TCP11

Summary

TCP11 (t-complex 11, HGNC:11658) is a protein-coding gene on chromosome 6p21.31, encoding T-complex protein 11 homolog (Q8WWU5). Plays a role in the process of sperm capacitation and acrosome reactions.

Involved in germ cell development. Located in acrosomal vesicle and sperm flagellum.

Source: NCBI Gene 6954 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 83 total
• MANE Select transcript: NM_001370687

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11658
Approved symbol	TCP11
Name	t-complex 11
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0229, FPPR
Ensembl gene	ENSG00000124678
Ensembl biotype	protein_coding
OMIM	186982
Entrez	6954

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 15 protein_coding, 11 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000244645, ENST00000311875, ENST00000373974, ENST00000373979, ENST00000394696, ENST00000412155, ENST00000418521, ENST00000427376, ENST00000444780, ENST00000445851, ENST00000455706, ENST00000469514, ENST00000479418, ENST00000486638, ENST00000492680, ENST00000502480, ENST00000503195, ENST00000503908, ENST00000504758, ENST00000505335, ENST00000505400, ENST00000505911, ENST00000507706, ENST00000509988, ENST00000510465, ENST00000512012, ENST00000514751, ENST00000611141, ENST00000673754

RefSeq mRNA: 17 — MANE Select: NM_001370687 NM_001261817, NM_001261818, NM_001261819, NM_001261820, NM_001261821, NM_001366323, NM_001366324, NM_001366325, NM_001366326, NM_001366327, NM_001366328, NM_001366329, NM_001366330, NM_001366331, NM_001366332, NM_001370687, NM_018679

CCDS: CCDS47413, CCDS4799, CCDS59015, CCDS59016, CCDS59017, CCDS59018

Canonical transcript exons

ENST00000311875 — 10 exons

Exon	Start	End
ENSE00001880679	35141205	35141339
ENSE00003466160	35136107	35136218
ENSE00003485900	35120159	35120340
ENSE00003556114	35119228	35119391
ENSE00003576881	35122117	35122337
ENSE00003592533	35129062	35129182
ENSE00003603274	35118075	35118501
ENSE00003632033	35120909	35121045
ENSE00003679947	35120429	35120646
ENSE00003897376	35140747	35140884

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 99.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9534 / max 812.8551, expressed in 24 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73276	0.6945	21
73272	0.0962	3
73273	0.0573	5
73275	0.0413	3
73269	0.0349	3
73271	0.0062	2
203972	0.0061	4
73274	0.0059	2
203971	0.0043	2
73270	0.0034	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.96	gold quality
male germ cell	CL:0000015	99.20	gold quality
left testis	UBERON:0004533	99.13	gold quality
right testis	UBERON:0004534	99.08	gold quality
adult organism	UBERON:0007023	98.36	gold quality
testis	UBERON:0000473	96.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.76	gold quality
oocyte	CL:0000023	77.25	gold quality
secondary oocyte	CL:0000655	71.72	gold quality
right uterine tube	UBERON:0001302	63.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	62.73	gold quality
cartilage tissue	UBERON:0002418	62.13	gold quality
amniotic fluid	UBERON:0000173	61.90	silver quality
tibialis anterior	UBERON:0001385	60.91	silver quality
bronchial epithelial cell	CL:0002328	59.84	silver quality
pancreatic ductal cell	CL:0002079	56.55	silver quality
decidua	UBERON:0002450	56.55	gold quality
cauda epididymis	UBERON:0004360	55.41	gold quality
epithelium of nasopharynx	UBERON:0001951	55.39	gold quality
right coronary artery	UBERON:0001625	54.42	gold quality
ovary	UBERON:0000992	53.87	gold quality
skin of hip	UBERON:0001554	53.60	silver quality
prefrontal cortex	UBERON:0000451	53.18	gold quality
deltoid	UBERON:0001476	53.14	gold quality
left ovary	UBERON:0002119	53.06	gold quality
ganglionic eminence	UBERON:0004023	52.67	gold quality
fallopian tube	UBERON:0003889	52.53	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
endocervix	UBERON:0000458	52.34	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	32.57
E-ANND-3	yes	3.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF76

miRNA regulators (miRDB)

12 targeting TCP11, 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-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-4776-5P	97.14	66.63	405
HSA-MIR-6856-3P	96.47	66.27	781

Literature-anchored findings (GeneRIF, showing 3)

• Results suggest that TCP11 gene is important in sperm function and fertility. (PMID:11756566)
• These results suggest that TCP11 may be responsible for sperm tail morphology and motility. (PMID:21597245)
• Increased TCP11 gene expression can inhibit the proliferation, migration and promote apoptosis of cervical cancer cells. (PMID:37697257)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tcp11	ENSMUSG00000062859
rattus_norvegicus	Tcp11	ENSRNOG00000000499
drosophila_melanogaster	CG16721	FBGN0029820
caenorhabditis_elegans		WBGENE00010875

Paralogs (4): TCP11L2 (ENSG00000166046), TCP11L1 (ENSG00000176148), TCP11X2 (ENSG00000215029), TCP11X1 (ENSG00000268235)

Protein

Protein identifiers

T-complex protein 11 homolog — Q8WWU5 (reviewed: Q8WWU5)

All UniProt accessions (14): A0A140VK95, A0A6E1WXZ9, D6R8Y5, D6R989, D6R9D8, D6R9R9, D6RAC0, D6RBE4, D6RFY8, D6RGC0, D6RGY5, D6RIW4, Q8WWU5, H0Y8T8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the process of sperm capacitation and acrosome reactions. Probable receptor for the putative fertilization-promoting peptide (FPP) at the sperm membrane that may modulate the activity of the adenylyl cyclase cAMP pathway.

Subunit / interactions. Found in a complex at least composed of MROH2B, PRKACA isoform 2 and TCP11. Interacts with MROH2B. Interacts with PRKACA isoform 2. Isoform 2 and isoform 3 interact with ODF1 (via leucine zipper motif).

Subcellular location. Membrane. Cell projection. Cilium. Flagellum. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. Isoform 2 and isoform 3 are expressed in sperm. Isoform 1 is not detected in sperm (at protein level). Testis-specific. Isoform 1, isoform 2 and isoform 3 are expressed in sperm.

Post-translational modifications. Constitutively phosphorylated on serine, threonine and tyrosine residues within the head and tail regions of noncapacitated spermatozoa. Phosphorylation on tyrosine residues increases upon sperm capacitation within the acrosomal region in a protein kinase A (PKA)-dependent signaling pathway.

Similarity. Belongs to the TCP11 family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q8WWU5-1	1, TCP11b	yes
Q8WWU5-2	2, TCP11a
Q8WWU5-3	3, TCP11c
Q8WWU5-4	4
Q8WWU5-5	5
Q8WWU5-6	6
Q8WWU5-7	7

RefSeq proteins (17): NP_001248746, NP_001248747, NP_001248748, NP_001248749, NP_001248750, NP_001353252, NP_001353253, NP_001353254, NP_001353255, NP_001353256, NP_001353257, NP_001353258, NP_001353259, NP_001353260, NP_001353261, NP_001357616, NP_061149 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008862	Tcp11	Family

Pfam: PF05794

UniProt features (15 total): splice variant 6, sequence variant 2, region of interest 2, compositionally biased region 2, chain 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWU5-F1	78.50	0.53

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 86 (showing top): GOBP_REGULATION_OF_CELL_MATURATION, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MALE_GAMETE_GENERATION, GOBP_SPERM_CAPACITATION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_CELL_MATURATION, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GNF2_CCNA1, AACTTT_UNKNOWN, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, WEBER_METHYLATED_HCP_IN_SPERM_UP, GOBP_REGULATION_OF_CELL_DEVELOPMENT

GO Biological Process (6): adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), germ cell development (GO:0007281), spermatogenesis (GO:0007283), obsolete protein kinase A signaling (GO:0010737), regulation of sperm capacitation (GO:1902490), cell differentiation (GO:0030154)

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

GO Cellular Component (8): acrosomal vesicle (GO:0001669), membrane (GO:0016020), sperm flagellum (GO:0036126), sperm midpiece (GO:0097225), cilium (GO:0005929), cytoplasmic vesicle (GO:0031410), 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
developmental process involved in reproduction	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
male gamete generation	1
sperm capacitation	1
regulation of multicellular organismal process	1
regulation of cell maturation	1
regulation of reproductive process	1
cellular developmental process	1
binding	1
secretory granule	1
9+2 motile cilium	1
sperm flagellum	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoplasm	1
intracellular vesicle	1
cilium	1

Protein interactions and networks

STRING

704 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCP11	ZNF76	P36508	975
TCP11	ZNF143	P52747	891
TCP11	SCUBE3	Q8IX30	665
TCP11	ANKS1A	Q92625	630
TCP11	TEKT3	Q9BXF9	624
TCP11	TAF11	Q15544	574
TCP11	FANCE	Q9HB96	566
TCP11	SPATA3	Q8NHX4	531
TCP11	KLHL35	Q6PF15	510
TCP11	FNTA	P49354	508
TCP11	SPATA31E1	Q6ZUB1	507
TCP11	LRRC37A	A6NMS7	496
TCP11	LRRC37A3	O60309	495
TCP11	DRC5	Q5JU00	493
TCP11	Q12799	Q12799	480

IntAct

2 interactions, top by confidence:

A	B	Type	Score
VAV2	TCP11	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): TCP11 (Two-hybrid), TCP11 (Two-hybrid), TCP11 (Two-hybrid), NPFFR1 (Two-hybrid), LMBRD1 (Two-hybrid), MAP2K1 (Two-hybrid), FANCF (Two-hybrid), GRAPL (Two-hybrid), ZNF688 (Two-hybrid), KRTAP13-3 (Two-hybrid), TCP11 (Reconstituted Complex), TCP11 (Two-hybrid), APP (Reconstituted Complex)

ESM2 similar proteins: A2AV37, A2BID5, A2VDR8, A7E2Y6, A7Z033, B4DZS4, O15068, O35821, O60645, O70576, O94812, P52630, P83436, Q01755, Q03169, Q08CY4, Q0P4Q0, Q0V8C2, Q14746, Q15021, Q17RC7, Q19262, Q1LXZ7, Q2TBH9, Q3T1G7, Q3TBD2, Q3UM29, Q5H9J9, Q5XI00, Q61333, Q62825, Q63406, Q64096, Q6DIA2, Q6GPP1, Q6KAR6, Q7T006, Q80TT2, Q80VA5, Q8K1H7

Diamond homologs: A7Z033, B4DZS4, Q01755, Q568Z0, Q5H9J9, Q5XI00, Q8BTG3, Q8K1H7, Q8N4U5, Q8WWU5, Q9NUJ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1521 predictions. Top by Δscore:

Variant	Effect	Δscore
6:35120153:GCTCA:G	donor_loss	1.0000
6:35120154:CTCA:C	donor_loss	1.0000
6:35120155:TCA:T	donor_loss	1.0000
6:35120156:CA:C	donor_loss	1.0000
6:35120158:C:CT	donor_loss	1.0000
6:35120253:TGGC:T	donor_gain	1.0000
6:35120338:GGTC:G	acceptor_loss	1.0000
6:35120341:C:CC	acceptor_gain	1.0000
6:35120341:CTGGG:C	acceptor_loss	1.0000
6:35120342:T:C	acceptor_loss	1.0000
6:35120349:C:CT	acceptor_gain	1.0000
6:35120349:C:T	acceptor_gain	1.0000
6:35120350:A:T	acceptor_gain	1.0000
6:35120423:TCCTA:T	donor_loss	1.0000
6:35120424:CCTAC:C	donor_loss	1.0000
6:35120425:CTACC:C	donor_loss	1.0000
6:35120426:TAC:T	donor_loss	1.0000
6:35120427:A:AT	donor_loss	1.0000
6:35120428:C:G	donor_loss	1.0000
6:35120907:A:AC	donor_gain	1.0000
6:35120908:C:CC	donor_gain	1.0000
6:35120908:CT:C	donor_gain	1.0000
6:35120908:CTAG:C	donor_gain	1.0000
6:35120908:CTAGG:C	donor_gain	1.0000
6:35120919:A:AC	donor_gain	1.0000
6:35120929:T:TA	donor_gain	1.0000
6:35120951:A:AC	donor_gain	1.0000
6:35120952:C:CC	donor_gain	1.0000
6:35120965:T:TA	donor_gain	1.0000
6:35121041:TCCCT:T	acceptor_gain	1.0000

AlphaMissense

3388 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:35118482:A:C	F433L	0.973
6:35118482:A:T	F433L	0.973
6:35118484:A:G	F433L	0.973
6:35120623:A:G	W247R	0.972
6:35120623:A:T	W247R	0.972
6:35118347:A:C	F478L	0.966
6:35118347:A:T	F478L	0.966
6:35118349:A:G	F478L	0.966
6:35118495:C:G	R429P	0.962
6:35120621:C:A	W247C	0.951
6:35120621:C:G	W247C	0.951
6:35120934:G:C	F230L	0.951
6:35120934:G:T	F230L	0.951
6:35120936:A:G	F230L	0.951
6:35120619:A:G	L248P	0.949
6:35120479:C:G	G295R	0.941
6:35118480:A:G	L434P	0.940
6:35118402:A:G	L460P	0.929
6:35118483:A:G	F433S	0.918
6:35119272:A:G	L412P	0.918
6:35119284:A:G	L408P	0.916
6:35120478:C:T	G295D	0.915
6:35118390:C:T	G464D	0.914
6:35118423:A:G	L453P	0.914
6:35120474:G:C	F296L	0.914
6:35120474:G:T	F296L	0.914
6:35120476:A:G	F296L	0.914
6:35129143:A:C	F92L	0.909
6:35129143:A:T	F92L	0.909
6:35129145:A:G	F92L	0.909

dbSNP variants (sampled 300 via entrez): RS1000157570 (6:35141931 G>C,T), RS1000264480 (6:35135429 A>G), RS1000314905 (6:35140817 G>A,C,T), RS1000603265 (6:35140692 C>A,T), RS1000897337 (6:35120735 T>C), RS1001007524 (6:35137693 T>C), RS1001037535 (6:35134624 A>G), RS1001051341 (6:35141898 G>A), RS1001334076 (6:35127919 T>C), RS1001350890 (6:35129422 T>C), RS1001657261 (6:35142216 C>T), RS1001688587 (6:35142505 A>C,G), RS1001821305 (6:35121518 G>A), RS1001908126 (6:35136281 C>T), RS1002223547 (6:35127595 T>G)

Disease associations

OMIM: gene MIM:186982 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000175_47	Height	4.000000e-08
GCST005752_31	Systemic lupus erythematosus	7.000000e-08
GCST005752_42	Systemic lupus erythematosus	2.000000e-06
GCST007798_49	Asthma	8.000000e-09
GCST007800_85	Asthma (childhood onset)	1.000000e-07
GCST008163_19	Height	4.000000e-06
GCST008163_334	Height	1.000000e-08
GCST010242_324	HDL cholesterol levels	1.000000e-13
GCST010702_101	Subcortical volume (MOSTest)	2.000000e-08
GCST010703_346	Brain morphology (MOSTest)	4.000000e-10
GCST010989_269	Body size at age 10	2.000000e-09
GCST012227_968	Hip circumference adjusted for BMI	4.000000e-10
GCST90013406_153	Liver enzyme levels (alkaline phosphatase)	5.000000e-22
GCST90020028_682	Hip circumference adjusted for BMI	1.000000e-08
GCST90020028_684	Hip circumference adjusted for BMI	3.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004346	neuroimaging measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008039	BMI-adjusted hip circumference
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	decreases expression, affects cotreatment	1
Leflunomide	increases expression	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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