ZNF496

Chr 1

zinc finger protein 496

Also known as: NIZP1, ZFP496, ZKSCAN17, ZSCAN49

NCBI Gene: 84838 ENSG00000162714 UniProt: Q96IT1 OMIM: 613911

This gene encodes a DNA-binding transcription factor that functions as both a transcriptional activator and repressor. ZNF496 is highly constrained against loss-of-function variants (pLI=1.00, LOEUF=0.25), suggesting that mutations likely cause severe developmental disorders, though specific associated diseases have not yet been established in the literature.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Predicted to be involved in positive regulation of DNA-templated transcription and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be located in nuclear body. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.25LOEUF

pLI 0.996

Z-score 4.29

OE 0.08 (0.03–0.25)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.40Z-score

OE missense 0.80 (0.73–0.88)

314 obs / 391.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.25)

0≤0.351.4

Missense OE?0.80 (0.73–0.88)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 2 / 25.3Missense obs/exp: 314 / 391.7Syn Z: -0.59

Background carrier burden — how many people carry a rare variant somewhere in ZNF496?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 71

742 rare PASS variants

Rare truncating (LoF)

1 in 4,900

27 rare PASS variants

Rare synonymous (reference)

1 in 150

368 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNF496. 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 86	1 in 5,400
South Asian	~43k	1 in 50	1 in 2,000
Remaining (unassigned)	~30k	1 in 60	≈ 1 in 7,300
European (Finnish)	~27k	1 in 150	none seen
Admixed American	~22k	1 in 100	≈ 1 in 22,000
African / African American	~21k	1 in 63	≈ 1 in 6,100
East Asian	~20k	1 in 78	none seen
Ashkenazi Jewish	~13k	1 in 310	none seen
Middle Eastern	~2,884	1 in 74	≈ 1 in 2,900

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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓