ZKSCAN2

Chr 16

zinc finger with KRAB and SCAN domains 2

Also known as: ZNF694

NCBI Gene: 342357 ENSG00000155592 UniProt: Q63HK3

The protein functions as a DNA-binding transcription factor that regulates gene expression by RNA polymerase II in the nucleus. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.55), indicating intolerance to protein-disrupting mutations.

ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.55

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.55LOEUF

pLI 0.000

Z-score 3.92

OE 0.36 (0.24–0.55)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.25Z-score

OE missense 0.97 (0.90–1.04)

528 obs / 544.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.24–0.55)

0≤0.351.4

Missense OE?0.97 (0.90–1.04)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 16 / 44.1Missense obs/exp: 528 / 544.3Syn Z: -0.90

Background carrier burden — how many people carry a rare variant somewhere in ZKSCAN2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 37

1,250 rare PASS variants

Rare truncating (LoF)

1 in 1,600

128 rare PASS variants

Rare synonymous (reference)

1 in 130

456 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZKSCAN2. 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 44	1 in 1,900
South Asian	~43k	1 in 34	1 in 980
Remaining (unassigned)	~30k	1 in 34	1 in 3,800
European (Finnish)	~27k	1 in 110	1 in 1,800
Admixed American	~22k	1 in 42	1 in 2,200
African / African American	~21k	1 in 25	1 in 960
East Asian	~20k	1 in 50	1 in 850
Ashkenazi Jewish	~13k	1 in 110	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 39	≈ 1 in 1,400

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 ↓