ZNF721

Chr 4

zinc finger protein 721

NCBI Gene: 170960 ENSG00000182903 UniProt: Q8TF20

The protein is a zinc finger transcription factor that regulates gene expression by RNA polymerase II through DNA binding in the nucleus. Mutations in ZNF721 cause autosomal dominant neurodevelopmental disorder with intellectual disability, though the gene shows relatively low constraint to loss-of-function variation. The disorder primarily affects the central nervous system with developmental delays and cognitive impairment.

ResearchSummary from RefSeq, UniProt

Predicted to enable transcription cis-regulatory region binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nuclear lumen. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.89

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.095

Z-score 0.06

OE 0.93 (0.26–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.77Z-score

OE missense 1.23 (1.15–1.32)

578 obs / 469.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.93 (0.26–1.89)

0≤0.351.4

Missense OE?1.23 (1.15–1.32)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 1 / 1.1Missense obs/exp: 578 / 469.9Syn Z: -2.41

Background carrier burden — how many people carry a rare variant somewhere in ZNF721?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 36

1,364 rare PASS variants

Rare truncating (LoF)

1 in 300

213 rare PASS variants

Rare synonymous (reference)

1 in 88

490 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF721. 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 45	1 in 260
South Asian	~43k	1 in 42	1 in 160
Remaining (unassigned)	~30k	1 in 32	1 in 250
European (Finnish)	~27k	1 in 130	1 in 600
Admixed American	~22k	1 in 35	1 in 250
African / African American	~21k	1 in 33	1 in 330
East Asian	~20k	1 in 37	1 in 88
Ashkenazi Jewish	~13k	1 in 130	1 in 1,700
Middle Eastern	~2,884	1 in 37	1 in 180

Each group is summed over the variants that are rare in that group. 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 ↓