HMHB1

Summary

HMHB1 (histocompatibility minor HB-1, HGNC:29677) is a protein-coding gene on chromosome 5q31.3, encoding Minor histocompatibility protein HB-1 (O97980). Precursor of the histocomplatibility antigen HB-1.

This gene encodes one of the minor histocompatibility antigens, which play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). This gene is only expressed in B cell acute lymphoblastic leukemia cells and Epstein-Barr virus-transformed B cells. The translation of this mRNA initiates at a non-AUG (CUG) codon.

Source: NCBI Gene 57824 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_021182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29677
Approved symbol	HMHB1
Name	histocompatibility minor HB-1
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	HB-1, HB-1Y
Ensembl gene	ENSG00000158497
Ensembl biotype	protein_coding
OMIM	609961
Entrez	57824

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000289448, ENST00000850872

RefSeq mRNA: 1 — MANE Select: NM_021182 NM_021182

CCDS: CCDS43376

Canonical transcript exons

ENST00000289448 — 2 exons

Exon	Start	End
ENSE00004282580	143812161	143812304
ENSE00004282582	143820480	143820716

Expression profiles

Bgee: expression breadth broad, 83 present calls, max score 88.50.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.50	gold quality
endometrium epithelium	UBERON:0004811	83.84	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.93	gold quality
paraflocculus	UBERON:0005351	76.83	silver quality
middle frontal gyrus	UBERON:0002702	76.03	silver quality
Brodmann (1909) area 10	UBERON:0013541	63.01	gold quality
triceps brachii	UBERON:0001509	61.44	gold quality
gluteal muscle	UBERON:0002000	61.10	gold quality
pancreatic ductal cell	CL:0002079	60.63	silver quality
tendon of biceps brachii	UBERON:0008188	57.08	gold quality
decidua	UBERON:0002450	56.96	gold quality
vena cava	UBERON:0004087	55.93	gold quality
quadriceps femoris	UBERON:0001377	55.34	gold quality
tibialis anterior	UBERON:0001385	54.80	silver quality
thymus	UBERON:0002370	54.68	gold quality
bone marrow	UBERON:0002371	54.42	gold quality
vastus lateralis	UBERON:0001379	53.99	gold quality
deltoid	UBERON:0001476	53.55	silver quality
ileal mucosa	UBERON:0000331	53.33	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
bone marrow cell	CL:0002092	52.11	silver quality
buccal mucosa cell	CL:0002336	50.82	gold quality
cranial nerve II	UBERON:0000941	50.64	silver quality
layer of synovial tissue	UBERON:0007616	49.92	gold quality
myocardium	UBERON:0002349	49.64	gold quality
metanephric glomerulus	UBERON:0004736	49.59	gold quality
oviduct epithelium	UBERON:0004804	49.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	4.53
E-ANND-3	no	1.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting HMHB1, 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-590-3P	99.96	74.34	6478
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4761-3P	96.27	66.26	524

Literature-anchored findings (GeneRIF, showing 2)

• Improved genotyping of the human minor histocompatibility antigen HB-1 by polymerase chain reaction with sequence-specific primers using a complementary oligonucleotide. (PMID:20718936)
• The paper described that non-AUG (CTG) translation initiation codon at nucleotide positions 108-110 was used for the encoded protein. (PMID:9892612)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Minor histocompatibility protein HB-1 — O97980 (reviewed: O97980)

All UniProt accessions (2): A0A1X7SBT3, O97980

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of the histocomplatibility antigen HB-1. More generally, minor histocomplatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocomplatibility antigen in HLA-matched sibling marrow transplants. HB-1 is presented on the cell surface by MHC class I HLA-B44. This complex specifically elicits donor-cytotoxic T lymphocyte (CTL) reactivity in B-cell acute lymphoblastic leukemia (B-ALL) after treatment by HLA-identical allogenic bone marrow transplantation (BMT). It induces cell recognition and lysis by CTL. However, HB-1 restricted expression in B-ALL cells and not in normal tissues may allow a specific CTL reactivity against B-ALL without the risk of evoking graft-versus-host disease.

Subunit / interactions. HB-1 forms a complex with MHC class I HLA-B44.

Tissue specificity. Expressed in acute lymphoblastic leukemia B-cells and Epstein-Barr virus-transformed B-cells.

RefSeq proteins (1): NP_067005* (*=MANE)

Domains & families (InterPro)

UniProt features (15 total): mutagenesis site 11, chain 1, peptide 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O97980-F1	72.37	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (11):

Position	Phenotype
15	complete loss of ctl recognition.
16	complete loss of ctl recognition.
16	ctl recognition.
17	decreased ctl recognition.
18	complete loss of ctl recognition.
9	decreased ctl recognition.
10	decreased ctl recognition.
11	complete loss of ctl recognition.
12	complete loss of ctl recognition.
13	complete loss of ctl recognition.
14	complete loss of ctl recognition.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 50 (showing top): GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, MODULE_379, GOBP_CYTOKINE_PRODUCTION, GOBP_ADAPTIVE_IMMUNE_RESPONSE, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, MODULE_242, GOBP_POSITIVE_REGULATION_OF_TYPE_II_INTERFERON_PRODUCTION, GOBP_RESPONSE_TO_TUMOR_NECROSIS_FACTOR, GOBP_POSITIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, MODULE_104, chr5q31, DIAZ_CHRONIC_MYELOGENOUS_LEUKEMIA_DN, MORF_PAX7, MORF_TNFRSF25

GO Biological Process (5): adaptive immune response (GO:0002250), regulation of gene expression (GO:0010468), positive regulation of type II interferon production (GO:0032729), cellular response to tumor necrosis factor (GO:0071356), immune system process (GO:0002376)

GO Molecular Function (0):

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	1
gene expression	1
regulation of macromolecule biosynthetic process	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
response to tumor necrosis factor	1
cellular response to cytokine stimulus	1
biological_process	1

Protein interactions and networks

STRING

148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMHB1	MYO1G	B0I1T2	571
HMHB1	PLAC8L1	A1L4L8	506
HMHB1	GRXCR2	A6NFK2	401
HMHB1	ARHGAP45	Q92619	396
HMHB1	HMSD	A8MTL9	394
HMHB1	RESF1	Q9HCM1	360
HMHB1	GPR151	Q8TDV0	356
HMHB1	PRELID2	Q8N945	353
HMHB1	SH3RF2	Q8TEC5	348
HMHB1	CENPM	Q9NSP4	336
HMHB1	QTMAN	Q4AE62	336
HMHB1	KCTD16	Q68DU8	324
HMHB1	RFLNB	Q8N5W9	323
HMHB1	YIPF5	Q969M3	315
HMHB1	Q3LFD5	Q3LFD5	314

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GVK7, A6ZT44, A7RHB3, C0H3T6, G2TRJ6, G3UWD5, H3BU77, J3QM76, O14183, O29949, O74506, O97980, P0CT00, P0CT01, P0DXN9, P15960, P22384, P25575, P27975, P27982, P36340, P38839, P42172, P50628, P68353, P80594, P92538, P93301, Q00147, Q10486, Q14236, Q16048, Q1X6Y7, Q1X6Z0, Q32P96, Q3E795, Q3E7K4, Q3V4X0, Q495D7, Q5K130

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

214 predictions. Top by Δscore:

Variant	Effect	Δscore
5:143812302:GAG:G	donor_gain	1.0000
5:143812301:AGAGG:A	donor_loss	0.9900
5:143812302:G:GT	donor_gain	0.9900
5:143812302:GAGG:G	donor_loss	0.9900
5:143812303:AGGTG:A	donor_loss	0.9900
5:143812305:GTGA:G	donor_loss	0.9900
5:143812306:T:G	donor_loss	0.9900
5:143814237:G:GT	donor_gain	0.9900
5:143814238:A:T	donor_gain	0.9700
5:143812305:G:GG	donor_gain	0.9400
5:143813905:C:T	donor_gain	0.9300
5:143812301:AGAG:A	donor_gain	0.9200
5:143813904:GCAAA:G	donor_gain	0.9200
5:143820474:CTATA:C	acceptor_loss	0.9200
5:143820475:TATA:T	acceptor_loss	0.9200
5:143820477:TAGGT:T	acceptor_loss	0.9200
5:143820478:AGGTT:A	acceptor_loss	0.9200
5:143820479:G:A	acceptor_loss	0.9200
5:143812292:G:GT	donor_gain	0.9000
5:143812310:G:GT	donor_gain	0.8800
5:143812300:AAGAG:A	donor_gain	0.8600
5:143820469:CTTTT:C	acceptor_loss	0.8400
5:143820478:A:AG	acceptor_gain	0.8100
5:143820479:G:GG	acceptor_gain	0.8100
5:143813908:A:G	donor_gain	0.8000
5:143814653:A:AG	donor_gain	0.7900
5:143820466:ATTCT:A	acceptor_loss	0.7700
5:143820467:TTCTT:T	acceptor_loss	0.7700
5:143820468:TCTTT:T	acceptor_loss	0.7700
5:143820470:TTTTC:T	acceptor_loss	0.7600

AlphaMissense

261 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:143820492:T:A	V17D	0.899
5:143820499:G:C	K19N	0.862
5:143820499:G:T	K19N	0.862
5:143820496:G:C	W18C	0.815
5:143820496:G:T	W18C	0.815
5:143820538:G:C	R32S	0.805
5:143820538:G:T	R32S	0.805
5:143820542:A:C	S34R	0.788
5:143820544:C:A	S34R	0.788
5:143820544:C:G	S34R	0.788
5:143820525:A:T	D28V	0.761
5:143820492:T:C	V17A	0.760
5:143820498:A:C	K19T	0.734
5:143820524:G:C	D28H	0.734
5:143820537:G:T	R32M	0.734
5:143820504:A:T	E21V	0.733
5:143820492:T:G	V17G	0.731
5:143820498:A:T	K19M	0.726
5:143820507:T:C	L22S	0.720
5:143820500:T:C	S20P	0.708
5:143820501:C:G	S20W	0.708
5:143820510:T:A	V23D	0.705
5:143820522:A:T	D27V	0.704
5:143820494:T:A	W18R	0.693
5:143820494:T:C	W18R	0.693
5:143820495:G:C	W18S	0.686
5:143820504:A:G	E21G	0.681
5:143820537:G:C	R32T	0.679
5:143820497:A:G	K19E	0.663
5:143820521:G:C	D27H	0.657

dbSNP variants (sampled 300 via entrez): RS1000000116 (5:143820965 G>C), RS1000074044 (5:143820080 A>G), RS1000292330 (5:143813978 A>G), RS1000541299 (5:143820721 ATG>A,ATGTG), RS1000980595 (5:143818982 C>T), RS1001076956 (5:143818761 C>A), RS1001349125 (5:143814806 T>C), RS1001629061 (5:143819782 A>C,G), RS1001802178 (5:143813729 G>A), RS1001836642 (5:143819864 A>T), RS1001934297 (5:143819996 G>A,C), RS1002533711 (5:143818627 G>C), RS1002803785 (5:143812562 G>C), RS1003036810 (5:143818338 G>T), RS1003679547 (5:143811421 G>A)

Disease associations

OMIM: gene MIM:609961 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003542_121	Night sleep phenotypes	6.000000e-06
GCST006496_3	Glomerular filtration rate change in heart transplantation	2.000000e-06
GCST008830_16	Neurofibrillary tangles	8.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006829	GFR change measurement
EFO:0007043	response to transplant
EFO:0006797	neurofibrillary tangles measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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