ING1

Chr 13

inhibitor of growth family member 1

Also known as: p24ING1c, p33, p33ING1, p33ING1b, p47, p47ING1a

NCBI Gene: 3621 ENSG00000153487 UniProt: Q9UK53 OMIM: 601566

The ING1 protein is a nuclear tumor suppressor that cooperates with p53 in regulating cell growth by modulating p53-dependent transcriptional activation. Mutations cause squamous cell carcinoma of the head and neck, which occurs somatically rather than being inherited. The gene is not highly constrained against loss-of-function variants, consistent with its role in somatic rather than germline disease.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a tumor suppressor protein that can induce cell growth arrest and apoptosis. The encoded protein is a nuclear protein that physically interacts with the tumor suppressor protein TP53 and is a component of the p53 signaling pathway. Reduced expression and rearrangement of this gene have been detected in various cancers. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Squamous cell carcinoma, head and neck, somaticMIM #275355

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Squamous cell carcinoma, head and neck, somatic; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.010

Z-score 2.26

OE 0.38 (0.21–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.49Z-score

OE missense 0.92 (0.83–1.02)

255 obs / 278.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.21–0.76)

0≤0.351.4

Missense OE?0.92 (0.83–1.02)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 6 / 15.7Missense obs/exp: 255 / 278.1Syn Z: -0.13

Background carrier burden — how many people carry a rare variant somewhere in ING1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

625 rare PASS variants

Rare truncating (LoF)

1 in 510

93 rare PASS variants

Rare synonymous (reference)

1 in 120

359 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ING1. 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 130	1 in 500
South Asian	~43k	1 in 75	1 in 320
Remaining (unassigned)	~30k	1 in 100	1 in 600
European (Finnish)	~27k	1 in 200	1 in 1,700
Admixed American	~22k	1 in 97	1 in 550
African / African American	~21k	1 in 120	1 in 330
East Asian	~20k	1 in 92	1 in 3,900
Ashkenazi Jewish	~13k	1 in 490	none seen
Middle Eastern	~2,884	1 in 150	1 in 270

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 ↓