HBM

Summary

HBM (hemoglobin subunit mu, HGNC:4826) is a protein-coding gene on chromosome 16p13.3, encoding Hemoglobin subunit mu (Q6B0K9).

The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5’- zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta - 3’. This gene has an ORF encoding a 141 aa polypeptide which is similar to the delta globins found in reptiles and birds. This locus was originally described as a pseudogene; however, it is currently thought to be a protein-coding gene.

Source: NCBI Gene 3042 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 27 total — 1 pathogenic
• MANE Select transcript: NM_001003938

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4826
Approved symbol	HBM
Name	hemoglobin subunit mu
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HBK
Ensembl gene	ENSG00000206177
Ensembl biotype	protein_coding
OMIM	609639
Entrez	3042

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000356815, ENST00000472539, ENST00000496585

RefSeq mRNA: 1 — MANE Select: NM_001003938 NM_001003938

CCDS: CCDS32347

Canonical transcript exons

ENST00000356815 — 3 exons

Exon	Start	End
ENSE00001410869	166580	166764
ENSE00001494261	165978	166089
ENSE00003624064	166268	166472

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 99.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 21.7970 / max 11188.1430, expressed in 116 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151859	21.7970	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.86	gold quality
bone marrow	UBERON:0002371	97.23	gold quality
blood	UBERON:0000178	96.66	gold quality
bone marrow cell	CL:0002092	95.86	gold quality
monocyte	CL:0000576	91.01	gold quality
leukocyte	CL:0000738	86.44	gold quality
placenta	UBERON:0001987	77.13	gold quality
amniotic fluid	UBERON:0000173	73.64	silver quality
spleen	UBERON:0002106	69.24	gold quality
biceps brachii	UBERON:0001507	67.42	silver quality
endothelial cell	CL:0000115	66.17	silver quality
ganglionic eminence	UBERON:0004023	61.68	gold quality
decidua	UBERON:0002450	61.58	silver quality
apex of heart	UBERON:0002098	60.88	gold quality
cortical plate	UBERON:0005343	58.59	gold quality
deltoid	UBERON:0001476	57.02	gold quality
lower esophagus mucosa	UBERON:0035834	57.01	gold quality
metanephros	UBERON:0000081	56.55	gold quality
bronchial epithelial cell	CL:0002328	56.42	silver quality
cartilage tissue	UBERON:0002418	56.24	gold quality
pancreatic ductal cell	CL:0002079	56.15	silver quality
bronchus	UBERON:0002185	55.67	silver quality
tendon of biceps brachii	UBERON:0008188	54.39	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
epithelial cell of pancreas	CL:0000083	54.18	gold quality
right lobe of liver	UBERON:0001114	53.93	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
adrenal tissue	UBERON:0018303	53.85	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	14616.42
E-HCAD-4	yes	8855.62
E-MTAB-7407	yes	8311.98
E-CURD-112	yes	7145.59
E-GEOD-124472	yes	3768.70
E-CURD-98	yes	1746.72
E-ANND-5	yes	885.91
E-MTAB-9221	yes	26.89
E-HCAD-9	yes	13.85
E-MTAB-9067	yes	11.77
E-MTAB-9467	yes	9.45
E-MTAB-9388	yes	9.34
E-HCAD-10	yes	7.84
E-GEOD-75367	no	4838.43
E-CURD-126	no	222.71

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• results suggest the human genome encodes a previously unrecognized globin member of the avian alpha-D family that is transcribed in a highly regulated pattern in erythroid cells (PMID:15855277)
• HbM Saskatoon is normally a harmless variant. However, in conjunction with severe pneumonia, we assume that it did not only affect clinical evaluation, but also exacerbated pneumonia by reducing the oxygen binding capacity. (PMID:19199228)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
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), HBE1 (ENSG00000213931), HBG1 (ENSG00000213934), HBD (ENSG00000223609), HBB (ENSG00000244734)

Protein

Protein identifiers

Hemoglobin subunit mu — Q6B0K9 (reviewed: Q6B0K9)

Alternative names: Hemoglobin mu chain, Mu-globin

All UniProt accessions (2): A0A1K0FU50, Q6B0K9

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in erythroid tissues.

Similarity. Belongs to the globin family.

RefSeq proteins (1): NP_001003938* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000971	Globin	Domain
IPR002338	Hemoglobin_a-typ	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)

1 structures.

PDB	Method	Resolution (Å)
9IUX	X-RAY DIFFRACTION	1.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6B0K9-F1	95.79	0.92

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): 58 (distal binding residue); 87 (proximal binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 43 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_GAS_TRANSPORT, GOBP_OXYGEN_TRANSPORT, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOMF_OXYGEN_BINDING, GOBP_ERYTHROCYTE_DEVELOPMENT, GOBP_HOMEOSTATIC_PROCESS, GOCC_HEMOGLOBIN_COMPLEX, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GOBP_HOMEOSTASIS_OF_NUMBER_OF_CELLS, GOMF_TETRAPYRROLE_BINDING, GOCC_HAPTOGLOBIN_HEMOGLOBIN_COMPLEX

GO Biological Process (2): 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), metal ion binding (GO:0046872), protein binding (GO:0005515)

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
small molecule binding	1
tetrapyrrole binding	1
cation binding	1
binding	1
cytosol	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HBM	MAP4K5	Q9Y4K4	477
HBM	IGFLR1	Q9H665	447
HBM	TTK	P33981	424
HBM	NRDE2	Q9H7Z3	407
HBM	SCRN3	Q0VDG4	377
HBM	ALAS2	P22557	356
HBM	QRFPR	Q96P65	328
HBM	PRG3	Q9Y2Y8	326
HBM	EPB42	P16452	320
HBM	TSPO2	Q5TGU0	316
HBM	NGB	Q9NPG2	314
HBM	CARNS1	A5YM72	310
HBM	MRE11	P49959	306
HBM	RAC3	P60763	301
HBM	KCNMA1	Q12791	288

IntAct

21 interactions, top by confidence:

A	B	Type	Score
HBM	TRAF2	psi-mi:“MI:0915”(physical association)	0.560
HBM	HBB	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	HBM	psi-mi:“MI:0915”(physical association)	0.560
HBZ	HBM	psi-mi:“MI:0915”(physical association)	0.560
HBG2	HBM	psi-mi:“MI:0915”(physical association)	0.560
HBB	HBM	psi-mi:“MI:0915”(physical association)	0.560
VIRMA	HBM	psi-mi:“MI:0915”(physical association)	0.560
HBM	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
HBM	HBZ	psi-mi:“MI:0915”(physical association)	0.000
HBM	HBG2	psi-mi:“MI:0915”(physical association)	0.000
HBM	VIRMA	psi-mi:“MI:0915”(physical association)	0.000
HBG2	HBM	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): MUC5B (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), BPIFB1 (Affinity Capture-MS), MUC5AC (Affinity Capture-MS), IGHA2 (Affinity Capture-MS), LTF (Affinity Capture-MS), BPIFA1 (Affinity Capture-MS), PIGR (Affinity Capture-MS), PRR4 (Affinity Capture-MS), LACRT (Affinity Capture-MS), IGJ (Affinity Capture-MS), IGKC (Affinity Capture-MS), CST1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), CST4 (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: A1A4Q3, B3EWD1, B3EWE1, B3EWE3, O12985, P01942, P01943, P01944, P01945, P01946, P01947, P01950, P01964, P01967, P01975, P01977, P01978, P01979, P01980, P01983, P01990, P01993, P02001, P02002, P02003, P02005, P02006, P02007, P02008, P02009, P02011, P04237, P04238, P04239, P04240, P04241, P04242, P04243, P04442, P06347

SIGNOR signaling

0 interactions.

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	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
38633	NG_000006.1:g.24664_41064del16401	Pathogenic

SpliceAI

379 predictions. Top by Δscore:

Variant	Effect	Δscore
16:153945:ACCCG:A	acceptor_gain	1.0000
16:154093:CAAG:C	donor_loss	1.0000
16:154094:AAGG:A	donor_loss	1.0000
16:154095:AG:A	donor_gain	1.0000
16:154095:AGGT:A	donor_loss	1.0000
16:154096:GG:G	donor_gain	1.0000
16:154097:GTGC:G	donor_loss	1.0000
16:166472:GGTG:G	donor_loss	1.0000
16:166473:G:GG	donor_gain	1.0000
16:153945:ACCC:A	acceptor_gain	0.9900
16:154097:G:GG	donor_gain	0.9900
16:154270:A:AG	acceptor_gain	0.9900
16:154271:G:GG	acceptor_gain	0.9900
16:166085:CTCAG:C	donor_loss	0.9900
16:166086:TCAG:T	donor_loss	0.9900
16:166088:AG:A	donor_loss	0.9900
16:166089:GG:G	donor_loss	0.9900
16:166090:GT:G	donor_loss	0.9900
16:166091:T:G	donor_loss	0.9900
16:166266:A:AG	acceptor_gain	0.9900
16:166267:G:GG	acceptor_gain	0.9900
16:166468:TTCCG:T	donor_gain	0.9900
16:166576:GCAG:G	acceptor_loss	0.9900
16:166577:CAG:C	acceptor_loss	0.9900
16:166578:A:AC	acceptor_loss	0.9900
16:166578:A:AG	acceptor_gain	0.9900
16:166578:AGCT:A	acceptor_gain	0.9900
16:166579:G:GG	acceptor_gain	0.9900
16:166579:G:GT	acceptor_loss	0.9900
16:166579:GC:G	acceptor_gain	0.9900

AlphaMissense

912 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:166655:T:A	W125R	0.965
16:166655:T:C	W125R	0.965
16:166594:T:G	C104W	0.953
16:166302:T:C	F43L	0.947
16:166304:C:A	F43L	0.947
16:166304:C:G	F43L	0.947
16:166592:T:C	C104R	0.944
16:166631:T:C	F117L	0.943
16:166633:C:A	F117L	0.943
16:166633:C:G	F117L	0.943
16:166467:T:C	F98L	0.941
16:166469:T:A	F98L	0.941
16:166469:T:G	F98L	0.941
16:166665:T:C	F128S	0.939
16:166468:T:G	F98C	0.938
16:166468:T:C	F98S	0.936
16:166664:T:C	F128L	0.925
16:166666:C:A	F128L	0.925
16:166666:C:G	F128L	0.925
16:166089:G:T	R31M	0.922
16:166303:T:C	F43S	0.920
16:166037:T:A	W14R	0.917
16:166037:T:C	W14R	0.917
16:166268:G:C	R31S	0.915
16:166268:G:T	R31S	0.915
16:166632:T:C	F117S	0.898
16:166303:T:G	F43C	0.896
16:166089:G:C	R31T	0.893
16:166039:G:C	W14C	0.892
16:166039:G:T	W14C	0.892

dbSNP variants (sampled 300 via entrez): RS1001322703 (16:165736 G>T), RS1001690336 (16:165535 C>T), RS1003634449 (16:166817 G>A), RS1005499944 (16:165478 G>A,T), RS1005887848 (16:165784 C>A,T), RS1006293917 (16:165602 G>A), RS1006718059 (16:166245 C>A,G), RS1007832757 (16:165209 C>G), RS1008131442 (16:165374 T>A,C), RS1009617539 (16:165049 G>T), RS1011181694 (16:167153 C>G), RS1012354323 (16:166759 G>A,C,T), RS1013776089 (16:165812 C>T), RS1016763664 (16:166554 C>A,G,T), RS1017554541 (16:166285 C>G)

Disease associations

OMIM: gene MIM:609639 | disease phenotypes: MIM:604131

GenCC curated gene-disease

Mondo (1): alpha thalassemia spectrum (MONDO:0011399)

Orphanet (1): Alpha-thalassemia (Orphanet:846)

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST003122_1	Hemoglobin levels	6.000000e-18
GCST004335_16	Mean corpuscular volume	6.000000e-12
GCST004602_219	Mean corpuscular volume	8.000000e-15
GCST004628_13	Immature fraction of reticulocytes	4.000000e-09
GCST004630_167	Mean corpuscular hemoglobin	1.000000e-33
GCST005951_12	Body mass index	5.000000e-11
GCST008034_20	Hemoglobin A1c levels	8.000000e-12
GCST008034_9	Hemoglobin A1c levels	3.000000e-12
GCST008398_14	Glycated hemoglobin levels	1.000000e-09
GCST90002384_352	Hemoglobin	2.000000e-12
GCST90002385_64	High light scatter reticulocyte count	3.000000e-13
GCST90002385_65	High light scatter reticulocyte count	5.000000e-13
GCST90002386_604	High light scatter reticulocyte percentage of red cells	2.000000e-17
GCST90002387_11	Immature fraction of reticulocytes	5.000000e-17
GCST90002390_625	Mean corpuscular hemoglobin	2.000000e-37
GCST90002390_626	Mean corpuscular hemoglobin	6.000000e-17
GCST90002390_628	Mean corpuscular hemoglobin	1.000000e-11
GCST90002392_474	Mean corpuscular volume	1.000000e-46
GCST90002403_656	Red blood cell count	1.000000e-17
GCST90002404_331	Red cell distribution width	8.000000e-30
GCST90002405_348	Reticulocyte count	2.000000e-13
GCST90002406_398	Reticulocyte fraction of red cells	1.000000e-17
GCST90002406_399	Reticulocyte fraction of red cells	8.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0007629	hemoglobin A1 measurement
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004340	body mass index
EFO:0004541	HbA1c measurement
EFO:0004305	erythrocyte count
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D017085	alpha-Thalassemia	C15.378.050.141.150.875.100; C15.378.420.826.100; C16.320.070.875.100; C16.320.365.826.100

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
tetrabromobisphenol A	decreases expression	1
hydroquinone	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	increases abundance, decreases methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02986698	PHASE1	TERMINATED	In Utero Hematopoietic Stem Cell Transplantation for Alpha-thalassemia Major (ATM)
NCT01419704	PHASE1/PHASE2	WITHDRAWN	Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
NCT00159029	Not specified	COMPLETED	Genetics of Alpha Thalassemia in Israeli Ethnic Groups
NCT02692872	Not specified	ACTIVE_NOT_RECRUITING	Screening for Alpha Thalassemia in Healthy Volunteers
NCT04872179	Not specified	RECRUITING	International Registry of Patients With Alpha Thalassemia
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06539169	Not specified	RECRUITING	FLOWER: Following Longitudinal Outcomes With Epidemiology for Rare Diseases
NCT06591936	Not specified	RECRUITING	Genetic Profile of Alpha Thalassemia Children at Sohag University Hospital .
NCT06831799	Not specified	COMPLETED	ERN-EuroBloodNet Registry on Patients With Rare Red Blood Cell Defects and COVID-19