PIBF1

Chr 13AR

progesterone immunomodulatory binding factor 1

Also known as: C13orf24, CEP90, JBTS33, PIBF

NCBI Gene: 10464 ENSG00000083535 UniProt: Q8WXW3 OMIM: 607532

This protein is induced by progesterone and plays a role in ciliogenesis. Mutations cause Joubert syndrome 33, a ciliopathy presenting in infancy with cerebellar vermis hypoplasia, developmental delay, hypotonia, and characteristic breathing abnormalities. The condition follows autosomal recessive inheritance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.721 OMIM phenotype

Clinical Summary— PIBF1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

19 unique Pathogenic / Likely Pathogenic· 133 VUS of 254 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PIBF1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.000

Z-score 3.16

OE 0.52 (0.38–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.46Z-score

OE missense 1.07 (0.98–1.16)

392 obs / 367.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.52 (0.38–0.72)

0≤0.351.4

Missense OE?1.07 (0.98–1.16)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 26 / 50.2Missense obs/exp: 392 / 367.4Syn Z: -0.81

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePIBF1-related Joubert syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.79top 25%

GOF

0.6834th %ile

LOF

0.2777th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

254 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic11

VUS133

Likely Benign52

Benign14

Conflicting9

Pathogenic

Likely Pathogenic

133

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	2	1	0	8
Likely Pathogenic	9	2	0	0	11
VUS	5	123	3	2	133
Likely Benign	0	12	11	29	52
Benign	0	4	7	3	14
Conflicting	—				9
Total	19	143	22	34	227

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

68 pathogenic / likely-pathogenic (of 87) ClinVar copy-number / structural variants overlap PIBF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →