FSCB

Summary

FSCB (fibrous sheath CABYR binding protein, HGNC:20494) is a protein-coding gene on chromosome 14q21.2, encoding Fibrous sheath CABYR-binding protein (Q5H9T9). May be involved in the later stages of fibrous sheath biogenesis and spermatozoa capacitation.

Predicted to enable calcium ion binding activity. Predicted to be involved in negative regulation of protein sumoylation. Predicted to be located in motile cilium. Predicted to be active in sperm fibrous sheath and sperm principal piece.

Source: NCBI Gene 84075 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 153 total
• MANE Select transcript: NM_032135

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20494
Approved symbol	FSCB
Name	fibrous sheath CABYR binding protein
Location	14q21.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434F1017
Ensembl gene	ENSG00000189139
Ensembl biotype	protein_coding
OMIM	611779
Entrez	84075

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000340446

RefSeq mRNA: 1 — MANE Select: NM_032135 NM_032135

CCDS: CCDS9679

Canonical transcript exons

ENST00000340446 — 1 exons

Exon	Start	End
ENSE00001367273	44504149	44507283

Expression profiles

Bgee: expression breadth broad, 17 present calls, max score 98.42.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0325 / max 30.4938, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143028	0.0325	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.20	gold quality
left testis	UBERON:0004533	86.12	gold quality
right testis	UBERON:0004534	85.34	gold quality
testis	UBERON:0000473	83.03	gold quality
epithelial cell of pancreas	CL:0000083	62.77	gold quality
lower lobe of lung	UBERON:0008949	61.82	silver quality
secondary oocyte	CL:0000655	60.69	gold quality
pancreatic ductal cell	CL:0002079	56.78	silver quality
tibialis anterior	UBERON:0001385	55.88	silver 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
adult organism	UBERON:0007023	53.78	silver quality
upper arm skin	UBERON:0004263	53.52	gold quality
myocardium	UBERON:0002349	50.25	gold quality
sural nerve	UBERON:0015488	49.91	gold quality
deltoid	UBERON:0001476	49.38	gold quality
quadriceps femoris	UBERON:0001377	48.82	gold quality
vastus lateralis	UBERON:0001379	48.34	gold quality
layer of synovial tissue	UBERON:0007616	48.03	gold quality
buccal mucosa cell	CL:0002336	47.86	gold quality
Brodmann (1909) area 46	UBERON:0006483	47.84	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
cardia of stomach	UBERON:0001162	46.20	gold quality
ileal mucosa	UBERON:0000331	44.98	silver quality
oocyte	CL:0000023	43.82	gold quality
superior surface of tongue	UBERON:0007371	43.44	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
ventral tegmental area	UBERON:0002691	42.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting FSCB, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-1183	98.75	67.10	1116
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-647	97.73	67.79	927
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-4678	97.59	68.31	902
HSA-MIR-125B-2-3P	96.69	68.38	1210
HSA-MIR-4636	91.87	64.93	40

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fscb	ENSMUSG00000043060
rattus_norvegicus	Fscb	ENSRNOG00000086903

Protein

Protein identifiers

Fibrous sheath CABYR-binding protein — Q5H9T9 (reviewed: Q5H9T9)

All UniProt accessions (1): Q5H9T9

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the later stages of fibrous sheath biogenesis and spermatozoa capacitation. Inhibits ROPN1 and ROPN1L SUMOylation. Binds calcium.

Subunit / interactions. Interacts with CABYR. Interacts with ROPN1 and ROPN1L; the interaction increases upon spermatozoa capacitation conditions.

Subcellular location. Cell projection. Cilium. Flagellum.

Post-translational modifications. Phosphorylated by PKA upon spermatozoa capacitation conditions.

RefSeq proteins (1): NP_115511* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043375	FSCB	Family

UniProt features (28 total): sequence variant 9, compositionally biased region 6, sequence conflict 6, region of interest 5, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5H9T9-F1	46.37	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.

Post-translational modifications (1): 160

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 36 (showing top): GOBP_REGULATION_OF_PROTEIN_SUMOYLATION, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_PROTEIN_SUMOYLATION, TGACATY_UNKNOWN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_MODIFICATION_PROCESS, GOCC_MOTILE_CILIUM, GOCC_SPERM_PRINCIPAL_PIECE, GOCC_CILIUM, GOBP_REGULATION_OF_PROTEIN_MODIFICATION_PROCESS, HSF2_01, GOBP_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_SUMOYLATION, GOCC_SPERM_FIBROUS_SHEATH

GO Biological Process (1): negative regulation of protein sumoylation (GO:0033234)

GO Molecular Function (1): calcium ion binding (GO:0005509)

GO Cellular Component (5): sperm fibrous sheath (GO:0035686), sperm principal piece (GO:0097228), 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
sperm flagellum	2
protein sumoylation	1
regulation of protein sumoylation	1
negative regulation of protein modification by small protein conjugation or removal	1
metal ion binding	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FSCB	CABYR	O75952	953
FSCB	LRCOL1	A6NCL2	595
FSCB	ROPN1L	Q96C74	589
FSCB	ROPN1	Q9HAT0	578
FSCB	TMEM190	Q8WZ59	571
FSCB	PRKACA	P17612	554
FSCB	PRKACG	P22612	554
FSCB	PRKACB	P22694	552
FSCB	GAPDHS	O14556	527
FSCB	FAM229B	Q4G0N7	519
FSCB	SPMIP4	Q8N865	514
FSCB	AKAP3	O75969	494
FSCB	AADAC	P22760	461
FSCB	SPA17	Q15506	446
FSCB	CCDC54	Q8NEL0	435

IntAct

0 interactions, top by confidence:

BioGRID (1): FSCB (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUW6, A1EGX6, A4FU49, A6NJ88, A6QP92, E9PAV3, E9Q0C6, F1QU13, O94854, P18583, P24587, P27546, P27816, P36225, P43597, P70670, Q08DY0, Q2T9N0, Q32L62, Q4R729, Q4V7A4, Q5H9T9, Q5M7W5, Q5SWP3, Q5XHX6, Q5XPK0, Q659K0, Q68DN1, Q68FX6, Q69ZZ9, Q6AZ54, Q6P6B1, Q6ZRG5, Q70KF4, Q710D7, Q810T2, Q8K4E0, Q8N3K9, Q8TCU4, Q8WWL7

Diamond homologs: A1EGX6, Q2T9N0, Q4V7A4, Q5H9T9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	131
Likely benign	19
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

13 predictions. Top by Δscore:

Variant	Effect	Δscore
14:44507148:T:A	donor_gain	0.5100
14:44507235:T:TA	donor_gain	0.5100
14:44507237:C:CT	donor_gain	0.3700
14:44507219:C:CT	donor_gain	0.3500
14:44507220:T:TT	donor_gain	0.3500
14:44507149:C:A	donor_gain	0.2900
14:44507238:C:CT	donor_gain	0.2900
14:44507219:CTACA:C	donor_gain	0.2300
14:44504851:AGG:A	donor_gain	0.2200
14:44507234:AT:A	donor_gain	0.2200
14:44504946:T:TA	donor_gain	0.2100
14:44507033:T:A	acceptor_gain	0.2000
14:44507132:CAAG:C	donor_gain	0.2000

AlphaMissense

5286 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:44506811:C:A	W59C	0.902
14:44506811:C:G	W59C	0.902
14:44506824:A:G	L55P	0.895
14:44504546:A:C	F814L	0.861
14:44504546:A:T	F814L	0.861
14:44504548:A:G	F814L	0.861
14:44506511:A:C	F159L	0.852
14:44506511:A:T	F159L	0.852
14:44506513:A:G	F159L	0.852
14:44506394:A:C	F198L	0.843
14:44506394:A:T	F198L	0.843
14:44506396:A:G	F198L	0.843
14:44506813:A:G	W59R	0.840
14:44506813:A:T	W59R	0.840
14:44506568:C:A	W140C	0.833
14:44506568:C:G	W140C	0.833
14:44506570:A:G	W140R	0.815
14:44506570:A:T	W140R	0.815
14:44504801:A:C	F729L	0.813
14:44504801:A:T	F729L	0.813
14:44504803:A:G	F729L	0.813
14:44506802:T:A	R62S	0.796
14:44506802:T:G	R62S	0.796
14:44504636:A:C	F784L	0.791
14:44504636:A:T	F784L	0.791
14:44504638:A:G	F784L	0.791
14:44504708:A:C	F760L	0.758
14:44504708:A:T	F760L	0.758
14:44504710:A:G	F760L	0.758
14:44506334:A:C	F218L	0.756

dbSNP variants (sampled 300 via entrez): RS1000733264 (14:44506540 T>C), RS1001178044 (14:44507092 T>G), RS1002698061 (14:44504187 C>A), RS1003308956 (14:44508749 C>A,G), RS1003372114 (14:44504975 C>T), RS1003667523 (14:44509013 T>A,C), RS1004691243 (14:44504118 T>C), RS1005244548 (14:44509063 A>C,G), RS1005321365 (14:44509007 G>A), RS1005596955 (14:44508716 A>AT), RS1008269467 (14:44505094 C>A,G,T), RS1010915221 (14:44505110 T>C), RS1011273513 (14:44504390 G>C), RS1011288838 (14:44503908 T>C), RS1011886727 (14:44504138 A>G)

Disease associations

OMIM: gene MIM:611779 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	Limited	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_886	Obesity-related traits	9.000000e-06
GCST007401_9	Factor VII activity	1.000000e-06
GCST009391_514	Metabolite levels	9.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005118	IGFBP-1 measurement
EFO:0004619	factor VII measurement
EFO:0010117	pyruvate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome