TBCCD1

Summary

TBCCD1 (TBCC domain containing 1, HGNC:25546) is a protein-coding gene on chromosome 3q27.3, encoding TBCC domain-containing protein 1 (Q9NVR7). Plays a role in the regulation of centrosome and Golgi apparatus positioning, with consequences on cell shape and cell migration.

Involved in several processes, including maintenance of Golgi location; maintenance of centrosome location; and regulation of cell shape. Located in spindle pole centrosome.

Source: NCBI Gene 55171 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_018138

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25546
Approved symbol	TBCCD1
Name	TBCC domain containing 1
Location	3q27.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10560
Ensembl gene	ENSG00000113838
Ensembl biotype	protein_coding
OMIM	619848
Entrez	55171

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000338733, ENST00000413695, ENST00000424280, ENST00000430560, ENST00000446782, ENST00000479590, ENST00000894070, ENST00000894071, ENST00000894072, ENST00000933583, ENST00000933584, ENST00000971226, ENST00000971227, ENST00000971228

RefSeq mRNA: 3 — MANE Select: NM_018138 NM_001134415, NM_001286749, NM_018138

CCDS: CCDS3276, CCDS75061

Canonical transcript exons

ENST00000338733 — 8 exons

Exon	Start	End
ENSE00001029320	186554254	186554751
ENSE00001029325	186551129	186551279
ENSE00001029326	186554898	186555084
ENSE00001079634	186556409	186556775
ENSE00001079636	186558417	186558572
ENSE00001326385	186567267	186567339
ENSE00001371729	186563994	186564372
ENSE00001823903	186546067	186546955

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 86.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.6969 / max 65.2490, expressed in 1723 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45974	4.4801	1672
45975	2.0989	809
45973	0.1179	43

Top tissues by expression

134 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	86.94	gold quality
endometrium	UBERON:0001295	84.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.63	gold quality
testis	UBERON:0000473	82.49	gold quality
ganglionic eminence	UBERON:0004023	82.45	gold quality
right testis	UBERON:0004534	82.14	gold quality
cortical plate	UBERON:0005343	81.84	gold quality
lymph node	UBERON:0000029	81.78	gold quality
body of pancreas	UBERON:0001150	81.61	gold quality
rectum	UBERON:0001052	81.57	gold quality
ventricular zone	UBERON:0003053	81.46	gold quality
left testis	UBERON:0004533	81.46	gold quality
bone marrow cell	CL:0002092	81.40	gold quality
adrenal tissue	UBERON:0018303	81.35	gold quality
stromal cell of endometrium	CL:0002255	81.31	gold quality
islet of Langerhans	UBERON:0000006	81.19	gold quality
pancreas	UBERON:0001264	81.12	gold quality
smooth muscle tissue	UBERON:0001135	80.74	gold quality
vermiform appendix	UBERON:0001154	80.53	gold quality
bone marrow	UBERON:0002371	80.20	gold quality
tonsil	UBERON:0002372	79.88	gold quality
gall bladder	UBERON:0002110	79.73	gold quality
duodenum	UBERON:0002114	79.64	gold quality
calcaneal tendon	UBERON:0003701	79.48	gold quality
descending thoracic aorta	UBERON:0002345	79.17	gold quality
mucosa of stomach	UBERON:0001199	79.16	gold quality
leukocyte	CL:0000738	79.02	gold quality
monocyte	CL:0000576	78.89	gold quality
placenta	UBERON:0001987	78.76	gold quality
right lobe of thyroid gland	UBERON:0001119	78.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting TBCCD1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-618	97.62	67.46	861
HSA-MIR-6831-3P	97.49	69.29	505
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-517-5P	97.13	68.43	781

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbccd1	ENSDARG00000056886
mus_musculus	Tbccd1	ENSMUSG00000004462
rattus_norvegicus	Tbccd1	ENSRNOG00000026458
caenorhabditis_elegans	C54G6.2	WBGENE00016931

Protein

Protein identifiers

TBCC domain-containing protein 1 — Q9NVR7 (reviewed: Q9NVR7)

All UniProt accessions (3): Q9NVR7, C9J4M0, C9JUE9

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of centrosome and Golgi apparatus positioning, with consequences on cell shape and cell migration.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole.

Similarity. Belongs to the TBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NVR7-1	1	yes
Q9NVR7-2	2

RefSeq proteins (3): NP_001127887, NP_001273678, NP_060608* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006599	CARP_motif	Domain
IPR012945	Tubulin-bd_cofactor_C_dom	Domain
IPR016098	CAP/MinC_C	Homologous_superfamily
IPR017901	C-CAP_CF_C-like	Domain
IPR036223	CAP_C_sf	Homologous_superfamily
IPR039589	TBCC1	Family

Pfam: PF07986

UniProt features (8 total): sequence conflict 3, splice variant 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NVR7-F1	86.97	0.70

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 92 (showing top): GOBP_REGULATION_OF_CELL_MORPHOGENESIS, TGCGCANK_UNKNOWN, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_MAINTENANCE_OF_LOCATION, GOCC_CENTROSOME, GOBP_GOLGI_LOCALIZATION, GOBP_ORGANELLE_LOCALIZATION, GOCC_SPINDLE, GOBP_REGULATION_OF_CELL_SHAPE, ZHENG_BOUND_BY_FOXP3, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GREGORY_SYNTHETIC_LETHAL_WITH_IMATINIB, GOBP_MAINTENANCE_OF_ORGANELLE_LOCATION, GOBP_MICROTUBULE_ORGANIZING_CENTER_LOCALIZATION, GOCC_SPINDLE_POLE_CENTROSOME

GO Biological Process (4): regulation of cell shape (GO:0008360), regulation of cell migration (GO:0030334), maintenance of centrosome location (GO:0051661), maintenance of Golgi location (GO:0051684)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): spindle pole centrosome (GO:0031616), spindle pole (GO:0000922), cytoplasm (GO:0005737), centrosome (GO:0005813), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
maintenance of organelle location	2
cellular anatomical structure	2
regulation of cell morphogenesis	1
regulation of biological quality	1
cell migration	1
regulation of cell motility	1
centrosome localization	1
Golgi localization	1
binding	1
spindle pole	1
centrosome	1
spindle	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBCCD1	MORN1	Q5T089	580
TBCCD1	GFOD2	Q3B7J2	568
TBCCD1	CETN2	P41208	536
TBCCD1	ANO8	Q9HCE9	499
TBCCD1	FAM222A	Q5U5X8	478
TBCCD1	POPDC1	Q8NE79	476
TBCCD1	TLK2	Q86UE8	476
TBCCD1	CEP76	Q8TAP6	475
TBCCD1	BCKDHB	P21953	474
TBCCD1	GINS1	Q14691	463
TBCCD1	ICMT	O60725	458
TBCCD1	ANKRD13D	Q6ZTN6	458
TBCCD1	CRTAM	O95727	456
TBCCD1	CCT7	Q99832	454
TBCCD1	SPATC1	Q76KD6	450

IntAct

29 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
PPP2CB	CEP43	psi-mi:“MI:0914”(association)	0.730
PPP2R1A	PPFIA3	psi-mi:“MI:0914”(association)	0.670
LURAP1L	TBCCD1	psi-mi:“MI:0915”(physical association)	0.560
KRBA1	TRIM27	psi-mi:“MI:0914”(association)	0.530
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
Ppp2r1a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
PPP2R1A	INTS2	psi-mi:“MI:0914”(association)	0.350
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350
TBCCD1	FAM13A	psi-mi:“MI:0914”(association)	0.350
KRBA1	TOMM40	psi-mi:“MI:0914”(association)	0.350
PPP2CA	SUPT5H	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
TFPT	KRBA1	psi-mi:“MI:0914”(association)	0.350
CCDC9	USP9Y	psi-mi:“MI:0914”(association)	0.350
RNF10	CTSV	psi-mi:“MI:0914”(association)	0.350
TBCCD1	PPP2R1B	psi-mi:“MI:0914”(association)	0.350
TBCCD1	IFT88	psi-mi:“MI:0403”(colocalization)	0.270
IFT88	TBCCD1	psi-mi:“MI:0403”(colocalization)	0.270
TBCCD1	CETN1	psi-mi:“MI:0403”(colocalization)	0.270
TBCCD1	LURAP1L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (75): TBCCD1 (Affinity Capture-RNA), TBCCD1 (Affinity Capture-RNA), TBCCD1 (Affinity Capture-MS), TBCCD1 (Affinity Capture-MS), TBCCD1 (Affinity Capture-MS), TBCCD1 (Affinity Capture-MS), PPP2R3B (Affinity Capture-MS), TBCCD1 (Affinity Capture-MS), USP47 (Affinity Capture-MS), TBCCD1 (Affinity Capture-MS), FAM13A (Affinity Capture-MS), PPP2CA (Affinity Capture-MS), PPP2R1B (Affinity Capture-MS), HIC2 (Affinity Capture-MS), PPP2R1A (Affinity Capture-MS)

ESM2 similar proteins: A0A571BF63, A1L0Z4, A1ZAG4, A4IF93, A4QP31, A5HEI1, D3IUT5, F4JS25, F4KCC2, F6S215, O00443, O65418, Q08AV6, Q0JF48, Q4R6I5, Q5FVR8, Q5Q0E6, Q5RAY1, Q5RD58, Q5TEA3, Q5ZKT1, Q61194, Q61QK6, Q640P7, Q69KN0, Q6DRD4, Q7TT23, Q7XZU2, Q8BMQ2, Q8C6S9, Q8GYU3, Q8H1U4, Q8L6Y4, Q8LLD0, Q8N957, Q8NB91, Q8NHS4, Q8RWM3, Q96N23, Q9FFF9

Diamond homologs: A1L0Z4, A4IF93, A4QP31, Q08AV6, Q5FVR8, Q5ZKT1, Q640P7, Q9NVR7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	28.5×	5e-06
Mitotic Prometaphase	5	20.4×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2044 predictions. Top by Δscore:

Variant	Effect	Δscore
3:186558571:AGC:A	acceptor_loss	1.0000
3:186558572:GCT:G	acceptor_loss	1.0000
3:186558573:C:CC	acceptor_gain	1.0000
3:186558573:C:T	acceptor_loss	1.0000
3:186558574:T:G	acceptor_loss	1.0000
3:186558578:C:CT	acceptor_gain	1.0000
3:186558578:C:T	acceptor_gain	1.0000
3:186558579:A:T	acceptor_gain	1.0000
3:186554378:C:CT	acceptor_gain	0.9900
3:186556500:CAGTT:C	acceptor_gain	0.9900
3:186556501:A:T	acceptor_gain	0.9900
3:186556775:TCTAA:T	acceptor_loss	0.9900
3:186556776:C:CA	acceptor_loss	0.9900
3:186556776:C:CC	acceptor_gain	0.9900
3:186558411:GAGTA:G	donor_loss	0.9900
3:186558412:AGTAC:A	donor_loss	0.9900
3:186558413:GTACC:G	donor_loss	0.9900
3:186558414:TACCT:T	donor_loss	0.9900
3:186558415:A:AG	donor_loss	0.9900
3:186558568:GAAAG:G	acceptor_gain	0.9900
3:186558570:AAG:A	acceptor_gain	0.9900
3:186558571:AG:A	acceptor_gain	0.9900
3:186563988:CCGTA:C	donor_loss	0.9900
3:186563989:CGTA:C	donor_loss	0.9900
3:186563990:GTACC:G	donor_loss	0.9900
3:186563991:TACCT:T	donor_loss	0.9900
3:186563992:A:C	donor_loss	0.9900
3:186563993:CCT:C	donor_loss	0.9900
3:186564016:T:TA	donor_gain	0.9900
3:186546391:CCT:C	donor_gain	0.9800

AlphaMissense

3663 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:186551237:A:C	F529L	0.993
3:186551237:A:T	F529L	0.993
3:186551239:A:G	F529L	0.993
3:186554708:C:G	G364R	0.993
3:186554917:A:C	Y343D	0.993
3:186564148:G:T	A61D	0.993
3:186554707:C:T	G364D	0.992
3:186554721:G:C	S359R	0.992
3:186554721:G:T	S359R	0.992
3:186554723:T:G	S359R	0.992
3:186554732:A:G	C356R	0.992
3:186554913:A:G	L344P	0.992
3:186558482:A:G	W143R	0.992
3:186558482:A:T	W143R	0.992
3:186554474:A:G	W442R	0.991
3:186554474:A:T	W442R	0.991
3:186554935:A:G	C337R	0.991
3:186556421:A:G	W283R	0.991
3:186556421:A:T	W283R	0.991
3:186564161:A:G	W57R	0.991
3:186564161:A:T	W57R	0.991
3:186551226:A:G	L533S	0.990
3:186554919:A:T	I342K	0.990
3:186554982:G:T	A321D	0.989
3:186558550:A:G	F120S	0.989
3:186551230:A:G	W532R	0.987
3:186551230:A:T	W532R	0.987
3:186554288:A:G	W504R	0.987
3:186554288:A:T	W504R	0.987
3:186554730:G:C	C356W	0.987

dbSNP variants (sampled 300 via entrez): RS1000067910 (3:186571568 G>C), RS1000073416 (3:186549349 T>C), RS1000291949 (3:186546759 A>G), RS1000407555 (3:186546645 C>T), RS1000576238 (3:186558969 T>C,G), RS1000599547 (3:186561055 T>C), RS1000619886 (3:186555237 T>C), RS1000629979 (3:186552257 T>C), RS1000690806 (3:186558750 T>C), RS1000919533 (3:186552553 T>C), RS1000958266 (3:186564840 G>A), RS1001020322 (3:186567480 T>A,G), RS1001614252 (3:186546185 T>C), RS1001690576 (3:186564893 A>G), RS1002062422 (3:186570170 G>A,T)

Disease associations

OMIM: gene MIM:619848 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Moderate	Autosomal recessive

Mondo (1): (MONDO:0018393)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005407_2	Glaucoma (primary open-angle)	3.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
triphenyl phosphate	affects expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	increases expression	1
Progesterone	increases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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