ZCCHC7

Chr 9

zinc finger CCHC-type containing 7

Also known as: AIR1, HSPC086

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
DNmechanismLOEUF 0.91
Clinical SummaryZCCHC7
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
72 unique Pathogenic / Likely Pathogenic· 73 VUS of 169 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.91LOEUF
pLI 0.000
Z-score 1.93
OE 0.61 (0.420.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.35Z-score
OE missense 0.94 (0.851.04)
273 obs / 289.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.420.91)
00.351.4
Missense OE0.94 (0.851.04)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 18 / 29.3Missense obs/exp: 273 / 289.7Syn Z: 0.79
DN
0.6648th %ile
GOF
0.5268th %ile
LOF
0.3357th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

169 submitted variants in ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic9
VUS73
Likely Benign7
63
Pathogenic
9
Likely Pathogenic
73
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
63
0
63
Likely Pathogenic
0
0
9
0
9
VUS
0
68
5
0
73
Likely Benign
0
6
0
1
7
Benign
0
0
0
0
0
Total074771152

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ZCCHC7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC