ZNG1A

Chr 9

Zn regulated GTPase metalloprotein activator 1A

Also known as: CBWD1, COBP

NCBI Gene: 55871 ENSG00000172785 UniProt: Q9BRT8

Predicted to enable GTPase activity and zinc chaperone activity. Involved in kidney development. Predicted to be located in nucleus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Active trials

Pathogenic / LP

112

ClinVar variants

Pubs (1 yr)

-2.0

Missense Z

1.20

LOEUF

Clinical Summary— ZNG1A

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

13 Pathogenic / Likely Pathogenic· 85 VUS of 112 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.20LOEUF

pLI 0.000

Z-score 1.00

OE 0.72 (0.45–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

-2.00Z-score

OE missense 1.48 (1.32–1.66)

206 obs / 139.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.72 (0.45–1.20)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.48 (1.32–1.66)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15

0≤1.21.6

LoF obs/exp: 11 / 15.2Missense obs/exp: 206 / 139.6Syn Z: -0.87

0.74top 25%

GOF

0.6247th %ile

LOF

0.2777th %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.