PIERCE2

Summary

PIERCE2 (piercer of microtubule wall 2, HGNC:44654) is a protein-coding gene on chromosome 15q21.3, encoding Piercer of microtubule wall 2 protein (H3BRN8). 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; determination of left/right symmetry; and flagellated sperm motility. Located in axonemal microtubule.

Source: NCBI Gene 145788 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001198784

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44654
Approved symbol	PIERCE2
Name	piercer of microtubule wall 2
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ27352
Ensembl gene	ENSG00000261652
Ensembl biotype	protein_coding
OMIM	619669
Entrez	145788

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000569691, ENST00000570794

RefSeq mRNA: 1 — MANE Select: NM_001198784 NM_001198784

CCDS: CCDS58363

Canonical transcript exons

ENST00000569691 — 2 exons

Exon	Start	End
ENSE00002575969	55408495	55408786
ENSE00002624403	55418223	55418798

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 93.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2836 / max 52.0519, expressed in 1315 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146765	1.5413	854
146768	1.1716	668
146766	0.3191	183
146767	0.2516	118

Top tissues by expression

249 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	93.37	gold quality
bronchial epithelial cell	CL:0002328	93.05	gold quality
bronchus	UBERON:0002185	91.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.61	gold quality
right uterine tube	UBERON:0001302	84.56	gold quality
sperm	CL:0000019	81.59	gold quality
body of pancreas	UBERON:0001150	80.85	gold quality
left ventricle myocardium	UBERON:0006566	80.73	gold quality
myocardium	UBERON:0002349	80.64	silver quality
caput epididymis	UBERON:0004358	80.63	gold quality
heart right ventricle	UBERON:0002080	79.88	gold quality
oocyte	CL:0000023	79.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.97	gold quality
pancreas	UBERON:0001264	77.69	gold quality
kidney epithelium	UBERON:0004819	77.48	silver quality
parotid gland	UBERON:0001831	77.26	gold quality
secondary oocyte	CL:0000655	76.88	gold quality
pituitary gland	UBERON:0000007	76.86	gold quality
adenohypophysis	UBERON:0002196	76.81	gold quality
ganglionic eminence	UBERON:0004023	76.68	gold quality
gastrocnemius	UBERON:0001388	76.59	gold quality
left testis	UBERON:0004533	76.49	gold quality
right testis	UBERON:0004534	76.38	gold quality
heart left ventricle	UBERON:0002084	76.26	gold quality
cardiac ventricle	UBERON:0002082	76.14	gold quality
testis	UBERON:0000473	75.81	gold quality
oviduct epithelium	UBERON:0004804	75.76	gold quality
islet of Langerhans	UBERON:0000006	75.69	gold quality
mucosa of transverse colon	UBERON:0004991	75.65	gold quality
muscle of leg	UBERON:0001383	75.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting PIERCE2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-217-3P	95.67	68.42	1000

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pierce2	ENSMUSG00000086158
rattus_norvegicus	Pierce2	ENSRNOG00000052869
drosophila_melanogaster	CG34107	FBGN0083943

Paralogs (1): PIERCE1 (ENSG00000160345)

Protein

Protein identifiers

Piercer of microtubule wall 2 protein — H3BRN8 (reviewed: H3BRN8)

All UniProt accessions (2): H3BRN8, A0A9L9PYH9

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.

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 PIERCE2 family.

RefSeq proteins (1): NP_001185713* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026507	PIRC1/2	Family

Pfam: PF14892

UniProt features (5 total): sequence conflict 2, chain 1, region of interest 1, compositionally biased region 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-H3BRN8-F1	74.30	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GOZGIT_ESR1_TARGETS_DN, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_CYTOPLASMIC_MICROTUBULE, GOCC_CILIUM, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (4): cilium movement (GO:0003341), determination of left/right symmetry (GO:0007368), flagellated sperm motility (GO:0030317), axoneme assembly (GO:0035082)

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

GO Cellular Component (8): axonemal microtubule (GO:0005879), sperm flagellum (GO:0036126), axonemal A tubule inner sheath (GO:0160111), 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	3
microtubule-based movement	1
determination of bilateral symmetry	1
left/right pattern formation	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
binding	1
cytoplasmic microtubule	1
axoneme	1
9+2 motile cilium	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	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

870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIERCE2	CFAP53	Q96M91	456
PIERCE2	PIERCE1	Q5BN46	447
PIERCE2	ODAD1	Q96M63	437
PIERCE2	TEKTIP1	A6NCJ1	419
PIERCE2	PRRC2B	Q5JSZ5	400
PIERCE2	GTSF1	Q8WW33	348
PIERCE2	CFAP161	Q6P656	337
PIERCE2	CLXN	Q9HAE3	334
PIERCE2	EFHC2	Q5JST6	325
PIERCE2	ODAD4	Q96NG3	280
PIERCE2	SLCO3A1	Q9UIG8	279
PIERCE2	EFCAB6	Q5THR3	275
PIERCE2	CIMIP2B	A8MTA8	272
PIERCE2	TEKT5	Q96M29	264
PIERCE2	ODAD3	A5D8V7	262

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PIERCE2	QRICH1	psi-mi:“MI:0915”(physical association)	0.560
QRICH1	PIERCE2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): C15orf65 (Two-hybrid), C15orf65 (Cross-Linking-MS (XL-MS)), C15orf65 (Co-fractionation), C15orf65 (Co-fractionation)

ESM2 similar proteins: A0A1B0GTD5, A0A1B0GUX0, A0A3Q1LFK7, A0A3Q1MT14, A2BFC9, A4II40, A4QMS7, A6NJV1, A6NL82, A8QW39, B0BM24, B0UXH9, B5X5D0, B9EJX3, E1B9R1, E1BNS6, F1MMV1, F1P3Y5, H3BRN8, Q0VB26, Q2T9Q3, Q2TA11, Q32L72, Q32P67, Q3B820, Q3SZR5, Q4KKZ1, Q5BN45, Q5BN46, Q5M7D8, Q5M7F8, Q5NC57, Q5SPV6, Q5SVJ3, Q5VZQ5, Q6AYM0, Q6P3G4, Q6ZVS7, Q8CDT5, Q8CDU5

Diamond homologs: A0A3Q1LFK7, H3BRN8, V9GXK1, Q32P67

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2 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

317 predictions. Top by Δscore:

Variant	Effect	Δscore
15:55408785:GG:G	donor_gain	0.9900
15:55408785:GGGTG:G	donor_loss	0.9900
15:55408786:GG:G	donor_gain	0.9900
15:55408787:G:GA	donor_loss	0.9900
15:55408788:T:A	donor_loss	0.9900
15:55408787:G:GG	donor_gain	0.9800
15:55417760:G:GG	donor_gain	0.9800
15:55418218:TTTAG:T	acceptor_loss	0.9800
15:55418219:TTAG:T	acceptor_loss	0.9800
15:55418221:A:AG	acceptor_gain	0.9800
15:55418221:A:AT	acceptor_loss	0.9800
15:55418222:G:GG	acceptor_gain	0.9800
15:55408609:GA:G	donor_gain	0.9600
15:55408782:ACCGG:A	donor_gain	0.9600
15:55408784:CGG:C	donor_gain	0.9600
15:55408785:GGG:G	donor_gain	0.9600
15:55408789:GAG:G	donor_loss	0.9600
15:55418221:AG:A	acceptor_gain	0.9600
15:55418222:GG:G	acceptor_gain	0.9600
15:55417758:GT:G	donor_gain	0.9500
15:55418144:G:T	donor_gain	0.9500
15:55418222:GGATA:G	acceptor_gain	0.9500
15:55417753:GCTT:G	donor_gain	0.9400
15:55418222:GGAT:G	acceptor_gain	0.9400
15:55408610:A:G	donor_gain	0.9300
15:55408783:CCGG:C	donor_gain	0.9300
15:55410317:T:TA	donor_gain	0.8700
15:55410318:A:AA	donor_gain	0.8700
15:55418222:GGA:G	acceptor_gain	0.8700
15:55418214:A:AG	acceptor_gain	0.8200

AlphaMissense

792 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:55418310:T:C	F36L	0.982
15:55418312:T:A	F36L	0.982
15:55418312:T:G	F36L	0.982
15:55418303:T:A	N33K	0.951
15:55418303:T:G	N33K	0.951
15:55418463:T:C	F87L	0.932
15:55418465:T:A	F87L	0.932
15:55418465:T:G	F87L	0.932
15:55418513:T:A	N103K	0.905
15:55418513:T:G	N103K	0.905
15:55418308:T:A	V35E	0.904
15:55418384:A:C	K60N	0.896
15:55418384:A:T	K60N	0.896
15:55418311:T:G	F36C	0.895
15:55418313:T:C	S37P	0.895
15:55418299:G:A	G32D	0.891
15:55418379:T:G	Y59D	0.879
15:55418299:G:T	G32V	0.878
15:55418311:T:C	F36S	0.878
15:55418310:T:A	F36I	0.867
15:55418380:A:C	Y59S	0.858
15:55418310:T:G	F36V	0.854
15:55418298:G:C	G32R	0.852
15:55418386:C:T	T61I	0.849
15:55418301:A:G	N33D	0.847
15:55418316:T:C	C38R	0.831
15:55418404:G:A	G67D	0.831
15:55418427:T:C	F75L	0.829
15:55418429:T:A	F75L	0.829
15:55418429:T:G	F75L	0.829

dbSNP variants (sampled 300 via entrez): RS1000163896 (15:55412322 G>A,C), RS1000277444 (15:55406617 T>C,G), RS1000390453 (15:55417562 A>T), RS1000500363 (15:55413229 C>A,G,T), RS1000698041 (15:55413073 C>G), RS1000865735 (15:55417912 G>A), RS1000870888 (15:55408029 G>A), RS1000893135 (15:55413411 A>C), RS1000923158 (15:55408191 C>T), RS1001086245 (15:55419129 G>A), RS1001346862 (15:55413195 G>A), RS1001676718 (15:55413004 C>T), RS1001847168 (15:55418768 TAGAA>T), RS1002010654 (15:55413773 A>C), RS1002118338 (15:55418396 T>A,C)

Disease associations

OMIM: gene MIM:619669 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
mercuric bromide	decreases expression, affects cotreatment	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
perfluoro-n-nonanoic acid	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
jinfukang	decreases expression	1
Cadmium	decreases expression	1
Lipopolysaccharides	decreases expression, decreases reaction	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
S-Nitrosoglutathione	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1330	KM-H2	Cancer cell line	Male

Clinical trials (associated diseases)

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