BARHL1

Summary

BARHL1 (BarH like homeobox 1, HGNC:953) is a protein-coding gene on chromosome 9q34.13, encoding BarH-like 1 homeobox protein (Q9BZE3).

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including negative regulation of outer hair cell apoptotic process; nervous system development; and sensory perception of sound. Predicted to be located in chromatin. Predicted to be active in nucleus. Biomarker of Alzheimer’s disease; high grade glioma; and triple-receptor negative breast cancer.

Source: NCBI Gene 56751 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_020064

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:953
Approved symbol	BARHL1
Name	BarH like homeobox 1
Location	9q34.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000125492
Ensembl biotype	protein_coding
OMIM	605211
Entrez	56751

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000263610

RefSeq mRNA: 1 — MANE Select: NM_020064 NM_020064

CCDS: CCDS6950

Canonical transcript exons

ENST00000263610 — 3 exons

Exon	Start	End
ENSE00000732934	132589228	132590252
ENSE00000855969	132582606	132583263
ENSE00000855970	132587329	132587551

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 97.39.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.5114 / max 231.9908, expressed in 112 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99152	1.1610	80
99154	0.5114	71
99155	0.2126	58
99153	0.2119	48
99151	0.1658	50
99148	0.1302	44
99156	0.0425	30
99150	0.0363	19
99149	0.0254	15
99157	0.0142	10

Top tissues by expression

234 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	97.39	silver quality
cerebellar hemisphere	UBERON:0002245	85.73	gold quality
cerebellar cortex	UBERON:0002129	85.70	gold quality
cerebellum	UBERON:0002037	85.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.20	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	75.02	gold quality
tendon of biceps brachii	UBERON:0008188	70.48	gold quality
biceps brachii	UBERON:0001507	68.94	gold quality
vastus lateralis	UBERON:0001379	66.35	gold quality
quadriceps femoris	UBERON:0001377	66.10	gold quality
cerebellar vermis	UBERON:0004720	65.73	silver quality
buccal mucosa cell	CL:0002336	63.78	gold quality
nasal cavity epithelium	UBERON:0005384	63.16	gold quality
myocardium	UBERON:0002349	63.00	gold quality
secondary oocyte	CL:0000655	62.66	gold quality
oral cavity	UBERON:0000167	62.27	gold quality
pons	UBERON:0000988	61.62	gold quality
heart right ventricle	UBERON:0002080	60.78	gold quality
medial globus pallidus	UBERON:0002477	60.34	gold quality
globus pallidus	UBERON:0001875	59.68	gold quality
lateral globus pallidus	UBERON:0002476	57.76	gold quality
saphenous vein	UBERON:0007318	57.67	gold quality
jejunal mucosa	UBERON:0000399	57.49	gold quality
ventral tegmental area	UBERON:0002691	57.43	gold quality
vena cava	UBERON:0004087	57.34	gold quality
Brodmann (1909) area 46	UBERON:0006483	57.05	gold quality
superior vestibular nucleus	UBERON:0007227	56.90	silver quality
substantia nigra pars compacta	UBERON:0001965	56.87	silver quality
substantia nigra pars reticulata	UBERON:0001966	56.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.33

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA0877.2	BARHL1	NK
MA0877.3	BARHL1	NK
MA0877.4	BARHL1	NK

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): ATOH1

miRNA regulators (miRDB)

43 targeting BARHL1, 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-5692A	100.00	74.40	6850
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-4700-5P	98.63	67.43	1915

Literature-anchored findings (GeneRIF, showing 2)

• expression of Barhl1 decelerates tumor growth both in human and in murine medulloblastomas. (PMID:21602885)
• Homeobox Protein BarH-like 1 Promotes Gastric Cancer Progression by Activating Coiled-Coil Domain-Containing Protein 178. (PMID:38358459)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	barhl1b	ENSDARG00000019013
danio_rerio	barhl1a	ENSDARG00000035508
mus_musculus	Barhl1	ENSMUSG00000026805
rattus_norvegicus	Barhl1	ENSRNOG00000013209
drosophila_melanogaster	B-H2	FBGN0004854
drosophila_melanogaster	B-H1	FBGN0011758
caenorhabditis_elegans		WBGENE00000451
caenorhabditis_elegans		WBGENE00000452

Paralogs (3): BARX2 (ENSG00000043039), BARX1 (ENSG00000131668), BARHL2 (ENSG00000143032)

Protein

Protein identifiers

BarH-like 1 homeobox protein — Q9BZE3 (reviewed: Q9BZE3)

All UniProt accessions (1): Q9BZE3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Similarity. Belongs to the BAR homeobox family.

RefSeq proteins (1): NP_064448* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR050848	Homeobox_TF	Family

Pfam: PF00046

UniProt features (10 total): compositionally biased region 5, region of interest 3, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZE3-F1	66.80	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 136 (showing top): GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, YAATNRNNNYNATT_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, CMYB_01, SP3_Q3, GOBP_NEUROGENESIS, LHX3_01, GGGTGGRR_PAX4_03, NKX62_Q2, E2F_Q3, GOBP_MIDBRAIN_DEVELOPMENT, HP1SITEFACTOR_Q6, TGACATY_UNKNOWN, GOBP_NEURON_MIGRATION

GO Biological Process (10): neuron migration (GO:0001764), regulation of transcription by RNA polymerase II (GO:0006357), sensory perception of sound (GO:0007605), midbrain development (GO:0030901), outer hair cell apoptotic process (GO:1905584), negative regulation of outer hair cell apoptotic process (GO:1905586), regulation of DNA-templated transcription (GO:0006355), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron apoptotic process (GO:0051402)

GO Molecular Function (5): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
neuron apoptotic process	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cell migration	1
generation of neurons	1
regulation of DNA-templated transcription	1
sensory perception of mechanical stimulus	1
brain development	1
anatomical structure development	1
negative regulation of neuron apoptotic process	1
outer hair cell apoptotic process	1
regulation of outer hair cell apoptotic process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
positive regulation of DNA-templated transcription	1
apoptotic process	1
transcription cis-regulatory region binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1028 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BARHL1	ATOH1	Q92858	846
BARHL1	LHX9	Q9NQ69	745
BARHL1	LHX5	Q9H2C1	619
BARHL1	POU4F3	Q15319	596
BARHL1	PTF1A	Q7RTS3	559
BARHL1	RPGRIP1L	Q68CZ1	549
BARHL1	POU4F1	Q01851	529
BARHL1	LMX1A	Q8TE12	521
BARHL1	FGF8	P55075	504
BARHL1	CTBP2	P56545	449
BARHL1	GFI1	Q99684	448
BARHL1	LHX1	P48742	445
BARHL1	ZIC1	Q15915	438
BARHL1	PAX2	Q02962	436
BARHL1	ARL13B	Q3SXY8	428

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TLE1	BARHL1	psi-mi:“MI:0915”(physical association)	0.370
TLE2	BARHL1	psi-mi:“MI:0915”(physical association)	0.370
MED7	BARHL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): BARHL1 (Affinity Capture-MS), BARHL1 (Two-hybrid), BARHL1 (Two-hybrid)

ESM2 similar proteins: A0A1W2PQ73, A1YF16, A1YG93, A2RU54, A5PKG8, O02786, O14813, O15353, O35602, O43638, O57601, P13297, P19419, P28360, P35548, P41969, P42580, P43687, P49640, P50223, P50548, P52946, P52950, P63156, P63157, P70459, P78413, Q03358, Q14549, Q2VL78, Q2VL79, Q2VL82, Q2VL83, Q2VL84, Q2VL85, Q2VL86, Q2VL87, Q2VL88, Q5NSW5, Q61575

Diamond homologs: A0JPN1, A1YG85, A5PKG8, A6NJ46, A6NMT0, A7MB54, A9L937, B0VXK3, D2KQB0, E7FDX5, M0R6D8, O08686, O13023, O35762, O42365, O43364, O43711, O55144, O88181, O93366, O93367, O93590, P0C1T1, P10035, P14652, P14837, P20009, P28468, P31245, P31246, P31261, P31314, P42583, P42584, P43120, P43345, P43688, P50219, P52945, P52950

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

687 predictions. Top by Δscore:

Variant	Effect	Δscore
9:132583264:G:C	donor_loss	1.0000
9:132586301:GGGA:G	donor_gain	1.0000
9:132586302:G:GT	donor_gain	1.0000
9:132587327:A:AG	acceptor_gain	1.0000
9:132587328:G:GG	acceptor_gain	1.0000
9:132587549:CAGG:C	donor_loss	1.0000
9:132587550:AGGT:A	donor_loss	1.0000
9:132587551:GGTG:G	donor_loss	1.0000
9:132587552:GTGAG:G	donor_loss	1.0000
9:132587553:T:G	donor_loss	1.0000
9:132589218:C:CA	acceptor_gain	1.0000
9:132583264:G:GG	donor_gain	0.9900
9:132586302:G:T	donor_gain	0.9900
9:132587328:GT:G	acceptor_gain	0.9900
9:132589219:G:A	acceptor_gain	0.9900
9:132589222:CCCCA:C	acceptor_loss	0.9900
9:132589224:CCAGG:C	acceptor_loss	0.9900
9:132589225:CAGGA:C	acceptor_loss	0.9900
9:132589226:A:AC	acceptor_loss	0.9900
9:132589226:A:AG	acceptor_gain	0.9900
9:132589227:G:GA	acceptor_loss	0.9900
9:132589227:G:GG	acceptor_gain	0.9900
9:132589227:GGACT:G	acceptor_gain	0.9900
9:132583248:GACTC:G	donor_gain	0.9800
9:132586302:GGA:G	donor_gain	0.9800
9:132586303:GAG:G	donor_gain	0.9800
9:132586305:G:GG	donor_gain	0.9800
9:132587328:GTGAA:G	acceptor_gain	0.9800
9:132582961:G:GT	donor_gain	0.9700
9:132587527:TC:T	donor_gain	0.9700

AlphaMissense

2089 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:132583083:T:C	F96L	1.000
9:132583084:T:C	F96S	1.000
9:132583084:T:G	F96C	1.000
9:132583085:T:A	F96L	1.000
9:132583085:T:G	F96L	1.000
9:132583090:T:A	I98N	1.000
9:132583090:T:C	I98T	1.000
9:132583090:T:G	I98S	1.000
9:132583096:A:C	D100A	1.000
9:132583096:A:T	D100V	1.000
9:132583099:T:A	I101N	1.000
9:132583099:T:C	I101T	1.000
9:132583099:T:G	I101S	1.000
9:132583102:T:A	L102H	1.000
9:132583102:T:C	L102P	1.000
9:132587397:C:A	R179S	1.000
9:132587400:A:G	K180E	1.000
9:132587402:G:C	K180N	1.000
9:132587402:G:T	K180N	1.000
9:132587406:C:A	R182S	1.000
9:132587406:C:G	R182G	1.000
9:132587406:C:T	R182C	1.000
9:132587407:G:A	R182H	1.000
9:132587407:G:T	R182L	1.000
9:132587413:C:A	A184D	1.000
9:132587415:T:A	F185I	1.000
9:132587415:T:C	F185L	1.000
9:132587415:T:G	F185V	1.000
9:132587416:T:C	F185S	1.000
9:132587416:T:G	F185C	1.000

dbSNP variants (sampled 300 via entrez): RS1000276475 (9:132585376 C>G,T), RS1000307593 (9:132585144 C>T), RS1000349719 (9:132582400 T>C), RS1000371685 (9:132588572 C>A,T), RS1000948764 (9:132583947 A>G,T), RS1001213219 (9:132583022 C>A,T), RS1001336070 (9:132580680 C>T), RS1001576198 (9:132583418 T>A), RS1001808544 (9:132589496 C>A,T), RS1002488408 (9:132581945 G>T), RS1002619791 (9:132584623 A>G), RS1002721558 (9:132590540 C>T), RS1002786323 (9:132584316 G>A), RS1002815322 (9:132590711 C>A,T), RS1003228701 (9:132586054 G>A)

Disease associations

OMIM: gene MIM:605211 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases methylation, decreases reaction, affects cotreatment, increases expression	2
Valproic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
decabromobiphenyl ether	decreases expression	1
terbufos	increases methylation	1
trichostatin A	decreases expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	decreases reaction, affects cotreatment, increases expression	1
tetrabromobisphenol A	decreases expression	1
tetrachlorodian	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Catechin	affects cotreatment, decreases reaction, increases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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