PIBF1

progesterone immunomodulatory binding factor 1

Basic information

Region (hg38): 13:72782133-73016461

Previous symbols: [ "C13orf24" ]

Links

ENSG00000083535 ∙ NCBI:10464 ∙ OMIM:607532 ∙ HGNC:23352 ∙ Uniprot:Q8WXW3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ciliopathy (Moderate), mode of inheritance: AR
• Joubert syndrome 33 (Strong), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome 33 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 33	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic; Renal	26167768; 29695797; 30858804

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PIBF1 gene.

• Inborn_genetic_diseases (114 variants)
• not_provided (81 variants)
• Joubert_syndrome_33 (27 variants)
• PIBF1-related_disorder (22 variants)
• not_specified (3 variants)
• Joubert_syndrome (3 variants)
• Cephalocele (2 variants)
• Dandy-Walker_syndrome (2 variants)
• Familial_hypercholesterolemia (1 variants)
• MHC_class_II_deficiency_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIBF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006346.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	29	2	32
missense	1	4	126	15	3	149
nonsense	4	3	3			10
start loss						0
frameshift	1	7	2			10
splice donor/acceptor (+/-2bp)		1	7			8
Total	6	15	139	44	5

Highest pathogenic variant AF is 0.00009961184

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIBF1	protein_coding	protein_coding	ENST00000326291	17	234395

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125637	0	103	125740	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.456	392	367	1.07	0.0000193	4961
Missense in Polyphen		168	162.08	1.0365		2238
Synonymous	-0.813	138	126	1.09	0.00000605	1305
Loss of Function	3.16	26	50.2	0.518	0.00000313	597

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00131	0.00122
Ashkenazi Jewish	0.00	0.00
East Asian	0.000406	0.000381
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000508	0.000484
Middle Eastern	0.000406	0.000381
South Asian	0.000551	0.000490
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in ciliogenesis. {ECO:0000269|PubMed:26167768}.; FUNCTION: Isoform 4: 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 naturakl killer cells (NK) activity exerts an anti-abortive effect (PubMed:14634107, PubMed:3863495, PubMed:12516630). 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 (PubMed:16393965, PubMed:25218441). {ECO:0000269|PubMed:12516630, ECO:0000269|PubMed:14634107, ECO:0000269|PubMed:16393965, ECO:0000269|PubMed:25218441, ECO:0000269|PubMed:3863495, ECO:0000305|PubMed:11407300}.
• Disease: DISEASE: Note=May be associated with microcephaly. {ECO:0000305|PubMed:26297806}.; DISEASE: 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. {ECO:0000269|PubMed:26167768}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0850

Intolerance Scores

• loftool: 0.941
• rvis_EVS: 0.43
• rvis_percentile_EVS: 77.29

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.549

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: immune system process;mitotic metaphase plate congression;negative regulation of prostaglandin biosynthetic process;negative regulation of interleukin-12 production;positive regulation of interleukin-10 production;negative regulation of natural killer cell activation;positive regulation of tyrosine phosphorylation of STAT protein;negative regulation of tyrosine phosphorylation of STAT protein;activation of Janus kinase activity;cilium assembly;protein localization to centrosome;mitotic spindle assembly;non-motile cilium assembly
• Cellular component: extracellular space;nucleus;centrosome;microtubule organizing center;centriolar satellite
• Molecular function: interleukin-4 receptor binding;protein binding