ZCCHC2

Chr 18

zinc finger CCHC-type containing 2

Also known as: C18orf49

NCBI Gene: 54877 ENSG00000141664 UniProt: Q9C0B9 OMIM: 620095

The protein is predicted to bind nucleic acids, phosphatidylinositol, and zinc ions, and localizes to the cytoplasm. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. The gene shows autosomal dominant inheritance and is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.29).

OMIM ResearchSummary from RefSeq

Predicted to enable nucleic acid binding activity; phosphatidylinositol binding activity; and zinc ion binding activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

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

0.28

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.994

Z-score 5.11

OE 0.14 (0.08–0.28)

Highly constrained

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

Missense Constraint?

0.45Z-score

OE missense 0.95 (0.88–1.02)

516 obs / 545.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.08–0.28)

0≤0.351.4

Missense OE?0.95 (0.88–1.02)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 6 / 41.6Missense obs/exp: 516 / 545.4Syn Z: -1.50

Background carrier burden — how many people carry a rare variant somewhere in ZCCHC2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 25

1,839 rare PASS variants

Rare truncating (LoF)

1 in 770

156 rare PASS variants

Rare synonymous (reference)

1 in 51

846 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZCCHC2. 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 35	1 in 850
South Asian	~43k	1 in 26	1 in 1,300
Remaining (unassigned)	~30k	1 in 27	1 in 380
European (Finnish)	~27k	1 in 73	1 in 1,900
Admixed American	~22k	1 in 27	1 in 740
African / African American	~21k	1 in 27	1 in 880
East Asian	~20k	1 in 34	1 in 3,500
Ashkenazi Jewish	~13k	1 in 81	1 in 1,400
Middle Eastern	~2,884	1 in 37	1 in 240

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): 10 of 14 coding exons well covered in gnomAD exomes; exons 1, 4, 7, 10 marginal. Genomes: all 14.? see exons ↓