PAGR1

Chr 16

PAXIP1 associated glutamate rich protein 1

Also known as: C16orf53, GAS, PA1

NCBI Gene: 79447 ENSG00000280789 UniProt: Q9BTK6 OMIM: 612033

PAGR1 encodes a transcriptional cofactor that associates with histone methyltransferase complexes and regulates estrogen receptor signaling and cell cycle progression. Mutations cause autosomal dominant neurodevelopmental disorder with developmental delay, intellectual disability, and behavioral abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.538), consistent with its role in essential cellular processes.

OMIM ResearchSummary from RefSeq, UniProt

Enables nuclear estrogen receptor binding activity. Involved in positive regulation of cell cycle G1/S phase transition; positive regulation of intracellular estrogen receptor signaling pathway; and positive regulation of transcription by RNA polymerase II. Located in nucleus. Part of MLL3/4 complex. Biomarker of esophagus squamous cell carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.54

Clinical Summary— PAGR1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.74) — some intolerance to loss-of-function variants.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 38 VUS of 49 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.54LOEUF

pLI 0.743

Z-score 2.44

OE 0.11 (0.04–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.63Z-score

OE missense 0.86 (0.74–0.99)

129 obs / 150.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.54)

0≤0.351.4

Missense OE?0.86 (0.74–0.99)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 8.8Missense obs/exp: 129 / 150.9Syn Z: -0.32

ClinVar Variant Classifications

49 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS38

Likely Benign3

Benign1

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	1	0	0	0	1
VUS	0	38	0	0	38
Likely Benign	0	3	0	0	3
Benign	0	0	1	0	1
Conflicting	—				1
Total	1	41	2	0	45

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

View in ClinVar →

135 pathogenic / likely-pathogenic (of 151) ClinVar copy-number / structural variants overlap PAGR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →