PIBF1

Summary

PIBF1 (progesterone immunomodulatory binding factor 1, HGNC:23352) is a protein-coding gene on chromosome 13q21.33-q22.1, encoding Progesterone-induced-blocking factor 1 (Q8WXW3). Plays a role in ciliogenesis.

This gene encodes a protein that is induced by the steroid hormone progesterone and plays a role in the maintenance of pregnancy. The encoded protein regulates multiple facets of the immune system to promote normal pregnancy including cytokine synthesis, natural killer (NK) cell activity, and arachidonic acid metabolism. Low serum levels of this protein have been associated with spontaneous pre-term labor in humans. This protein may promote the proliferation, migration and invasion of glioma.

Source: NCBI Gene 10464 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Joubert syndrome 33 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 255 total — 8 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 44
• MANE Select transcript: NM_006346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23352
Approved symbol	PIBF1
Name	progesterone immunomodulatory binding factor 1
Location	13q21.33-q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CEP90, PIBF
Ensembl gene	ENSG00000083535
Ensembl biotype	protein_coding
OMIM	607532
Entrez	10464

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000326291, ENST00000469712, ENST00000486330, ENST00000489797, ENST00000489922, ENST00000492803, ENST00000615625, ENST00000617689, ENST00000866779, ENST00000933347, ENST00000958682

RefSeq mRNA: 2 — MANE Select: NM_006346 NM_001349655, NM_006346

CCDS: CCDS31991

Canonical transcript exons

ENST00000326291 — 18 exons

Exon	Start	End
ENSE00000533122	72965274	72965404
ENSE00000802357	72835243	72835368
ENSE00000802358	72854057	72854155
ENSE00000802359	72893784	72893949
ENSE00000802360	72908531	72908681
ENSE00000802361	72917076	72917166
ENSE00001121334	72782133	72782349
ENSE00001160768	72783423	72783721
ENSE00001382240	72931165	72931267
ENSE00001474966	72827733	72827914
ENSE00001910364	73015869	73016461
ENSE00003468976	72821849	72821982
ENSE00003532868	72973591	72973675
ENSE00003535408	72797907	72798026
ENSE00003562600	72792447	72792547
ENSE00003622097	72795359	72795557
ENSE00003672959	72998822	72998995
ENSE00003675616	72827010	72827118

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 94.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8266 / max 339.4426, expressed in 1757 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135334	14.1162	1701
135335	6.1864	1535
135333	0.9910	539
135337	0.3100	170
135336	0.1537	75
135341	0.0621	12
135344	0.0071	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.44	gold quality
ventricular zone	UBERON:0003053	93.03	gold quality
sural nerve	UBERON:0015488	91.71	gold quality
left testis	UBERON:0004533	90.45	gold quality
right testis	UBERON:0004534	90.33	gold quality
bronchial epithelial cell	CL:0002328	90.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.93	gold quality
testis	UBERON:0000473	89.76	gold quality
cortical plate	UBERON:0005343	89.59	gold quality
ganglionic eminence	UBERON:0004023	89.26	gold quality
adrenal tissue	UBERON:0018303	89.02	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.12	gold quality
epithelium of bronchus	UBERON:0002031	86.89	gold quality
tendon	UBERON:0000043	86.71	gold quality
right lobe of thyroid gland	UBERON:0001119	86.43	gold quality
stromal cell of endometrium	CL:0002255	86.16	gold quality
bronchus	UBERON:0002185	86.12	gold quality
right uterine tube	UBERON:0001302	85.77	gold quality
left lobe of thyroid gland	UBERON:0001120	85.68	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.53	gold quality
cartilage tissue	UBERON:0002418	85.24	gold quality
thyroid gland	UBERON:0002046	85.18	gold quality
tibial nerve	UBERON:0001323	84.50	gold quality
lower esophagus mucosa	UBERON:0035834	84.38	gold quality
adenohypophysis	UBERON:0002196	84.17	gold quality
left ovary	UBERON:0002119	83.99	gold quality
endocervix	UBERON:0000458	83.96	gold quality
right ovary	UBERON:0002118	83.79	gold quality
islet of Langerhans	UBERON:0000006	83.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.53

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PGR

miRNA regulators (miRDB)

30 targeting PIBF1, 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-3163	100.00	77.23	8605
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-4445-5P	97.21	66.16	832
HSA-MIR-1277-3P	93.47	68.97	156

Literature-anchored findings (GeneRIF, showing 32)

• The 48-kDa N-terminal part of PIBF is biologically active, and the part of the molecule responsible for modulating natural killer cell activity is encoded by exons 2-4. (PMID:14634107)
• PIBF production is a characteristic feature of normal pregnancy, and determination of PIBF concentration in urine might be of use for the diagnosis of threatened premature pregnancy termination. (PMID:15269099)
• progesterone induced blocking factor overexpression is associated with breast neoplasms (PMID:15305375)
• PIBF phosphorylates PKC via binding to the IL-4R, without affecting intracellular Ca(++). These findings explain the mechanism by which PIBF supports a Th2 dominant cytokine pattern. (PMID:16433831)
• PIBF concentrations in urine and serum of patients with threatened abortion were significantly lower than in healthy pregnant women. (PMID:19290853)
• promotes secretion of type 2 cytkines by activated lymphocytes from pregnant woman (PMID:19371956)
• PIBF plays a role in both normal pregnancy and tumor biology. (PMID:20367622)
• CEP90 was characterized as a component of pericentriolar satellites. (PMID:21224392)
• PIBF affects the expression of leptin and its receptor, and PIBF expression is inversely related to trophoblast invasiveness. (PMID:21632119)
• increased serum levels after dydrogesterone supplementation in women with threatened preterm delivery; positive correlation with the length of gestation (PMID:22032897)
• Suggest that urinary PIBF levels may predict graft rejection in transplant recipients. (PMID:22172828)
• CEP90 physically interacts with PCM-1 at centriolar satellites, and this interaction is essential for centrosomal accumulation of the centriolar satellites and eventually for primary cilia formation. (PMID:23110211)
• Data indicate that silencing of progesterone-induced blocking factor (PIBF) increased invasiveness as well as MMP-2,-9 secretion of HTR8/SVneo trophoblast, and decreased those of HT-1080 cells. (PMID:23807209)
• decreased kisspeptin and PIBF expressions in trophoblasts and deciduas are associated with recurrent spontaneous abortion (PMID:24225150)
• reduced expression during late pregnancy and resorption (PMID:24325791)
• progesterone-induced blocking factor is intracellularly expressed by the cultured cells from Glioblastoma (PMID:24474429)
• Progesterone-induced blocking factor is hormonally regulated in human astrocytoma cells, and increases their growth through the IL-4R/JAK1/STAT6 pathway (PMID:25218441)
• Maternal serum progesterone-induced blocking factor (PIBF) in the prediction of preterm birth. (PMID:25818991)
• These data show that exposure to an allogeneic stimulus is not needed to cause a marked rise in PIBF, merely progesterone alone is sufficient. (PMID:26634256)
• this study shows that preterm birth may be predictable at 24-28 gestational week by lower than normal pregnancy PIBF values (PMID:27479613)
• blood and placental tissue level expression of PIBF is concordant and correlates with both progesterone receptor expression status as well as final pregnancy outcome (PMID:27728856)
• B cells are a significant producer of PIBF1 in human choriodecidua in late gestation. Preterm labor was associated with a lower level of active PIBF1 in late gestation choriodecidua. (PMID:27918564)
• PIBF promotes proliferation, migration, and invasion of human glioblastoma cells. (PMID:28168193)
• In conditioned media of PIBF-deficient JEG-3 cells, primary lung and ovarian cancer cells MMP9 activity was reduced. PIBF silencing resulted in increased E-cadherin expression, suggesting that by down regulating E-cadherin expression, PIBF might interfere with the cell-cell adhesion mechanisms and by increasing MMP activity induced extracellular matrix degradation, facilitates the invasion of tumor cells. (PMID:29107859)
• We found at high levels of expression of PIBF protein in epithelial ovarian cancer patients. These data demonstrate that tumor cells can secrete PIBF to escape the immune system (PMID:29962287)
• Characterisation of serum progesterone and progesterone-induced blocking factor (PIBF) levels across trimesters in healthy pregnant women. (PMID:32123187)
• PIBF1 suppresses the ATR/CHK1 signaling pathway and promotes proliferation and motility of triple-negative breast cancer cells. (PMID:32529408)
• Progesterone-induced blocking factor (PIBF) influences the expression of membrane progesterone receptors (mPRs) on peripheral CD4(+) T lymphocyte cells in normal fertile females. (PMID:33914290)
• A ciliopathy complex builds distal appendages to initiate ciliogenesis. (PMID:34241634)
• Biologia futura: embryo-maternal communication via progesterone-induced blocking factor (PIBF) positive embryo-derived extracellular vesicles. Their role in maternal immunomodulation. (PMID:34554496)
• PIBF1 regulates multiple gene expression via impeding long-range chromatin interaction to drive the malignant transformation of HPV16 integration epithelial cells. (PMID:37182685)
• PIBF1 regulates trophoblast syncytialization and promotes cardiovascular development. (PMID:38374152)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pibf1	ENSDARG00000013006
mus_musculus	Pibf1	ENSMUSG00000022064
rattus_norvegicus	Pibf1	ENSRNOG00000009208

Protein

Protein identifiers

Progesterone-induced-blocking factor 1 — Q8WXW3 (reviewed: Q8WXW3)

Alternative names: Centrosomal protein of 90 kDa

All UniProt accessions (2): Q8WXW3, A0A087WUI6

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in ciliogenesis. Pericentriolar protein required to maintain mitotic spindle pole integrity. Required for the centrosomal accumulation of PCM1 and the recruitment of centriolar satellite proteins such as BBS4. Via association with PCM1 may be involved in primary cilia formation. Required for CEP63 centrosomal localization and its interaction with WDR62. Together with CEP63 promotes centriole duplication. Promotes the centrosomal localization of CDK2. The secreted form is a mediator of progesterone that by acting on the phospholipase A2 enzyme interferes with arachidonic acid metabolism, induces a Th2 biased immune response, and by controlling decidual natural killer cells (NK) activity exerts an anti-abortive effect. Increases the production of Th2-type cytokines by signaling via the JAK/STAT pathway. Activates STAT6 and inhibits STAT4 phosphorylation. Signaling via a not identified receptor seems to implicate IL4R and a GPI-anchored protein.

Subunit / interactions. Isoform 1 interacts with PCM1, BBS4 and CEP63. Interacts with IL4R. Interacts with CFAP53.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Secreted Nucleus. Centriolar satellite. Secreted Secreted.

Tissue specificity. Expressed at highest levels in testis. Moderate expression is detected in spleen, thymus, prostate, ovary, small intestine, and colon. Expressed in the first trimester pregnancy decidua. Localized to extravillous cytotrophoblast (at protein level). Also found in syncytiotrophoblast and part of the villous cytotrophoblast. Isoform 1 is expressed in first trimester and term villous trophoblast; trophoblast cells can additionally express other isoforms. Overexpressed in solid tumors from stomach and uterus and in cells from ovary, cervical, breast, lymphoma and leukemia cancer.

Disease relevance. May be associated with microcephaly. Joubert syndrome 33 (JBTS33) [MIM:617767] A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS33 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Induction. By progesterone.

Miscellaneous. During normal pregnancy, the production is continuously increasing until the 37th gestational week and is followed by a sharp decrease after the 41st week of gestation. In pathological pregnancies, urinary levels fail to increase. Candidate for the diagnosis of threatened premature pregnancy termination.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8WXW3-1	1, 90 kDa form	yes
Q8WXW3-2	2
Q8WXW3-3	3
Q8WXW3-4	4, 34/35 kDa form

RefSeq proteins (2): NP_001336584, NP_006337* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026205	PIBF1	Family

UniProt features (19 total): sequence variant 5, region of interest 4, sequence conflict 4, splice variant 4, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXW3-F1	77.70	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 319 (showing top): chr13q21, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, MODULE_97, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_NEGATIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_CHROMOSOME_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, MODULE_182, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (13): immune system process (GO:0002376), mitotic metaphase chromosome alignment (GO:0007080), negative regulation of prostaglandin biosynthetic process (GO:0031393), negative regulation of interleukin-12 production (GO:0032695), positive regulation of interleukin-10 production (GO:0032733), negative regulation of natural killer cell activation (GO:0032815), positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531), negative regulation of tyrosine phosphorylation of STAT protein (GO:0042532), activation of Janus kinase activity (GO:0042976), cilium assembly (GO:0060271), protein localization to centrosome (GO:0071539), mitotic spindle assembly (GO:0090307), non-motile cilium assembly (GO:1905515)

GO Molecular Function (3): interleukin-4 receptor binding (GO:0005136), protein binding (GO:0005515), identical protein binding (GO:0042802)

GO Cellular Component (9): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), microtubule organizing center (GO:0005815), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), extracellular region (GO:0005576), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
mitotic sister chromatid segregation	2
tyrosine phosphorylation of STAT protein	2
regulation of tyrosine phosphorylation of STAT protein	2
microtubule organizing center	2
biological_process	1
mitotic cell cycle	1
metaphase chromosome alignment	1
mitotic cell cycle process	1
prostaglandin biosynthetic process	1
regulation of prostaglandin biosynthetic process	1
negative regulation of fatty acid biosynthetic process	1
negative regulation of cytokine production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
positive regulation of cytokine production	1
interleukin-10 production	1
regulation of interleukin-10 production	1
natural killer cell activation	1
regulation of natural killer cell activation	1
negative regulation of lymphocyte activation	1
positive regulation of peptidyl-tyrosine phosphorylation	1
negative regulation of receptor signaling pathway via JAK-STAT	1
negative regulation of peptidyl-tyrosine phosphorylation	1
peptidyl-tyrosine phosphorylation	1
activation of protein kinase activity	1
positive regulation of receptor signaling pathway via JAK-STAT	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
protein localization to microtubule organizing center	1
mitotic spindle organization	1
spindle assembly	1
mitotic nuclear division	1
cilium assembly	1

Protein interactions and networks

STRING

1304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIBF1	LGALS1	P09382	712
PIBF1	CEP20	Q96NB1	665
PIBF1	MZT1	Q08AG7	603
PIBF1	BORA	Q6PGQ7	602
PIBF1	CCDC138	Q96M89	590
PIBF1	PGR	P06401	550
PIBF1	CEP72	Q9P209	530
PIBF1	CEP131	Q9UPN4	524
PIBF1	KIAA0753	Q2KHM9	514
PIBF1	PRF1	P14222	509
PIBF1	DIS3	Q9Y2L1	507
PIBF1	TBC1D31	Q96DN5	504
PIBF1	CCDC61	Q9Y6R9	498
PIBF1	CCDC13	Q8IYE1	497
PIBF1	IL10	P22301	494

IntAct

130 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
EXOC3	EXOC5	psi-mi:“MI:0914”(association)	0.790
PIBF1	CEP63	psi-mi:“MI:0915”(physical association)	0.760
PCM1	PIBF1	psi-mi:“MI:0915”(physical association)	0.720
PIBF1	PCM1	psi-mi:“MI:0914”(association)	0.720
PIBF1	PCM1	psi-mi:“MI:0915”(physical association)	0.720
CIT	TAX1BP3	psi-mi:“MI:0914”(association)	0.690
PCM1	KIAA0753	psi-mi:“MI:0914”(association)	0.650
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
PIBF1	CEP131	psi-mi:“MI:0915”(physical association)	0.530
SLC25A41	NUDT19	psi-mi:“MI:0914”(association)	0.530
BORCS6	HSBP1	psi-mi:“MI:0914”(association)	0.530
VAT1L	PIBF1	psi-mi:“MI:0914”(association)	0.530
CPNE2	HIP1	psi-mi:“MI:0914”(association)	0.530
KIAA0753	OFD1	psi-mi:“MI:2364”(proximity)	0.480
ODF2	PLK1	psi-mi:“MI:0914”(association)	0.480
CCDC13	CEP290	psi-mi:“MI:0914”(association)	0.460
CEP162	CCP110	psi-mi:“MI:2364”(proximity)	0.420
PIBF1	IL4R	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (272): PIBF1 (Affinity Capture-RNA), PIBF1 (Affinity Capture-RNA), PIBF1 (Affinity Capture-MS), PIBF1 (Affinity Capture-MS), PIBF1 (Affinity Capture-MS), PIBF1 (Affinity Capture-MS), PIBF1 (Proximity Label-MS), PIBF1 (Proximity Label-MS), PIBF1 (Proximity Label-MS), PIBF1 (Proximity Label-MS), PIBF1 (Affinity Capture-MS), PIBF1 (Affinity Capture-MS), PIBF1 (Affinity Capture-MS), PIBF1 (Proximity Label-MS), PIBF1 (Proximity Label-MS)

ESM2 similar proteins: A0A8M2BID5, A0A8M9PQ61, A1Z8P9, A6QR54, B4KE73, E9Q7G0, F1R4Y7, O15083, O55156, O60437, O61308, Q11102, Q13439, Q15643, Q3SWS9, Q5DTN8, Q5M9N0, Q5PQ23, Q5RI56, Q5U4E6, Q5VZ66, Q5ZKK5, Q66H89, Q6DFL0, Q6PH08, Q6ZU80, Q7ZW57, Q811U3, Q8BI22, Q8BVL9, Q8CDI6, Q8CDI7, Q8CGB3, Q8HYY4, Q8IUD2, Q8K3M6, Q8WXW3, Q91VW5, Q96AA8, Q96N16

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 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
Loss of Nlp from mitotic centrosomes	15	31.7×	4e-17
Loss of proteins required for interphase microtubule organization from the centrosome	15	31.7×	4e-17
AURKA Activation by TPX2	15	30.4×	6e-17
Recruitment of mitotic centrosome proteins and complexes	15	27.2×	3e-16
Anchoring of the basal body to the plasma membrane	18	27.1×	6e-19
Regulation of PLK1 Activity at G2/M Transition	16	27.1×	4e-17
Recruitment of NuMA to mitotic centrosomes	15	23.3×	3e-15
Centrosome maturation	6	20.3×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	6	39.6×	3e-06
protein localization to centrosome	5	30.4×	1e-04
non-motile cilium assembly	7	18.3×	3e-05
positive regulation of transcription elongation by RNA polymerase II	5	13.6×	3e-03
mitotic cytokinesis	5	11.7×	6e-03
cilium assembly	14	9.3×	3e-07
intracellular protein localization	9	8.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	9
Uncertain significance	135
Likely benign	47
Benign	15

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1979240	NM_006346.4(PIBF1):c.118C>T (p.Arg40Ter)	Pathogenic
2920180	NM_006346.4(PIBF1):c.157C>T (p.Arg53Ter)	Pathogenic
4082120	NM_006346.4(PIBF1):c.1939del (p.Ile647fs)	Pathogenic
446198	NM_006346.4(PIBF1):c.1910A>C (p.Asp637Ala)	Pathogenic
446200	NM_006346.4:c.(672+1_673-1)_(1322+1_1323-1)del	Pathogenic
599034	NM_006346.4(PIBF1):c.1453C>T (p.Gln485Ter)	Pathogenic
807653	NM_006346.4(PIBF1):c.1801C>T (p.Arg601Ter)	Pathogenic
981932	NM_006346.4(PIBF1):c.1181_1182insGCTTCGCAGATTGAAAACCAACCAAGAAATTGATCA (p.Arg385_Arg396dup)	Pathogenic
1324895	NM_006346.4(PIBF1):c.1213C>T (p.Arg405Ter)	Likely pathogenic
1332798	NM_006346.4(PIBF1):c.1150_1151insCAGATTGAAAACCAACCAAGAAATTGATCAGCTTCG (p.Ile384delinsThrAspTer)	Likely pathogenic
1687224	NM_006346.4(PIBF1):c.597_598insAAGAAAGGAATCCATTAAGAAAG (p.Glu200delinsLysLysGlyIleHisTer)	Likely pathogenic
217688	NM_006346.4(PIBF1):c.1669del (p.Leu557fs)	Likely pathogenic
2412732	NM_006346.4(PIBF1):c.1056_1068del (p.Lys353fs)	Likely pathogenic
2691411	NM_006346.4(PIBF1):c.1731-1G>A	Likely pathogenic
3030435	NM_006346.4(PIBF1):c.802_803del (p.Lys268fs)	Likely pathogenic
3338618	NM_006346.4(PIBF1):c.2076_2100del (p.Val693fs)	Likely pathogenic
598934	NM_006346.4(PIBF1):c.1508A>G (p.Tyr503Cys)	Likely pathogenic

SpliceAI

3453 predictions. Top by Δscore:

Variant	Effect	Δscore
13:72792441:A:AG	acceptor_gain	1.0000
13:72792441:AC:A	acceptor_gain	1.0000
13:72792442:C:A	acceptor_gain	1.0000
13:72792442:C:G	acceptor_gain	1.0000
13:72792445:A:AG	acceptor_gain	1.0000
13:72792446:G:GG	acceptor_gain	1.0000
13:72792446:GA:G	acceptor_gain	1.0000
13:72792446:GAT:G	acceptor_gain	1.0000
13:72792446:GATT:G	acceptor_gain	1.0000
13:72792543:GCCAG:G	donor_gain	1.0000
13:72792544:CCAG:C	donor_gain	1.0000
13:72792545:CAG:C	donor_gain	1.0000
13:72792546:AG:A	donor_gain	1.0000
13:72792546:AGGT:A	donor_loss	1.0000
13:72792547:GG:G	donor_gain	1.0000
13:72792548:G:GG	donor_gain	1.0000
13:72792548:GTAA:G	donor_loss	1.0000
13:72795352:A:AG	acceptor_gain	1.0000
13:72795352:AAT:A	acceptor_gain	1.0000
13:72795353:A:G	acceptor_gain	1.0000
13:72795354:TGTA:T	acceptor_loss	1.0000
13:72795355:GTAGC:G	acceptor_loss	1.0000
13:72795357:A:AG	acceptor_gain	1.0000
13:72795357:AGC:A	acceptor_loss	1.0000
13:72795358:G:GC	acceptor_gain	1.0000
13:72795358:GC:G	acceptor_gain	1.0000
13:72795358:GCA:G	acceptor_gain	1.0000
13:72795358:GCAA:G	acceptor_gain	1.0000
13:72795358:GCAAA:G	acceptor_gain	1.0000
13:72795553:TATCT:T	donor_gain	1.0000

AlphaMissense

5003 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:72835359:G:C	R405P	0.997
13:72854062:T:C	L410P	0.997
13:72854082:G:C	A417P	0.997
13:72835329:T:C	L395P	0.996
13:72792469:T:C	L92P	0.995
13:72795418:T:C	L138P	0.995
13:72795439:T:C	L145P	0.995
13:72827015:G:C	R271P	0.995
13:72827785:T:C	L323P	0.995
13:72854065:G:C	R411P	0.995
13:72908652:T:C	L537P	0.995
13:72795409:A:C	Q135P	0.994
13:72835275:T:C	L377P	0.994
13:72917157:T:C	L574P	0.994
13:72783669:T:C	L67P	0.993
13:72827764:T:C	L316P	0.993
13:72908556:T:C	L505P	0.993
13:72917165:A:C	S577R	0.993
13:72931165:T:A	S577R	0.993
13:72931165:T:G	S577R	0.993
13:72931175:G:C	A581P	0.993
13:72854070:G:C	A413P	0.992
13:72908640:T:C	L533P	0.992
13:72973659:T:C	L678P	0.992
13:72854103:G:C	A424P	0.991
13:72893903:T:C	L481P	0.991
13:72917154:G:C	R573P	0.991
13:72931167:T:A	V578D	0.991
13:72827791:G:C	R325P	0.990
13:72827860:T:C	L348P	0.990

dbSNP variants (sampled 300 via entrez): RS1000005998 (13:72982486 C>T), RS1000019577 (13:72977273 C>T), RS1000022856 (13:72808333 G>T), RS1000037698 (13:72830746 G>A), RS1000038321 (13:72801843 G>A), RS1000043500 (13:72869624 AT>A), RS1000046053 (13:72942760 G>A), RS1000052045 (13:72846170 C>G), RS1000069100 (13:72790202 T>C), RS1000095321 (13:72869776 C>A), RS1000108081 (13:72849367 A>G), RS1000144500 (13:72930882 A>G), RS1000146643 (13:72989071 A>C), RS1000151574 (13:72890712 A>G), RS1000152357 (13:72802174 G>C)

Disease associations

OMIM: gene MIM:607532 | disease phenotypes: MIM:617767, MIM:213300, MIM:143890, MIM:209920, MIM:220200

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 33	Definitive	Autosomal recessive
Joubert syndrome	Supportive	Autosomal recessive

Mondo (6): Joubert syndrome 33 (MONDO:0033311), Joubert syndrome (MONDO:0018772), familial hypercholesterolemia (MONDO:0005439), MHC class II deficiency 1 (MONDO:0971005), Dandy-Walker syndrome (MONDO:0009072), cephalocele (MONDO:0017078)

Orphanet (3): Isolated Joubert syndrome (Orphanet:475), Isolated Dandy-Walker malformation (Orphanet:217), Cephalocele (Orphanet:268817)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000202	Orofacial cleft
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000548	Cone/cone-rod dystrophy
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000657	Oculomotor apraxia
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0001159	Syndactyly
HP:0001161	Hand polydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001320	Cerebellar vermis hypoplasia
HP:0001337	Tremor
HP:0001696	Situs inversus totalis
HP:0001744	Splenomegaly
HP:0001829	Foot polydactyly
HP:0002084	Encephalocele
HP:0002104	Apnea

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002250_10	Blood pressure measurement (low sodium intervention)	2.000000e-09
GCST004630_192	Mean corpuscular hemoglobin	6.000000e-11
GCST005038_83	Allergic disease (asthma, hay fever or eczema)	3.000000e-08
GCST008151_6	Waist circumference	6.000000e-06
GCST008160_51	Waist circumference	6.000000e-06
GCST010277_13	Gout	3.000000e-08
GCST90002390_543	Mean corpuscular hemoglobin	2.000000e-20
GCST90002392_412	Mean corpuscular volume	2.000000e-23
GCST90002397_62	Mean spheric corpuscular volume	3.000000e-20
GCST90002403_519	Red blood cell count	5.000000e-12
GCST90002404_376	Red cell distribution width	2.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005402	response to low sodium diet
EFO:0006335	systolic blood pressure
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003616	Dandy-Walker Syndrome	C10.228.140.252.300; C10.228.140.602.500; C10.500.205; C16.131.666.205

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Dydrogesterone	affects expression, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
MT19c compound	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Progesterone	increases expression	1
Mifepristone	decreases expression	1
Aflatoxin M1	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00655265	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	PHASE4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	PHASE4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	PHASE4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT00355615	PHASE3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	PHASE3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	PHASE3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	PHASE3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	PHASE3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT01813006	PHASE3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT01841684	PHASE3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02624869	PHASE3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	PHASE3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	PHASE3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
NCT04798430	PHASE3	ENROLLING_BY_INVITATION	Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction
NCT05142722	PHASE3	COMPLETED	Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT05238519	PHASE3	ACTIVE_NOT_RECRUITING	Improved Diagnosis of Familial Hypercholesterolemia Across the Northland (ID-FH)
NCT05425745	PHASE3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05952856	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids
NCT05952869	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)
NCT06005597	PHASE3	COMPLETED	Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT00079846	PHASE2	TERMINATED	Implitapide in Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00079859	PHASE2	TERMINATED	Implitapide in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00477594	PHASE2	COMPLETED	Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
NCT00751608	PHASE2	WITHDRAWN	Effect of APL180 on Endothelial Function in Familial Hypercholesterolemia Patients
NCT02597127	PHASE2	COMPLETED	Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol (LDL-C)
NCT03060577	PHASE2	COMPLETED	An Extension Trial of Inclisiran in Participants With Cardiovascular Disease and High Cholesterol
NCT04455581	PHASE2	UNKNOWN	A Study to Determine the Safety, Tolerability, and Efficacy of SHR-1209 in Patients With Familial Hypercholesterolemia
NCT04941599	PHASE2	RECRUITING	2-Hydroxybenzylamine (2-HOBA) to Reduce HDL Modification and Improve HDL Function in Familial Hypercholesterolemia (FH)
NCT05261126	PHASE2	COMPLETED	A Study of the Efficacy and Safety of Enclitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)
NCT00004809	PHASE1	COMPLETED	Phase I Study of Ex Vivo Liver-Directed Gene Therapy for Familial Hypercholesterolemia
NCT02709850	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia
NCT03747224	PHASE1	COMPLETED	Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients
NCT05043181	PHASE1	NOT_YET_RECRUITING	Exosome-based Nanoplatform for Ldlr mRNA Delivery in FH
NCT05851066	PHASE1	COMPLETED	A VSA003 Phase 1 Study in Chinese Adult Healthy Volunteers
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)