PIBF1

protein-coding

progesterone immunomodulatory binding factor 1

Gene summary

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. [provided by RefSeq, Mar 2017]

Previous symbols:

C13orf24

MANE transcript

NM_006346.4

Inheritance

ClinVar variants

P:28U:144B:52

Top phenotype

Joubert syndrome 33

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr13:72,782,133-73,016,461

External References & Databases

Ensembl (ENSG00000083535)

Transcript & Mutation Effects

hg38 • Region Span ~234.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Joubert syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018772

Submitter: Orphanet

Joubert syndrome 33DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0033311

Submitter: G2P

Joubert syndrome 33STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033311

Submitter: PanelApp Australia

Joubert syndrome 33STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033311

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Joubert syndrome 33AR

Manifestation: Craniofacial; Neurologic; Renal

Intervention: General

Rationale: 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

Refs: 26167768; 29695797; 30858804

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PIBF1 variants in ClinVar

11 Conditions Cataloged

Inborn genetic diseasesTotal: 117

not providedTotal: 90

PIBF1-related disorderTotal: 31

Joubert syndrome 33Total: 30

not specifiedTotal: 12

Joubert syndromeTotal: 3

CephaloceleTotal: 2

Dandy-Walker syndromeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006346.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	31 clinvar	3 clinvar	37
missense		4 clinvar	129 clinvar	15 clinvar	3 clinvar	151
nonsense	4 clinvar	6 clinvar	3 clinvar			13
start loss						0
frameshift	1 clinvar	11 clinvar	3 clinvar			15
splice donor/acceptor (+/-2bp)		2 clinvar	6 clinvar			8
Total	5	23	144	46	6	224

Highest pathogenic variant AF is 0.00009961184

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006346.4	RefSeq	NP_006337.2	17	MANE Select
ENST00000326291.11	Ensembl	ENSP00000317144.6	17	MANE Select
NM_001349655.2	RefSeq	NP_001336584.1	18	Standard
ENST00000615625.1	Ensembl	ENSP00000483286.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

Molecular Function

interleukin-4 receptor binding
protein binding

Cellular Component

extracellular space
nucleus
centrosome
microtubule organizing center
centriolar satellite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000326291
Coding exons: 17
Length: 234395
Individuals with no LoFs: 125637
Homozygous LoFs: 0
Heterozygous LoFs: 103
Defined: 125740
p: 0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.456	392	367	1.07	0.0000193	4961
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00089	0.00080	rare
Latino/Admixed American	0.00042	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00041	0.00038	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00051	0.00048	rare
South Asian	0.00055	0.00049	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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 (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.549

Gene Damage Prediction

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