BOLL

Summary

BOLL (boule RNA binding protein, HGNC:14273) is a protein-coding gene on chromosome 2q33.1, encoding Protein boule-like (Q8N9W6). Probable RNA-binding protein, which may be required during spermatogenesis.

This gene belongs to the DAZ gene family required for germ cell development. It encodes an RNA-binding protein which is more similar to Drosophila Boule than to human proteins encoded by genes DAZ (deleted in azoospermia) or DAZL (deleted in azoospermia-like). Loss of this gene function results in the absence of sperm in semen (azoospermia). Histological studies demonstrated that the primary defect is at the meiotic G2/M transition. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 66037 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 46 total
• GTEx eGene: eQTL in 1 tissue, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.31 (intermediate), LOEUF 0.81 (unconstrained)
• MANE Select transcript: NM_033030

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14273
Approved symbol	BOLL
Name	boule RNA binding protein
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	BOULE
Ensembl gene	ENSG00000152430
Ensembl biotype	protein_coding
OMIM	606165
Entrez	66037

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000392296

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 4: 1, TSL 5: 1

ENST00000392296, ENST00000321801, ENST00000430004, ENST00000433157, ENST00000434976, ENST00000468827, ENST00000486206, ENST00000696103

RefSeq mRNA: 5 — MANE Select: NM_033030 NM_001284358, NM_001284361, NM_001284362, NM_033030, NM_197970

CCDS: CCDS2324, CCDS2325

Canonical transcript exons

ENST00000392296 — 11 exons

Exon	Start	End
ENSE00002283182	197777059	197777113
ENSE00002316144	197775665	197775740
ENSE00003473014	197756428	197756556
ENSE00003505764	197781722	197781865
ENSE00003514990	197771855	197771982
ENSE00003539782	197778975	197779066
ENSE00003547716	197766532	197766603
ENSE00003578526	197743061	197743159
ENSE00003666160	197757353	197757400
ENSE00003902208	197726890	197728578
ENSE00003966008	197785056	197785319

Expression profiles

Bgee: expression breadth broad, 75 present calls, max score 94.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2853 / max 284.6346, expressed in 4 samples.

Highest expression (Bgee): testis, adult organism, sperm, buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BOLL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	5.8e-40	-1.25	2:197755935:A:C
Muscle Skeletal	eqtl	1.7e-02	+0.10	2:198042419:C:T

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
33100	0.0864	3
33102	0.0626	3
33098	0.0525	3
33097	0.0505	3
33099	0.0233	3
33101	0.0071	4
33103	0.0029	2

Top tissues by expression

showing 100 of 201 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.82	gold quality
adult organism	UBERON:0007023	94.70	gold quality
right testis	UBERON:0004534	94.57	gold quality
sperm	CL:0000019	93.91	gold quality
testis	UBERON:0000473	92.00	gold quality
buccal mucosa cell	CL:0002336	90.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.14	gold quality
tibialis anterior	UBERON:0001385	77.96	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.99	gold quality
gastrocnemius	UBERON:0001388	71.22	gold quality
muscle of leg	UBERON:0001383	71.00	gold quality
ileal mucosa	UBERON:0000331	67.76	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	67.18	gold quality
skeletal muscle tissue	UBERON:0001134	66.45	gold quality
deltoid	UBERON:0001476	65.25	silver quality
muscle tissue	UBERON:0002385	62.21	gold quality
upper leg skin	UBERON:0004262	58.71	gold quality
pancreatic ductal cell	CL:0002079	58.70	silver quality
vastus lateralis	UBERON:0001379	58.27	gold quality
epithelial cell of pancreas	CL:0000083	54.49	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
cerebellar vermis	UBERON:0004720	51.65	gold quality
myocardium	UBERON:0002349	50.25	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
jejunum	UBERON:0002115	44.69	gold quality
thymus	UBERON:0002370	44.64	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
sural nerve	UBERON:0015488	43.11	gold quality
middle temporal gyrus	UBERON:0002771	42.60	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
bone marrow cell	CL:0002092	41.19	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
cartilage tissue	UBERON:0002418	40.77	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
metanephros	UBERON:0000081	40.66	silver quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
bone marrow	UBERON:0002371	40.48	silver quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
medial globus pallidus	UBERON:0002477	40.22	gold quality
epithelium of mammary gland	UBERON:0003244	40.14	gold quality
globus pallidus	UBERON:0001875	39.99	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
oocyte	CL:0000023	39.80	gold quality
urethra	UBERON:0000057	39.80	gold quality
heart right ventricle	UBERON:0002080	39.79	gold quality
pericardium	UBERON:0002407	39.77	gold quality
endothelial cell	CL:0000115	39.75	gold quality
synovial joint	UBERON:0002217	39.70	gold quality
dorsal root ganglion	UBERON:0000044	39.68	gold quality
nipple	UBERON:0002030	39.68	gold quality
bronchial epithelial cell	CL:0002328	39.65	gold quality
decidua	UBERON:0002450	39.65	gold quality
penis	UBERON:0000989	39.64	gold quality
gingiva	UBERON:0001828	39.64	gold quality
bronchus	UBERON:0002185	39.64	gold quality
trigeminal ganglion	UBERON:0001675	39.63	gold quality
tendon of biceps brachii	UBERON:0008188	39.60	gold quality
inferior vagus X ganglion	UBERON:0005363	39.57	gold quality
colonic mucosa	UBERON:0000317	39.56	gold quality
superior surface of tongue	UBERON:0007371	39.56	gold quality
pylorus	UBERON:0001166	39.55	gold quality
renal medulla	UBERON:0000362	39.53	gold quality
skin of hip	UBERON:0001554	39.52	silver quality
pons	UBERON:0000988	39.51	gold quality
medulla oblongata	UBERON:0001896	39.48	gold quality
superior vestibular nucleus	UBERON:0007227	39.47	gold quality
cardia of stomach	UBERON:0001162	39.46	gold quality
mammalian vulva	UBERON:0000997	39.45	gold quality
parietal pleura	UBERON:0002400	39.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	39.40	gold quality
dorsal plus ventral thalamus	UBERON:0001897	39.38	gold quality
tongue	UBERON:0001723	39.37	gold quality
oral cavity	UBERON:0000167	39.35	gold quality
subthalamic nucleus	UBERON:0001906	39.35	gold quality
ventral tegmental area	UBERON:0002691	39.35	gold quality
trachea	UBERON:0003126	39.33	gold quality
parietal lobe	UBERON:0001872	39.32	gold quality
vena cava	UBERON:0004087	39.31	gold quality
pharyngeal mucosa	UBERON:0000355	39.27	gold quality
substantia nigra pars compacta	UBERON:0001965	39.23	gold quality
visceral pleura	UBERON:0002401	39.23	gold quality
postcentral gyrus	UBERON:0002581	39.23	gold quality
body of tongue	UBERON:0011876	39.22	gold quality
trabecular bone tissue	UBERON:0002483	39.18	gold quality
substantia nigra pars reticulata	UBERON:0001966	39.11	gold quality
entorhinal cortex	UBERON:0002728	39.05	gold quality
lateral nuclear group of thalamus	UBERON:0002736	39.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.71

HPA expression

RNA tissue specificity: Tissue enriched

36 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	45.7	high
Olfactory bulb	tissue	4.7
Cerebellum	tissue	4.1	not detected
Corpus callosum	tissue	4.1
Amygdala	tissue	3.6
Skeletal muscle	tissue	3.5	not detected
Cerebral cortex	tissue	3.4	not detected
Retrosplenial cortex	tissue	3.4
Insular cortex	tissue	3.4
Ventral forebrain	tissue	3.2
Basal ganglia	tissue	3.1	not detected
Hippocampal formation	tissue	3.1
Retrosplenial and cingulate cortex	tissue	3.1
Entorhinal cortex	tissue	3.0
Temporal cortex	tissue	3.0
Occipital cortex	tissue	3.0
Prefrontal cortex	tissue	2.8
Putamen	tissue	2.8
Periaqueductal gray	tissue	2.8
Septum	tissue	2.8
Spinal cord	tissue	2.7
Motor cortex	tissue	2.6
Hypothalamus	tissue	2.6
Substantia nigra	tissue	2.6
Medulla oblongata	tissue	2.5
Somatosensory cortex	tissue	2.4
Midbrain	tissue	2.3
Thalamus	tissue	2.1
Superior colliculi	tissue	2.1
Pons	tissue	1.9
Tongue	tissue	1.2
Postcentral gyrus	tissue	0.7
Hippocampus	tissue	0.6	not detected
Nucleus accumbens	tissue	0.4
Locus coeruleus	tissue	0.4
Choroid plexus	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — White matter (4.1), Ventral hippocampus (3.1), Subiculum (2.9), Dorsal hippocampus (2.8), Ventral spinal cord (2.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting BOLL by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 114 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3671	99.90	73.04	3897

Functional genomics

gnomAD constraint: pLI 0.314, LOEUF 0.81, missense Z 0.717 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000392296 — one region, missense o/e 0.85.

Literature-anchored findings (GeneRIF, showing 16)

• BOULE may encode a key conserved switch that regulates progression of germ cells through meiosis in men. (PMID:12499397)
• Role in spermatogenesis. Decreased DAZ proteins in spermatogenic failure may be due to germ cell loss. Transcription of BOULE, DAZL, and DAZ not altered in degrees of spermatogenic failure. No increase of DAZL or BOULE found in DAZ deletion. (PMID:15066460)
• Major group of infertile men with meiotic arrest lack BOULE protein and its putative target, CDC25A expression. Spermatogenic failure may arise from factor(s) upstream of BOULE possibly involved in regulating transcription and/or translation of BOULE. (PMID:15070965)
• BOULE coding sequence mutations are not an important factor in the aetiology of azoospermia. (PMID:15379971)
• mutations in BOULE can be eliminated as a major cause of impaired spermatogenesis. (PMID:15705409)
• Among the three BOULE isoforms, B2 might have the major role for meiotic completion. (PMID:17114206)
• expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population (PMID:19342699)
• CDC25A is subject to translational control by BOLL, which is an evolutionarily conserved mechanism. (PMID:19417033)
• human DAZL (deleted in azoospermia-like) functions in primordial germ-cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes (PMID:19865085)
• Assessing the expression of both CDY1 and BOULE by qualitative RT-PCR is a sensitive and feasible test for predicting the presence of sperm cells in testicular tissue biopsies. (PMID:21474125)
• demonstrate that Boll is also transiently expressed during oogenesis in the fetal mouse ovary, but is simultaneously co-expressed within the same germ cells as Dazl (PMID:24086306)
• Our study demonstrated an oncogenic role of BOLL in CRC despite tumor-specific promoter hypermethylation. (PMID:25605553)
• hypermethylation of DAZL and BOULE promoters in human sperm is associated with human infertility (PMID:27358391)
• Four sterility-related genes, including BOLL, DDX4, HORMAD1, and MAEL, were found to have increased methylation at CpGs of the promoter regions and decreased mRNA expressions in nonobstructive azoospermia and hypospermatogenesis (HS) testis and are believed to be associated with HS. (PMID:28342926)
• Direct reprogramming of human Sertoli cells into male germline stem cells with the self-renewal and differentiation potentials via overexpressing DAZL/DAZ2/BOULE genes. (PMID:34653405)
• Novel Mutations Reduce Expression of Meiotic Regulators SYCE1 and BOLL in Testis of Azoospermic Men from West Bengal, India. (PMID:37957469)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Boll	ENSMUSG00000025977
rattus_norvegicus	Boll	ENSRNOG00000054379
drosophila_melanogaster	bol	FBGN0011206

Paralogs (5): DAZL (ENSG00000092345), DAZ3 (ENSG00000187191), DAZ1 (ENSG00000188120), DAZ4 (ENSG00000205916), DAZ2 (ENSG00000205944)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1922638) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
small testis	1
arrest of spermatogenesis	1
abnormal spermatogenesis	1
male infertility	1
abnormal spermiogenesis	1
decreased testis weight	1
azoospermia	1
arrest of spermiogenesis	1
abnormal male germ cell apoptosis	1
multinucleated giant male germ cells	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R8Y8	100.0%	Diamond
Gallus gallus	Q7T2T1	99.8%	Diamond
Xenopus laevis	O57437	99.3%	Diamond
Macaca fascicularis	Q8WP23	98.9%	Diamond
Xenopus tropicalis	A4IIM2	96.8%	Diamond
Callithrix jacchus	Q9BGN8	94.9%	Diamond
Bos taurus	Q32LC7	93.8%	Diamond
Danio rerio	Q6P0B1	92.6%	Diamond
Oryza sativa Japonica Group	Q6Z358	90.9%	Diamond
Arabidopsis thaliana	P92964	75.4%	Diamond
Schizosaccharomyces pombe 972h-	O42847	57.6%	Diamond
Caenorhabditis elegans	Q20870	49.1%	Diamond
Saccharomyces cerevisiae S288C	P53927	46.5%	Diamond
Ophiostoma ulmi	Q01491	38.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC01923	ncRNA	101927619
PLCL1	protein-coding	5334
MARS2	protein-coding	92935
HSPE1-MOB4	protein-coding	100529241
RFTN2	protein-coding	130132
MOB4	protein-coding	25843
HSPE1	protein-coding	3336

Protein

Protein identifiers

Protein boule-like — Q8N9W6 (reviewed: Q8N9W6)

All UniProt accessions (4): Q8N9W6, A0A8Q3WL03, F2Z2G3, F8WD91

UniProt curated annotations — full annotation on UniProt →

Function. Probable RNA-binding protein, which may be required during spermatogenesis. May act by binding to the 3’-UTR of mRNAs and regulating their translation.

Subunit / interactions. Interacts with DAZ1 and DAZL.

Subcellular location. Cytoplasm.

Tissue specificity. Testis specific. Not expressed in early embryos, primordial germ cells and spermatogonial cells. First expressed in the cytoplasm of spermatocytes and then persists through meiosis.

Similarity. Belongs to the RRM DAZ family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8N9W6-1	1, BOULE2	yes
Q8N9W6-2	2
Q8N9W6-3	3, BOULE1
Q8N9W6-4	4, BOULE3
Q8N9W6-5	5

RefSeq proteins (5): NP_001271287, NP_001271290, NP_001271291, NP_149019, NP_932074 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR043628	DAZ_dom	Domain

Pfam: PF00076

UniProt features (11 total): splice variant 6, domain 2, chain 1, sequence conflict 1, region of interest 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N9W6-F1	64.18	0.25

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): annulus; end piece; mid piece; principal piece

Antibody reliability (HPA): IH enhanced · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 118 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, ATACCTC_MIR202, GOBP_3_UTR_MEDIATED_MRNA_STABILIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TRANSLATIONAL_INITIATION, GOBP_MALE_GAMETE_GENERATION, GOBP_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_TRANSLATIONAL_INITIATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, BROWN_MYELOID_CELL_DEVELOPMENT_UP, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, WEBER_METHYLATED_HCP_IN_SPERM_UP, WEBER_METHYLATED_HCP_IN_FIBROBLAST_DN

GO Biological Process (6): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), positive regulation of translational initiation (GO:0045948), meiotic cell cycle (GO:0051321), 3’-UTR-mediated mRNA stabilization (GO:0070935), regulation of translation (GO:0006417)

GO Molecular Function (6): mRNA 3’-UTR binding (GO:0003730), translation activator activity (GO:0008494), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

21 GO namespaces:

Category	Terms
positive regulation of translation	2
binding	2
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
translational initiation	1
regulation of translational initiation	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
mRNA stabilization	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
mRNA binding	1
translation regulator activity	1
protein binding	1
nucleic acid binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
meiotic cell cycle	BP	direct assay
positive regulation of translational initiation	BP	direct assay
cytoplasm	CC	direct assay
identical protein binding	MF	physical interaction
translation activator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 954 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BOLL	DAZAP2	Q15038	797
BOLL	CDC25A	P30304	745
BOLL	DDX4	Q9NQI0	733
BOLL	SYCP3	Q8IZU3	710
BOLL	ACR	P10323	656
BOLL	CDC25B	P30305	531
BOLL	TEKT1	Q969V4	531
BOLL	STRA8	Q7Z7C7	501
BOLL	DRC11L	A6NCM1	491
BOLL	GDF9	O60383	486
BOLL	NANOS3	P60323	484
BOLL	SPATA22	Q8NHS9	476
BOLL	CNOT7	Q9UIV1	457
BOLL	BMP15	O95972	456
BOLL	ASZ1	Q8WWH4	453

IntAct

Human interaction partners of BOLL in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
ZNF385C	physical association	0.680	4
HNRNPLL	physical association	0.670	4
RBFOX2	physical association	0.670	4
TFG	physical association	0.610	4
C1orf94	physical association	0.560	3
NPBWR2	physical association	0.560	3
RBPMS	physical association	0.560	3
DAZ1	physical association	0.550	2
PUM2	physical association	0.510	3
DAZL	physical association	0.370	1
SERF2	physical association	0.370	1
ACY1	association	0.350	1

BioGRID (53 interactions; top human partners by supporting records): ACY1 (Affinity Capture-MS; 3 records), CDC20B (Affinity Capture-MS; 3 records), UBA5 (Affinity Capture-MS; 3 records), C1orf94 (Two-hybrid; 2 records), RBFOX2 (Two-hybrid; 2 records), TFG (Two-hybrid; 2 records), ZNF385C (Two-hybrid; 2 records), AGRN (Two-hybrid), ARID5A (Two-hybrid), ATXN2L (Two-hybrid), C4orf45 (Two-hybrid), CBX2 (Two-hybrid), DAZ1 (Two-hybrid), DCANP1 (Two-hybrid), EHHADH (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for BOLL: 46 ClinVar records (0 pathogenic / likely pathogenic); 21 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 1,314):

Position(s)	Effect	Δscore	Sites
2:197743059–197743060	donor_loss	1.0000	4
2:197743160–197743161	acceptor_loss	1.0000	6
2:197743163	acceptor_gain	1.0000
2:197756426–197756427	donor_loss	1.0000	4
2:197743059–197743060	donor_loss	0.9900	2
2:197743167	acceptor_gain	0.9900
2:197757351–197757352	donor_loss	0.9900	5
2:197769508	acceptor_gain	0.9900
2:197771850	donor_loss	0.9900	3
2:197771853–197771854	donor_loss	0.9900	6

AlphaMissense

523 missense substitutions predicted likely pathogenic (of 1,822 scored), across 115 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F77	8	0.997	1.000
F36	8	0.994	1.000
F53	8	0.993	0.999
D67	8	0.991	0.998
F80	8	0.971	1.000
F147	8	0.931	0.996
D41	8	0.898	0.975
N104	8	0.846	0.984
F52	7	0.910	0.995
I40	7	0.815	0.998
K73	6	1.000	1.000
G74	6	0.998	1.000
G57	6	0.994	1.000
K111	6	0.993	0.999
R34	6	0.991	1.000
A108	6	0.989	1.000
K63	6	0.986	0.998
K101	6	0.983	0.997
V59	6	0.978	0.999
G76	6	0.969	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:606165 | disease phenotypes:

GWAS associations

21 associations:

Study	Trait	p-value
GCST010701_19	Cortical surface area (MOSTest)	2e-37
GCST007565_181	Morning person	1e-27
GCST006803_15	Schizophrenia	4e-13
GCST010702_115	Subcortical volume (MOSTest)	1e-11
GCST010703_247	Brain morphology (MOSTest)	1e-11
GCST002539_26	Schizophrenia	2e-11
GCST004521_281	Autism spectrum disorder or schizophrenia	3e-11
GCST007293_132	Body fat distribution (arm fat ratio)	8e-11
GCST010700_25	Cortical thickness (MOSTest)	2e-10
GCST010699_54	Brain morphology (min-P)	1e-9
GCST007294_2	Body fat distribution (trunk fat ratio)	3e-9
GCST004521_50	Autism spectrum disorder or schizophrenia	7e-9
GCST010698_56	Subcortical volume (min-P)	2e-8
GCST010730_2	Rheumatoid arthritis	2e-8
GCST009720_13	Asthma	3e-8
GCST000262_1	Intracranial aneurysm	4e-8
GCST004132_10	Crohn’s disease	7e-8
GCST007293_87	Body fat distribution (arm fat ratio)	2e-7
GCST007293_51	Body fat distribution (arm fat ratio)	1e-6
GCST007294_134	Body fat distribution (trunk fat ratio)	4e-6
GCST005588_16	Idiopathic dilated cardiomyopathy	9e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0004341	body fat distribution
EFO:0008328	chronotype measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
CGP 52608	affects binding, increases reaction	1
(((4-nitrophenyl)amino)(2,2,4,4-tetramethyl thiochroman-6-yl)amino) methane-1-thione	increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
Irinotecan	affects cotreatment, increases response to substance	1
Fulvestrant	affects cotreatment, decreases methylation	1
Amiodarone	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Leucovorin	affects cotreatment, increases response to substance	1
Fluorouracil	affects cotreatment, increases response to substance	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.