TTC29

Summary

TTC29 (tetratricopeptide repeat domain 29, HGNC:29936) is a protein-coding gene on chromosome 4q31.22, encoding Tetratricopeptide repeat protein 29 (Q8NA56). Axonemal protein which is implicated in axonemal and/or peri-axonemal structure assembly and regulates flagellum assembly and beating and therefore sperm motility.

Involved in cilium movement and cilium organization. Located in sperm flagellum. Implicated in spermatogenic failure 42.

Source: NCBI Gene 83894 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 42 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 90 total — 8 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 8
• MANE Select transcript: NM_031956

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29936
Approved symbol	TTC29
Name	tetratricopeptide repeat domain 29
Location	4q31.22
Locus type	gene with protein product
Status	Approved
Aliases	NYD-SP14
Ensembl gene	ENSG00000137473
Ensembl biotype	protein_coding
OMIM	618735
Entrez	83894

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000325106, ENST00000502319, ENST00000504272, ENST00000504425, ENST00000506019, ENST00000508306, ENST00000513335, ENST00000515315, ENST00000873385, ENST00000873386, ENST00000873387

RefSeq mRNA: 3 — MANE Select: NM_031956 NM_001300761, NM_001317806, NM_031956

CCDS: CCDS47141, CCDS75200, CCDS82965

Canonical transcript exons

ENST00000325106 — 13 exons

Exon	Start	End
ENSE00001000656	146937594	146937677
ENSE00001082014	146867498	146867583
ENSE00001082015	146833806	146833897
ENSE00001082016	146903544	146903729
ENSE00001082017	146909026	146909249
ENSE00001082019	146874716	146874928
ENSE00001228247	146945031	146945077
ENSE00001535410	146706617	146707188
ENSE00003501957	146820125	146820248
ENSE00003504638	146803457	146803685
ENSE00003596557	146939804	146939901
ENSE00003686406	146707485	146707551
ENSE00003913445	146945709	146945864

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 95.98.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9732 / max 169.6080, expressed in 254 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54265	0.5818	171
54264	0.2438	85
54266	0.1391	63
54263	0.0085	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.98	gold quality
bronchial epithelial cell	CL:0002328	95.77	gold quality
left testis	UBERON:0004533	94.71	gold quality
right testis	UBERON:0004534	94.47	gold quality
bronchus	UBERON:0002185	94.21	gold quality
testis	UBERON:0000473	92.06	gold quality
right uterine tube	UBERON:0001302	89.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.66	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.46	gold quality
oviduct epithelium	UBERON:0004804	86.74	gold quality
adult organism	UBERON:0007023	84.68	gold quality
fallopian tube	UBERON:0003889	77.61	gold quality
epithelium of nasopharynx	UBERON:0001951	77.27	gold quality
nasal cavity mucosa	UBERON:0001826	68.33	gold quality
caput epididymis	UBERON:0004358	64.87	gold quality
nasal cavity epithelium	UBERON:0005384	63.71	silver quality
right lung	UBERON:0002167	62.76	gold quality
ventricular zone	UBERON:0003053	60.39	gold quality
trachea	UBERON:0003126	57.06	silver quality
corpus epididymis	UBERON:0004359	56.88	gold quality
corpus callosum	UBERON:0002336	54.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
hypothalamus	UBERON:0001898	54.26	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
endometrium	UBERON:0001295	53.94	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
stromal cell of endometrium	CL:0002255	53.86	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
epithelial cell of pancreas	CL:0000083	53.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting TTC29, 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-3134	100.00	66.43	777
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-100-3P	99.20	67.33	672
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-3145-3P	98.85	69.07	2031

Literature-anchored findings (GeneRIF, showing 3)

• TTC29 expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• Mutations in TTC29 results in Asthenozoospermia and Male Infertility. (PMID:31735292)
• Novel axonemal protein ZMYND12 interacts with TTC29 and DNAH1, and is required for male fertility and flagellum function. (PMID:37934199)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttc29	ENSDARG00000058885
mus_musculus	Ttc29	ENSMUSG00000037101
rattus_norvegicus	Ttc29	ENSRNOG00000012342

Paralogs (6): TTC28 (ENSG00000100154), GPSM2 (ENSG00000121957), GPSM1 (ENSG00000160360), RAPSN (ENSG00000165917), TTC24 (ENSG00000187862), GPSM3 (ENSG00000213654)

Protein

Protein identifiers

Tetratricopeptide repeat protein 29 — Q8NA56 (reviewed: Q8NA56)

Alternative names: Protein TBPP2A, Testis development protein NYD-SP14

All UniProt accessions (7): Q8NA56, A0A140VK62, D6R945, D6RJF6, E7EQ14, E7EQZ6, G5E9Z5

UniProt curated annotations — full annotation on UniProt →

Function. Axonemal protein which is implicated in axonemal and/or peri-axonemal structure assembly and regulates flagellum assembly and beating and therefore sperm motility.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme.

Tissue specificity. Expressed in spermatozoa (at protein level).

Disease relevance. Spermatogenic failure 42 (SPGF42) [MIM:618745] An autosomal recessive infertility disorder characterized by almost immotile spermatozoa due to multiple morphologic abnormalities of the flagella, including short, absent, coiled, and bent flagella. Some spermatozoa also show abnormalities of the head, acrosome, midpiece, or endpiece. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The TPR repeats are required for axonemal localization and flagellar beating.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NA56-1	1	yes
Q8NA56-2	2

RefSeq proteins (3): NP_001287690, NP_001304735, NP_114162* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR051476	Bac_ResReg_Asp_Phosphatase	Family

Pfam: PF13424, PF13432

UniProt features (17 total): repeat 7, sequence variant 5, chain 1, splice variant 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NA56-F1	84.86	0.64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): NKX62_Q2, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CELL_PROJECTION_ORGANIZATION, YNGTTNNNATT_UNKNOWN, GOCC_MOTILE_CILIUM, GOCC_SPERM_PRINCIPAL_PIECE, GOCC_CILIUM, EVI1_02, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOCC_9PLUS2_MOTILE_CILIUM, GSE13522_CTRL_VS_T_CRUZI_BRAZIL_STRAIN_INF_SKIN_UP, SRSF9_TARGET_GENES, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2

GO Biological Process (2): cilium movement (GO:0003341), cilium organization (GO:0044782)

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

GO Cellular Component (6): 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	2
microtubule-based movement	1
organelle organization	1
plasma membrane bounded cell projection organization	1
binding	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
cilium	1

Protein interactions and networks

STRING

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTC29	DNAH1	Q9P2D7	760
TTC29	TTC21A	Q8NDW8	706
TTC29	CFAP43	Q8NDM7	679
TTC29	CFAP44	Q96MT7	661
TTC29	CFAP91	Q7Z4T9	646
TTC29	CEP135	Q66GS9	645
TTC29	QRICH2	Q9H0J4	636
TTC29	CFAP70	Q5T0N1	630
TTC29	CFAP58	Q5T655	629
TTC29	CFAP69	A5D8W1	627
TTC29	ARMC2	Q8NEN0	626
TTC29	FSIP2	Q5CZC0	615
TTC29	DNAH8	Q96JB1	614
TTC29	CFAP251	Q8TBY9	612
TTC29	CFAP47	Q6ZTR5	612

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TTC29	OBSL1	psi-mi:“MI:0914”(association)	0.350
CSNK2B	TUBAL3	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): TTC29 (Affinity Capture-MS), LSG1 (Affinity Capture-MS), EIF5B (Affinity Capture-MS), DHX16 (Affinity Capture-MS), ANKFY1 (Affinity Capture-MS), OBSL1 (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), CDK18 (Affinity Capture-MS), FBXW8 (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), IKBIP (Affinity Capture-MS), MACF1 (Affinity Capture-MS), CSTF2 (Affinity Capture-MS), NELFE (Affinity Capture-MS), TAF8 (Affinity Capture-MS)

ESM2 similar proteins: A1A5P5, A1L1K3, A7SUU7, B4JHK2, B4NKT1, E9Q6P5, F1QN74, P09913, P50748, Q0P5W1, Q14CX7, Q294E0, Q2KI89, Q32NR4, Q32PH0, Q3U0M1, Q4R6I5, Q4R6M4, Q5R629, Q5RE52, Q5U249, Q5ZKK3, Q60462, Q68F70, Q6AYP3, Q6PA97, Q6QI44, Q80VM3, Q86TV6, Q8BGB2, Q8BH74, Q8BTZ4, Q8BWZ3, Q8C0S4, Q8CIM8, Q8GZN1, Q8IYW2, Q8JGR7, Q8K368, Q8N3P4

Diamond homologs: Q32NR4, Q4R6M4, Q6AYP3, Q80VM3, Q8NA56

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	4
Uncertain significance	66
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1455428	NC_000004.11:g.(?146560292)(149358012_?)del	Pathogenic
2442621	NM_031956.4(TTC29):c.176+1G>A	Pathogenic
805956	NM_031956.4(TTC29):c.*334G>A	Pathogenic
805957	NM_031956.4(TTC29):c.330_334del (p.Glu111fs)	Pathogenic
805958	NM_031956.4(TTC29):c.750C>A (p.Tyr250Ter)	Pathogenic
805959	NM_031956.4(TTC29):c.1107C>G (p.Tyr369Ter)	Pathogenic
805960	NM_031956.4(TTC29):c.412_425del (p.Asp138fs)	Pathogenic
805961	NM_031956.4(TTC29):c.977+1G>T	Pathogenic
1675966	NM_031956.4(TTC29):c.754C>T (p.Gln252Ter)	Likely pathogenic
3075967	NM_031956.4(TTC29):c.217_221del (p.Leu73fs)	Likely pathogenic
3350480	NM_031956.4(TTC29):c.800-1G>A	Likely pathogenic
4533232	NM_031956.4(TTC29):c.58C>T (p.Gln20Ter)	Likely pathogenic

SpliceAI

3266 predictions. Top by Δscore:

Variant	Effect	Δscore
4:146707484:CCTA:C	donor_gain	1.0000
4:146707487:A:AC	donor_gain	1.0000
4:146707488:C:CC	donor_gain	1.0000
4:146707547:CTCTT:C	acceptor_gain	1.0000
4:146707549:CTT:C	acceptor_gain	1.0000
4:146707552:C:CC	acceptor_gain	1.0000
4:146803451:CCTTA:C	donor_loss	1.0000
4:146803453:TTA:T	donor_loss	1.0000
4:146803455:A:AC	donor_gain	1.0000
4:146803455:A:AT	donor_loss	1.0000
4:146803456:C:CC	donor_gain	1.0000
4:146833801:CTTA:C	donor_loss	1.0000
4:146833802:TTA:T	donor_loss	1.0000
4:146833803:TA:T	donor_loss	1.0000
4:146833804:A:T	donor_loss	1.0000
4:146833805:C:T	donor_loss	1.0000
4:146833805:CCT:C	donor_gain	1.0000
4:146867496:A:AC	donor_gain	1.0000
4:146867497:C:CC	donor_gain	1.0000
4:146903730:C:CC	acceptor_gain	1.0000
4:146903733:C:CT	acceptor_gain	1.0000
4:146909021:CTTA:C	donor_loss	1.0000
4:146909022:TTA:T	donor_loss	1.0000
4:146909023:TA:T	donor_loss	1.0000
4:146909024:A:AC	donor_gain	1.0000
4:146909024:A:AT	donor_loss	1.0000
4:146909025:C:CC	donor_gain	1.0000
4:146909025:C:CG	donor_loss	1.0000
4:146909025:CCTTT:C	donor_gain	1.0000
4:146909245:TATAA:T	acceptor_gain	1.0000

AlphaMissense

3152 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:146833822:C:G	A321P	0.983
4:146820145:C:A	G361W	0.981
4:146820144:C:T	G361E	0.978
4:146803574:C:G	A405P	0.976
4:146803580:C:G	A403P	0.974
4:146833821:G:T	A321D	0.974
4:146867541:C:T	G281D	0.974
4:146820145:C:G	G361R	0.972
4:146820145:C:T	G361R	0.972
4:146867536:C:G	A283P	0.970
4:146867542:C:G	G281R	0.969
4:146909183:G:C	F81L	0.969
4:146909183:G:T	F81L	0.969
4:146909185:A:G	F81L	0.969
4:146803670:C:G	A373P	0.963
4:146820144:C:A	G361V	0.963
4:146874914:C:G	A201P	0.957
4:146909047:C:G	A127P	0.957
4:146833828:C:G	A319P	0.956
4:146803669:G:T	A373D	0.955
4:146874817:A:G	L233P	0.954
4:146803579:G:T	A403E	0.953
4:146803649:C:G	A380P	0.951
4:146820160:C:G	A356P	0.951
4:146833812:A:G	L324P	0.950
4:146867505:G:T	A293E	0.950
4:146803507:A:G	L427P	0.948
4:146820229:C:G	A333P	0.948
4:146874737:C:G	A260P	0.947
4:146803499:A:G	W430R	0.946

dbSNP variants (sampled 300 via entrez): RS1000009070 (4:146864235 C>T), RS1000012200 (4:146754096 G>T), RS1000013427 (4:146905125 A>G), RS1000038633 (4:146864065 T>C), RS1000048617 (4:146868986 T>C), RS1000060784 (4:146821027 A>G), RS1000067245 (4:146798853 C>A,T), RS1000077728 (4:146911957 A>G), RS1000100802 (4:146784446 T>C), RS1000124760 (4:146892276 G>A,C), RS1000129693 (4:146911703 A>G), RS10001365 (4:146876062 G>A,T), RS1000142585 (4:146899427 A>C,T), RS1000145417 (4:146805674 GA>G), RS1000148773 (4:146767592 G>A)

Disease associations

OMIM: gene MIM:618735 | disease phenotypes: MIM:251100, MIM:618745

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 42	Strong	Autosomal recessive
non-syndromic male infertility due to sperm motility disorder	Supportive	Autosomal recessive

Mondo (3): methylmalonic aciduria, cblA type (MONDO:0009613), spermatogenic failure 42 (MONDO:0032896), (MONDO:0017173)

Orphanet (3): Vitamin B12-responsive methylmalonic acidemia (Orphanet:28), Vitamin B12-responsive methylmalonic acidemia type cblA (Orphanet:79310), Male infertility with spermatogenesis disorder (Orphanet:399775)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0012207	Reduced sperm motility
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0032561	Microcephalic sperm head
HP:0032562	Tapered sperm head

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002360_8	Plasma amyloid beta peptide concentrations (ABx-40)	2.000000e-06
GCST002935_12	Lead levels	2.000000e-06
GCST007096_83	Pulse pressure	4.000000e-16
GCST007097_126	Pulse pressure	7.000000e-06
GCST007097_127	Pulse pressure	2.000000e-06
GCST007099_72	Systolic blood pressure	2.000000e-09
GCST007327_219	Smoking status (ever vs never smokers)	1.000000e-13
GCST008810_90	Smoking initiation (ever regular vs never regular)	2.000000e-10
GCST010479_70	Coronary artery disease	2.000000e-12
GCST010574_6	Evening vs. morning chronotype (self-assessed)	1.000000e-06
GCST010725_4	Malaria	4.000000e-10
GCST010725_84	Malaria	7.000000e-11
GCST010725_89	Malaria	7.000000e-11
GCST010867_30	Coronary artery disease	8.000000e-11
GCST011703_68	Smoking initiation	3.000000e-13

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005659	plasma beta-amyloid 1-40 measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0004318	smoking behavior
EFO:0005670	smoking initiation
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	8
belinostat	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
methylmercuric chloride	decreases expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
trichostatin A	increases expression	1
entinostat	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Methotrexate	increases expression	1
Smoke	increases abundance, increases expression	1
Triclosan	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns