NUPR1

Chr 16

nuclear protein 1, transcriptional regulator

Also known as: COM1, P8

NCBI Gene: 26471 ENSG00000176046 UniProt: O60356

The protein encoded by this gene is a transcription regulator that converts cellular stress signals into gene expression programs, controlling cell cycle progression, apoptosis, autophagy, and DNA repair responses. Mutations in NUPR1 cause autosomal recessive neurodevelopmental disorder with microcephaly and structural brain anomalies, typically presenting in early infancy with developmental delays and neurological features. The gene shows tolerance to loss-of-function variants (pLI 0.004, LOEUF 1.91), consistent with the recessive inheritance pattern observed in affected patients.

ResearchSummary from RefSeq, UniProt

Enables DNA binding activity and transcription coactivator activity. Involved in several processes, including negative regulation of autophagosome assembly; negative regulation of programmed cell death; and regulation of generation of precursor metabolites and energy. Acts upstream of or within negative regulation of cell cycle. Located in nucleoplasm and perinuclear region of cytoplasm. Part of protein-DNA complex. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.91

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.91LOEUF

pLI 0.004

Z-score -0.41

OE 1.29 (0.52–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.12Z-score

OE missense 1.04 (0.86–1.27)

68 obs / 65.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.29 (0.52–1.91)

0≤0.351.4

Missense OE?1.04 (0.86–1.27)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 3 / 2.3Missense obs/exp: 68 / 65.3Syn Z: 0.02

Background carrier burden — how many people carry a rare variant somewhere in NUPR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 280

123 rare PASS variants

Rare truncating (LoF)

1 in 2,000

20 rare PASS variants

Rare synonymous (reference)

1 in 1,800

45 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NUPR1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 460	1 in 1,900
South Asian	~43k	1 in 250	1 in 7,200
Remaining (unassigned)	~30k	1 in 460	1 in 5,000
European (Finnish)	~27k	1 in 450	1 in 3,800
Admixed American	~22k	1 in 220	1 in 2,700
African / African American	~21k	1 in 220	≈ 1 in 17,000
East Asian	~20k	1 in 360	≈ 1 in 6,600
Ashkenazi Jewish	~13k	≈ 1 in 4,400	none seen
Middle Eastern	~2,884	1 in 360	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓