQ1	HBA1	psi-mi:“MI:0915”(physical association)	0.000
NTAQ1	HBQ1	psi-mi:“MI:0915”(physical association)	0.000
HBG2	HBQ1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): HBQ1 (Two-hybrid), RFESD (Two-hybrid), HBZ (Two-hybrid), WDYHV1 (Two-hybrid), AHCYL1 (Two-hybrid), RFESD (Two-hybrid), HBA2 (Two-hybrid), HBG2 (Two-hybrid), HBA1 (Two-hybrid), HBE1 (Two-hybrid), HBD (Two-hybrid), HBB (Two-hybrid), ZG16B (Affinity Capture-MS), PIGR (Affinity Capture-MS), FASN (Affinity Capture-MS)

ESM2 similar proteins: A1A4Q3, B0M2T2, O12985, P01998, P02000, P02005, P02006, P02112, P02113, P02115, P02116, P02117, P02118, P02120, P02121, P02122, P02123, P02124, P02126, P06714, P06890, P07036, P07406, P07411, P08851, P09105, P0C0U7, P10058, P10062, P10781, P11896, P14261, P14523, P14524, P21668, P22742, P30893, P68061, P68062, P68063

Diamond homologs: B3EWE3, D0VX09, P01923, P01924, P01926, P01928, P01929, P01930, P01934, P01935, P01937, P01938, P01939, P01940, P01941, P01948, P01951, P01953, P01956, P01958, P01959, P01960, P01961, P01962, P01963, P01964, P01965, P01966, P01967, P01971, P01973, P04237, P06635, P06714, P06890, P07402, P07405, P07421, P07425, P08258

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 13 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.

GO biological processes:

GO term	Partners	Fold	FDR
oxygen transport	6	526.6×	6e-15
erythrocyte development	6	263.3×	5e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
144341	GRCh38/hg38 16p13.3(chr16:180542-181197)x1	Pathogenic

SpliceAI

178 predictions. Top by Δscore:

Variant	Effect	Δscore
16:180578:A:T	donor_gain	1.0000
16:180578:AAAGG:A	donor_loss	0.9900
16:180581:GGT:G	donor_loss	0.9900
16:180583:T:A	donor_loss	0.9900
16:180660:TCGCA:T	acceptor_loss	0.9900
16:180662:GCAG:G	acceptor_loss	0.9900
16:180663:CA:C	acceptor_loss	0.9900
16:180664:A:AG	acceptor_gain	0.9900
16:180665:G:GG	acceptor_gain	0.9900
16:180867:CCAGG:C	donor_loss	0.9900
16:180868:CAGGT:C	donor_loss	0.9900
16:180870:GGT:G	donor_loss	0.9900
16:180871:G:GA	donor_loss	0.9900
16:180872:T:G	donor_loss	0.9900
16:180664:AG:A	acceptor_gain	0.9800
16:180665:GG:G	acceptor_gain	0.9800
16:180665:GGACC:G	acceptor_gain	0.9800
16:180665:GGA:G	acceptor_gain	0.9700
16:180665:GGAC:G	acceptor_gain	0.9700
16:180710:T:TA	acceptor_gain	0.9500
16:180577:G:GT	donor_gain	0.9300
16:180591:GC:G	donor_gain	0.9000
16:180661:C:CA	acceptor_gain	0.8900
16:180871:G:GG	donor_gain	0.8800
16:180999:T:A	acceptor_gain	0.8600
16:180978:A:AG	acceptor_gain	0.8500
16:180979:G:GG	acceptor_gain	0.8500
16:180582:G:GG	donor_gain	0.8400
16:181024:C:CA	acceptor_gain	0.8300
16:181026:G:C	acceptor_gain	0.8200

AlphaMissense

895 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:180679:T:C	F37L	0.923
16:180681:C:A	F37L	0.923
16:180681:C:G	F37L	0.923
16:180700:T:C	F44L	0.920
16:180702:C:A	F44L	0.920
16:180702:C:G	F44L	0.920
16:181064:T:C	F129L	0.901
16:181066:C:A	F129L	0.901
16:181066:C:G	F129L	0.901
16:180865:T:C	F99L	0.881
16:180867:C:A	F99L	0.881
16:180867:C:G	F99L	0.881
16:180529:T:A	W15R	0.861
16:180529:T:C	W15R	0.861
16:180994:C:G	C105W	0.853
16:180571:G:C	A29P	0.839
16:180749:G:A	G60D	0.837
16:180666:G:C	R32S	0.834
16:180666:G:T	R32S	0.834
16:181065:T:C	F129S	0.829
16:180701:T:C	F44S	0.822
16:180572:C:A	A29D	0.821
16:180760:G:C	A64P	0.817
16:181077:T:A	V133D	0.806
16:180766:G:C	A66P	0.804
16:180563:C:A	T26K	0.797
16:180531:G:C	W15C	0.795
16:180531:G:T	W15C	0.795
16:180992:T:C	C105R	0.790
16:180761:C:A	A64E	0.785

dbSNP variants (sampled 300 via entrez): RS1000984958 (16:181378 A>G), RS1002414361 (16:178924 CA>C,CAA), RS1002672675 (16:179716 A>G), RS1002747324 (16:178719 G>A,C), RS1002823969 (16:181088 C>G), RS1003158228 (16:180073 G>A,T), RS1004026578 (16:180466 G>A,C), RS1004241607 (16:180261 C>T), RS1004343642 (16:180879 C>G,T), RS1004356061 (16:180694 A>G), RS1004908099 (16:179598 T>A), RS1005364 (16:180482 C>A,G,T), RS1005436369 (16:179310 G>A), RS1006866651 (16:179404 A>C), RS1007202789 (16:179177 C>T)

Disease associations

OMIM: gene MIM:142240 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST003122_1	Hemoglobin levels	6.000000e-18
GCST004601_134	Red blood cell count	7.000000e-31
GCST004602_220	Mean corpuscular volume	1.000000e-85
GCST004605_10	Mean corpuscular hemoglobin concentration	3.000000e-52
GCST004619_59	Reticulocyte fraction of red cells	4.000000e-11
GCST004630_168	Mean corpuscular hemoglobin	2.000000e-12
GCST004630_169	Mean corpuscular hemoglobin	1.000000e-109
GCST010083_266	Hemoglobin levels	2.000000e-16
GCST90002384_354	Hemoglobin	1.000000e-24
GCST90002386_276	High light scatter reticulocyte percentage of red cells	1.000000e-27
GCST90002390_630	Mean corpuscular hemoglobin	2.000000e-214
GCST90002391_159	Mean corpuscular hemoglobin concentration	3.000000e-09
GCST90002391_160	Mean corpuscular hemoglobin concentration	4.000000e-90
GCST90002392_476	Mean corpuscular volume	3.000000e-179
GCST90002396_645	Mean reticulocyte volume	4.000000e-12
GCST90002397_273	Mean spheric corpuscular volume	5.000000e-37
GCST90002403_657	Red blood cell count	4.000000e-119
GCST90002404_332	Red cell distribution width	1.000000e-32
GCST90002406_402	Reticulocyte fraction of red cells	2.000000e-49

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0007629	hemoglobin A1 measurement
EFO:0004305	erythrocyte count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
propionaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
perfluorobutyric acid	increases expression	1
pentanal	increases expression	1
tebuconazole	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Tunicamycin	decreases expression	1
Urethane	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Sodium Selenite	decreases expression	1
Thapsigargin	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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