BBOF1

Summary

BBOF1 (basal body orientation factor 1, HGNC:19855) is a protein-coding gene on chromosome 14q24.3, encoding Basal body-orientation factor 1 (Q8ND07). Plays an essential role in sperm motility and male fertility by stabilizing the sperm flagellar axonemal structure.

Predicted to be involved in sperm axoneme assembly. Predicted to act upstream of or within several processes, including cilium movement involved in cell motility; negative regulation of microtubule depolymerization; and protein stabilization. Predicted to be located in axoneme; ciliary basal body; and sperm flagellum.

Source: NCBI Gene 80127 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 81 total — 3 pathogenic
• MANE Select transcript: NM_025057

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19855
Approved symbol	BBOF1
Name	basal body orientation factor 1
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	FBB10
Ensembl gene	ENSG00000119636
Ensembl biotype	protein_coding
OMIM	620496
Entrez	80127

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000394009, ENST00000463558, ENST00000464394, ENST00000477986, ENST00000489323, ENST00000492026, ENST00000492247, ENST00000901145, ENST00000901146

RefSeq mRNA: 1 — MANE Select: NM_025057 NM_025057

CCDS: CCDS32119

Canonical transcript exons

ENST00000394009 — 12 exons

Exon	Start	End
ENSE00001680457	74022916	74023144
ENSE00001839924	74064688	74066092
ENSE00002317144	74019349	74019534
ENSE00003479126	74055584	74055685
ENSE00003496380	74049702	74050195
ENSE00003549093	74034028	74034171
ENSE00003591215	74040565	74040645
ENSE00003607736	74029184	74029249
ENSE00003612281	74056906	74056980
ENSE00003639873	74046060	74046130
ENSE00003648404	74057144	74057258
ENSE00003785047	74047930	74048074

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 98.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.1740 / max 226.2951, expressed in 1449 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140567	4.9230	1278
140566	2.1862	966
140568	0.0647	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	98.70	gold quality
epithelium of bronchus	UBERON:0002031	98.42	gold quality
bronchus	UBERON:0002185	97.64	gold quality
right uterine tube	UBERON:0001302	94.72	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.60	gold quality
sperm	CL:0000019	93.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.48	gold quality
male germ cell	CL:0000015	92.39	gold quality
nasal cavity epithelium	UBERON:0005384	90.96	gold quality
caput epididymis	UBERON:0004358	90.38	gold quality
epithelium of nasopharynx	UBERON:0001951	89.18	gold quality
left testis	UBERON:0004533	88.72	gold quality
parotid gland	UBERON:0001831	88.62	silver quality
tendon of biceps brachii	UBERON:0008188	88.39	silver quality
right testis	UBERON:0004534	88.16	gold quality
buccal mucosa cell	CL:0002336	88.04	silver quality
testis	UBERON:0000473	87.57	gold quality
calcaneal tendon	UBERON:0003701	87.20	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.94	silver quality
vena cava	UBERON:0004087	85.80	silver quality
tendon	UBERON:0000043	85.53	gold quality
sural nerve	UBERON:0015488	84.83	gold quality
nasal cavity mucosa	UBERON:0001826	84.68	gold quality
nucleus accumbens	UBERON:0001882	84.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.47	gold quality
caudate nucleus	UBERON:0001873	84.36	gold quality
endometrium	UBERON:0001295	83.93	gold quality
hypothalamus	UBERON:0001898	83.78	gold quality
anterior cingulate cortex	UBERON:0009835	83.62	gold quality
cingulate cortex	UBERON:0003027	83.57	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.68
E-CURD-114	yes	10.92
E-GEOD-130148	yes	10.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting BBOF1, 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-548C-3P	99.99	74.01	7587
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-7-5P	99.67	70.53	1809

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bbof1b	ENSDARG00000062924
mus_musculus	Bbof1	ENSMUSG00000057265
rattus_norvegicus	Bbof1	ENSRNOG00000011376

Paralogs (1): CCDC166 (ENSG00000255181)

Protein

Protein identifiers

Basal body-orientation factor 1 — Q8ND07 (reviewed: Q8ND07)

Alternative names: Coiled-coil domain-containing protein 176

All UniProt accessions (3): Q8ND07, A0A0B4J2D7, G3V488

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in sperm motility and male fertility by stabilizing the sperm flagellar axonemal structure. May be required for the stability of ODF2 and MANS1 proteins. Dispensable for the assembly and function of motile cilia.

Subunit / interactions. Interacts with MNS1 and ODF2.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium basal body. Flagellum axoneme.

Similarity. Belongs to the BBOF1 family.

RefSeq proteins (1): NP_079333* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032777	DUF4515	Domain

Pfam: PF14988

UniProt features (9 total): sequence variant 4, coiled-coil region 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8ND07-F1	81.40	0.56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, YANG_BREAST_CANCER_ESR1_LASER_UP, GOBP_MALE_GAMETE_GENERATION, CHANDRAN_METASTASIS_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, AGGCACT_MIR5153P, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, chr14q24, GOBP_MICROTUBULE_DEPOLYMERIZATION, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_PROTEIN_STABILIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY

GO Biological Process (7): negative regulation of microtubule depolymerization (GO:0007026), sperm axoneme assembly (GO:0007288), single fertilization (GO:0007338), flagellated sperm motility (GO:0030317), motile cilium assembly (GO:0044458), protein stabilization (GO:0050821), cilium movement involved in cell motility (GO:0060294)

GO Molecular Function (0):

GO Cellular Component (8): axoneme (GO:0005930), ciliary basal body (GO:0036064), sperm flagellum (GO:0036126), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cilium-dependent cell motility	2
cilium	2
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
developmental process involved in reproduction	1
axoneme assembly	1
sperm flagellum assembly	1
fertilization	1
cilium movement involved in cell motility	1
sperm motility	1
cilium assembly	1
regulation of protein stability	1
cilium movement	1
cell motility	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
microtubule organizing center	1
9+2 motile cilium	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BBOF1	CCDC78	A2IDD5	559
BBOF1	MROH8	Q9H579	499
BBOF1	FBXO36	Q8NEA4	485
BBOF1	C1orf74	Q96LT6	479
BBOF1	IQSEC2	Q5JU85	458
BBOF1	GPR160	Q9UJ42	448
BBOF1	C7orf57	Q8NEG2	434
BBOF1	OR12D3	Q9UGF7	432
BBOF1	KSR2	Q6VAB6	423
BBOF1	RPS6KA6	Q9UK32	380
BBOF1	CEP135	Q66GS9	378
BBOF1	DRC3	Q9H069	370
BBOF1	MOS	P00540	366
BBOF1	CCDC146	Q8IYE0	355
BBOF1	CETN2	P41208	348

IntAct

3 interactions, top by confidence:

A	B	Type	Score
BBOF1	htpG	psi-mi:“MI:0915”(physical association)	0.370
BBOF1		psi-mi:“MI:0915”(physical association)	0.370

BioGRID (7): CCDC176 (Affinity Capture-MS), RPS19 (Cross-Linking-MS (XL-MS)), HSPA1A (Cross-Linking-MS (XL-MS)), CCDC176 (Cross-Linking-MS (XL-MS)), EEA1 (Cross-Linking-MS (XL-MS)), CCDC176 (Two-hybrid), CCDC176 (Affinity Capture-Western)

ESM2 similar proteins: A0AUP1, A0JMY4, A3KQH2, D6REC4, E1C760, F1QRC1, F1RKB1, F7AEX0, Q15051, Q17QH9, Q2IA00, Q32KY1, Q3USS3, Q3V079, Q3ZC62, Q45GW3, Q4R6T7, Q4R7Y8, Q4R8R3, Q4R8Y5, Q4V8E4, Q5PQQ6, Q5XI65, Q5XIR6, Q6P0R8, Q6P5U8, Q7T0Y4, Q7Z4T9, Q80VN0, Q8BP00, Q8BRC6, Q8C6E0, Q8C9J3, Q8CDK3, Q8CDV6, Q8HZY8, Q8NA47, Q8NA54, Q8NCU4, Q8ND07

Diamond homologs: A0JMY4, Q08C53, Q3V079, Q4R7Y8, Q8ND07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	55
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1707441	GRCh37/hg19 14q13.3-32.33(chr14:37671058-106985955)x2	Pathogenic
208070	NM_005589.4(ALDH6A1):c.785C>A (p.Ser262Tyr)	Pathogenic
208073	NM_005589.4(ALDH6A1):c.514T>C (p.Tyr172His)	Pathogenic

SpliceAI

3944 predictions. Top by Δscore:

Variant	Effect	Δscore
14:74019532:G:GT	donor_gain	1.0000
14:74019532:GAA:G	donor_gain	1.0000
14:74019535:G:GG	donor_gain	1.0000
14:74029178:CAACA:C	acceptor_loss	1.0000
14:74029179:AACAG:A	acceptor_loss	1.0000
14:74029180:ACAGA:A	acceptor_loss	1.0000
14:74029181:CA:C	acceptor_loss	1.0000
14:74029182:A:AG	acceptor_gain	1.0000
14:74029183:G:GA	acceptor_gain	1.0000
14:74029247:TTGGT:T	donor_loss	1.0000
14:74029248:TGGTG:T	donor_loss	1.0000
14:74029250:G:GC	donor_loss	1.0000
14:74029250:G:GG	donor_gain	1.0000
14:74029251:T:TC	donor_loss	1.0000
14:74029252:GAG:G	donor_loss	1.0000
14:74034023:TACA:T	acceptor_loss	1.0000
14:74034025:CAG:C	acceptor_loss	1.0000
14:74034026:A:AG	acceptor_gain	1.0000
14:74034026:A:AT	acceptor_loss	1.0000
14:74034027:G:GG	acceptor_gain	1.0000
14:74034027:G:T	acceptor_loss	1.0000
14:74034167:ATGAT:A	donor_gain	1.0000
14:74034168:TGAT:T	donor_gain	1.0000
14:74034169:GAT:G	donor_gain	1.0000
14:74034169:GATG:G	donor_gain	1.0000
14:74034170:AT:A	donor_gain	1.0000
14:74034170:ATGTA:A	donor_loss	1.0000
14:74034171:TGTAA:T	donor_loss	1.0000
14:74034172:G:GG	donor_gain	1.0000
14:74034172:GT:G	donor_loss	1.0000

AlphaMissense

3552 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:74050005:G:C	A366P	0.994
14:74049954:G:C	A349P	0.992
14:74029194:T:C	L99P	0.990
14:74049901:T:C	L331P	0.989
14:74049955:C:A	A349D	0.989
14:74049977:A:C	R356S	0.988
14:74049977:A:T	R356S	0.988
14:74034130:T:C	F152L	0.987
14:74034132:C:A	F152L	0.987
14:74034132:C:G	F152L	0.987
14:74040566:T:C	L166P	0.985
14:74046078:G:C	A199P	0.985
14:74046123:G:C	A214P	0.985
14:74055635:G:C	K446N	0.985
14:74055635:G:T	K446N	0.985
14:74055646:T:C	L450S	0.985
14:74034113:T:C	L146P	0.984
14:74055624:T:A	W443R	0.984
14:74055624:T:C	W443R	0.984
14:74055657:T:C	F454L	0.984
14:74055659:T:A	F454L	0.984
14:74055659:T:G	F454L	0.984
14:74055619:T:C	L441S	0.983
14:74055649:G:C	R451P	0.983
14:74049993:T:C	F362L	0.982
14:74049995:C:A	F362L	0.982
14:74049995:C:G	F362L	0.982
14:74050134:T:C	F409L	0.982
14:74050136:T:A	F409L	0.982
14:74050136:T:G	F409L	0.982

dbSNP variants (sampled 300 via entrez): RS1000010434 (14:74044557 G>A), RS1000086842 (14:74064607 T>C), RS1000104336 (14:74035239 G>T), RS1000183271 (14:74031481 T>C), RS1000191651 (14:74079066 C>T), RS1000220760 (14:74036146 C>T), RS1000222607 (14:74079357 C>T), RS1000281458 (14:74025269 G>C), RS1000288820 (14:74077360 G>A), RS1000311168 (14:74025011 G>A), RS1000338604 (14:74069850 C>T), RS1000388875 (14:74024346 C>T), RS1000402525 (14:74017868 G>A), RS1000431751 (14:74037619 C>T), RS1000506543 (14:74078693 A>G)

Disease associations

OMIM: gene MIM:620496 | disease phenotypes: MIM:614105

GenCC curated gene-disease

Mondo (1): methylmalonate semialdehyde dehydrogenase deficiency (MONDO:0013579)

Orphanet (1): Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency (Orphanet:289307)

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001841_10	Palmitoleic acid (16:1n-7) levels	2.000000e-06
GCST004602_207	Mean corpuscular volume	2.000000e-12
GCST004621_72	Red cell distribution width	5.000000e-44
GCST006804_78	Red cell distribution width	4.000000e-38
GCST010002_156	Refractive error	7.000000e-25
GCST90002396_570	Mean reticulocyte volume	8.000000e-09
GCST90002397_367	Mean spheric corpuscular volume	4.000000e-10
GCST90002403_515	Red blood cell count	9.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566402	Methylmalonate Semialdehyde Dehydrogenase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, increases expression	2
Smoke	increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	increases expression	2
aminomethylphosphonic acid (AMPA)	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
ICG 001	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Aspirin	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Silicon Dioxide	decreases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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