ZSCAN2

Chr 15

zinc finger and SCAN domain containing 2

Also known as: ZFP29, ZNF854

NCBI Gene: 54993 ENSG00000176371 UniProt: Q7Z7L9

ZSCAN2 encodes a zinc finger transcription factor that regulates gene expression during spermatogenesis, particularly in post-meiotic stages of sperm development. Mutations cause autosomal recessive intellectual disability with developmental delay. The gene is highly constrained against loss-of-function variants (pLI essentially 0), indicating that complete loss of function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene contains several copies of zinc finger motif, which is commonly found in transcriptional regulatory proteins. Studies in mice show that this gene is expressed during embryonic development, and specifically in the testis in adult mice, suggesting that it may play a role in regulating genes in germ cells. Alternative splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

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?

0.80LOEUF

pLI 0.000

Z-score 2.28

OE 0.48 (0.30–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.10Z-score

OE missense 1.02 (0.93–1.11)

361 obs / 355.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.48 (0.30–0.80)

0≤0.351.4

Missense OE?1.02 (0.93–1.11)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 11 / 22.7Missense obs/exp: 361 / 355.6Syn Z: -1.84

Background carrier burden — how many people carry a rare variant somewhere in ZSCAN2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 59

907 rare PASS variants

Rare truncating (LoF)

1 in 960

92 rare PASS variants

Rare synonymous (reference)

1 in 75

353 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZSCAN2. 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 62	1 in 1,800
South Asian	~43k	1 in 59	1 in 2,300
Remaining (unassigned)	~30k	1 in 65	1 in 1,700
European (Finnish)	~27k	1 in 370	1 in 2,000
Admixed American	~22k	1 in 77	1 in 800
African / African American	~21k	1 in 57	1 in 1,300
East Asian	~20k	1 in 62	1 in 3,100
Ashkenazi Jewish	~13k	1 in 450	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 120	≈ 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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓