ZCCHC7

Chr 9

zinc finger CCHC-type containing 7

Also known as: AIR1, HSPC086

NCBI Gene: 84186 ENSG00000147905 UniProt: Q8N3Z6

This gene encodes an RNA-binding protein involved in nuclear RNA surveillance and is located in the cytosol and nucleolus. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. The gene shows minimal constraint against loss-of-function variants based on population genetics data.

ResearchSummary from RefSeq

Enables RNA binding activity. Predicted to be involved in nuclear RNA surveillance. Located in cytosol and nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.91

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.000

Z-score 1.93

OE 0.61 (0.42–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.35Z-score

OE missense 0.94 (0.85–1.04)

273 obs / 289.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.42–0.91)

0≤0.351.4

Missense OE?0.94 (0.85–1.04)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 18 / 29.3Missense obs/exp: 273 / 289.7Syn Z: 0.79

Background carrier burden — how many people carry a rare variant somewhere in ZCCHC7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 95

613 rare PASS variants

Rare truncating (LoF)

1 in 980

118 rare PASS variants

Rare synonymous (reference)

1 in 170

235 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZCCHC7. 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 160	1 in 1,300
South Asian	~43k	1 in 68	1 in 840
Remaining (unassigned)	~30k	1 in 93	1 in 1,100
European (Finnish)	~27k	1 in 370	1 in 760
Admixed American	~22k	1 in 85	1 in 520
African / African American	~21k	1 in 61	1 in 1,200
East Asian	~20k	1 in 100	1 in 690
Ashkenazi Jewish	~13k	1 in 760	1 in 2,100
Middle Eastern	~2,884	1 in 63	≈ 1 in 2,800

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): 7 of 8 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 8.? see exons ↓