PIERCE1

Summary

PIERCE1 (piercer of microtubule wall 1, HGNC:28435) is a protein-coding gene on chromosome 9q34.3, encoding Piercer of microtubule wall 1 protein (Q5BN46). Microtubule inner protein involved in the attachment of outer dynein arms (ODAs) to dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Predicted to be involved in axoneme assembly; establishment of left/right asymmetry; and flagellated sperm motility. Predicted to act upstream of or within DNA damage response; cellular response to UV-C; and regulation of gene expression. Located in axonemal microtubule.

Source: NCBI Gene 138162 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 6 total
• MANE Select transcript: NM_001048265

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28435
Approved symbol	PIERCE1
Name	piercer of microtubule wall 1
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC29761, RbEST47
Ensembl gene	ENSG00000160345
Ensembl biotype	protein_coding
OMIM	614502
Entrez	138162

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000371786, ENST00000371789, ENST00000371791, ENST00000419770, ENST00000429260, ENST00000862731, ENST00000931412, ENST00000931413, ENST00000931414

RefSeq mRNA: 2 — MANE Select: NM_001048265 NM_001048265, NM_144654

CCDS: CCDS43899, CCDS6989

Canonical transcript exons

ENST00000429260 — 3 exons

Exon	Start	End
ENSE00001051627	135498585	135498663
ENSE00001793908	135499709	135499869
ENSE00001918417	135495181	135495615

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.9712 / max 129.9125, expressed in 1472 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103090	6.0455	1414
103092	0.8074	383
103093	0.0614	25
103089	0.0569	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.06	gold quality
epithelium of bronchus	UBERON:0002031	98.70	gold quality
right uterine tube	UBERON:0001302	98.68	gold quality
bronchus	UBERON:0002185	97.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.39	gold quality
left testis	UBERON:0004533	94.22	gold quality
right testis	UBERON:0004534	93.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.20	gold quality
testis	UBERON:0000473	91.70	gold quality
nasal cavity epithelium	UBERON:0005384	90.80	gold quality
caput epididymis	UBERON:0004358	88.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.21	gold quality
adult organism	UBERON:0007023	87.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.09	gold quality
right adrenal gland	UBERON:0001233	85.48	gold quality
adenohypophysis	UBERON:0002196	85.33	gold quality
right adrenal gland cortex	UBERON:0035827	85.23	gold quality
left adrenal gland	UBERON:0001234	84.58	gold quality
left adrenal gland cortex	UBERON:0035825	84.57	gold quality
nucleus accumbens	UBERON:0001882	84.26	gold quality
caudate nucleus	UBERON:0001873	84.01	gold quality
nasal cavity mucosa	UBERON:0001826	83.90	gold quality
pituitary gland	UBERON:0000007	83.43	gold quality
epithelium of nasopharynx	UBERON:0001951	83.23	gold quality
adrenal cortex	UBERON:0001235	82.61	gold quality
anterior cingulate cortex	UBERON:0009835	82.38	gold quality
cingulate cortex	UBERON:0003027	82.33	gold quality
hypothalamus	UBERON:0001898	81.71	gold quality
adrenal gland	UBERON:0002369	81.35	gold quality
right frontal lobe	UBERON:0002810	81.25	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	64.26
E-HCAD-1	yes	32.70
E-MTAB-10287	yes	28.18
E-MTAB-6701	yes	15.70
E-GEOD-130148	yes	13.13
E-MTAB-9388	yes	6.89
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

29 targeting PIERCE1, 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-6748-5P	100.00	65.81	1057
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-582-3P	96.69	67.38	1019
HSA-MIR-12128	96.67	66.98	1471
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-576-3P	96.14	65.63	773
HSA-MIR-6735-3P	96.10	63.81	600
HSA-MIR-6767-5P	90.00	62.41	97
HSA-MIR-4750-5P	80.79	59.79	18

Literature-anchored findings (GeneRIF, showing 1)

• Divergence of the PIERCE1 expression between mice and humans as a p53 target gene. (PMID:32745107)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pierce1	ENSDARG00000058940
mus_musculus	Pierce1	ENSMUSG00000026831
rattus_norvegicus	Pierce1	ENSRNOG00000010152
drosophila_melanogaster	CG34107	FBGN0083943

Paralogs (1): PIERCE2 (ENSG00000261652)

Protein

Protein identifiers

Piercer of microtubule wall 1 protein — Q5BN46 (reviewed: Q5BN46)

Alternative names: UPF0691 protein C9orf116, p53-induced expression in RB-null cells protein 1

All UniProt accessions (2): Q5BN46, H0Y549

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule inner protein involved in the attachment of outer dynein arms (ODAs) to dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. Functions at the initial step of left-right asymmetry specification of the visceral organs.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Interacts with CFAP53, ODAD1 and ODAD3; the interactions link the outer dynein arms docking complex (ODA-DC) to the internal microtubule inner proteins (MIP) in cilium axoneme.

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

Tissue specificity. Expressed in airway epithelial cells.

Similarity. Belongs to the PIERCE1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5BN46-1	1	yes
Q5BN46-2	2

RefSeq proteins (2): NP_001041730, NP_653255 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026507	PIRC1/2	Family

Pfam: PF14892

UniProt features (4 total): splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7UNG	ELECTRON MICROSCOPY	3.6
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5BN46-F1	77.39	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 123 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_RESPONSE_TO_UV_C, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_SPECIFICATION_OF_SYMMETRY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, SMID_BREAST_CANCER_LUMINAL_B_UP, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_RESPONSE_TO_UV, GOBP_DNA_DAMAGE_RESPONSE, GOBP_RESPONSE_TO_RADIATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION

GO Biological Process (8): cilium movement (GO:0003341), DNA damage response (GO:0006974), determination of left/right symmetry (GO:0007368), regulation of gene expression (GO:0010468), flagellated sperm motility (GO:0030317), axoneme assembly (GO:0035082), establishment of left/right asymmetry (GO:0061966), cellular response to UV-C (GO:0071494)

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

GO Cellular Component (9): nucleus (GO:0005634), cytoplasm (GO:0005737), axonemal microtubule (GO:0005879), sperm flagellum (GO:0036126), axonemal A tubule inner sheath (GO:0160111), 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
microtubule-based movement	1
cellular response to stress	1
determination of bilateral symmetry	1
left/right pattern formation	1
gene expression	1
regulation of macromolecule biosynthetic process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
determination of left/right symmetry	1
response to UV-C	1
cellular response to UV	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasmic microtubule	1
axoneme	1
9+2 motile cilium	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	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

1416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIERCE1	CFAP90	A4QMS7	727
PIERCE1	CFAP96	A7E2U8	593
PIERCE1	CFAP184	Q2M329	580
PIERCE1	CLXN	Q9HAE3	575
PIERCE1	SOWAHA	Q2M3V2	549
PIERCE1	IQUB	Q8NA54	544
PIERCE1	TEKTIP1	A6NCJ1	506
PIERCE1	ARMC3	Q5W041	493
PIERCE1	KRT80	Q6KB66	447
PIERCE1	PIERCE2	H3BRN8	447
PIERCE1	VSTM2L	Q96N03	443
PIERCE1	DAND5	Q8N907	438
PIERCE1	IFT57	Q9NWB7	432
PIERCE1	CCDC170	Q8IYT3	377
PIERCE1	IQCF3	P0C7M6	376

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PIERCE1	FHL3	psi-mi:“MI:0915”(physical association)	0.560
FHL3	PIERCE1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (3): C9orf116 (Two-hybrid), HSPA8 (Affinity Capture-MS), FHL3 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTD5, A0A1B0GUX0, A0A3Q1MT14, A4D263, A6NL82, A6QQL5, A8QW39, B0UXH9, B5X5D0, B9EJX3, E1B9R1, F1MMV1, Q148A4, Q1JPL0, Q2T9T0, Q32KQ1, Q32L72, Q32L77, Q32P67, Q3V0J4, Q5BN46, Q5NC57, Q5NC83, Q5SPV6, Q5SS90, Q5SVJ3, Q5VTT2, Q5VZQ5, Q66HC0, Q66HR9, Q6AYM0, Q6NXP0, Q6P3G4, Q6ZVS7, Q80X60, Q8CDT5, Q8CDU5, Q8N5S3, Q8N7U6, Q8N865

Diamond homologs: B0UXH9, B5X5D0, Q32P67, Q5BN45, Q5BN46

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

756 predictions. Top by Δscore:

Variant	Effect	Δscore
9:135495612:CTTT:C	acceptor_gain	1.0000
9:135498583:A:AC	donor_gain	1.0000
9:135498584:C:CC	donor_gain	1.0000
9:135499524:T:TA	donor_gain	1.0000
9:135495613:TTT:T	acceptor_gain	0.9900
9:135495614:TT:T	acceptor_gain	0.9900
9:135495615:TC:T	acceptor_loss	0.9900
9:135495616:C:CC	acceptor_gain	0.9900
9:135495616:CT:C	acceptor_loss	0.9900
9:135498584:CAGG:C	donor_gain	0.9900
9:135499525:C:A	donor_gain	0.9900
9:135499561:A:AC	donor_gain	0.9900
9:135499562:C:CC	donor_gain	0.9900
9:135499744:G:A	donor_gain	0.9900
9:135500112:G:GT	donor_gain	0.9900
9:135500171:GGGTT:G	donor_gain	0.9900
9:135500172:GGTT:G	donor_gain	0.9900
9:135500238:G:T	donor_gain	0.9900
9:135501121:CCGG:C	donor_loss	0.9900
9:135501125:T:A	donor_loss	0.9900
9:135496407:T:A	donor_gain	0.9800
9:135498583:ACAGG:A	donor_gain	0.9800
9:135498584:CAGGC:C	donor_gain	0.9800
9:135498664:C:CC	acceptor_gain	0.9800
9:135499702:T:TA	donor_gain	0.9800
9:135499723:C:CT	donor_gain	0.9800
9:135500168:ACGGG:A	donor_gain	0.9800
9:135500202:C:T	donor_gain	0.9800
9:135500835:G:T	donor_gain	0.9800
9:135501124:G:GG	donor_gain	0.9800

AlphaMissense

901 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:135499738:G:C	F38L	0.985
9:135499738:G:T	F38L	0.985
9:135499740:A:G	F38L	0.985
9:135499739:A:G	F38S	0.964
9:135495607:A:C	F77L	0.961
9:135495607:A:T	F77L	0.961
9:135495609:A:G	F77L	0.961
9:135495469:G:C	F123L	0.959
9:135495469:G:T	F123L	0.959
9:135495471:A:G	F123L	0.959
9:135498616:C:T	G64E	0.959
9:135495586:A:C	F84L	0.957
9:135495586:A:T	F84L	0.957
9:135495588:A:G	F84L	0.957
9:135498604:G:T	P68H	0.951
9:135498630:A:C	S59R	0.946
9:135498630:A:T	S59R	0.946
9:135498632:T:G	S59R	0.946
9:135499720:G:C	F44L	0.944
9:135499720:G:T	F44L	0.944
9:135499722:A:G	F44L	0.944
9:135495460:A:C	S126R	0.943
9:135495460:A:T	S126R	0.943
9:135495462:T:G	S126R	0.943
9:135495538:A:C	N100K	0.942
9:135495538:A:T	N100K	0.942
9:135498617:C:A	G64W	0.942
9:135498641:A:C	Y56D	0.938
9:135499741:C:A	R37S	0.938
9:135499741:C:G	R37S	0.938

dbSNP variants (sampled 300 via entrez): RS1000080091 (9:135497044 G>A,C,T), RS1000785408 (9:135499272 G>A), RS1001673151 (9:135499651 C>T), RS1001704060 (9:135499190 C>T), RS1001821806 (9:135495548 T>C), RS1002053474 (9:135500003 C>A,G,T), RS1002312299 (9:135494953 T>C), RS1002708703 (9:135497857 G>A,C), RS1002828368 (9:135496914 A>G), RS1003920820 (9:135500090 G>A,T), RS1003961470 (9:135497330 T>C), RS1004295471 (9:135497524 A>G), RS1006232056 (9:135501050 G>A), RS1006263169 (9:135501288 A>C), RS1006411223 (9:135501616 C>A,G,T)

Disease associations

OMIM: gene MIM:614502 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1180	Metabolite levels	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010454	adenosine monophosphate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	5
Air Pollutants	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	increases expression, decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Ethinyl Estradiol	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Tunicamycin	increases expression	1
Urethane	decreases expression	1
Zidovudine	decreases expression, affects cotreatment	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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