NBPF12
Chr 1NBPF member 12
Also known as: COAS1, KIAA1245
The NBPF12 protein contains tandemly repeated DUF1220 domains and is part of the neuroblastoma breakpoint gene family that has undergone extensive duplication in humans. Copy number variations in the chromosomal region containing NBPF genes have been associated with multiple neurodevelopmental conditions including microcephaly, macrocephaly, autism, schizophrenia, and cognitive disability, as well as congenital heart disease and kidney anomalies. This gene shows extremely low constraint against loss-of-function variants, suggesting tolerance to complete gene loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
234 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 192 |
Likely Pathogenic | — | — | — | — | 25 |
VUS | — | — | — | — | 6 |
Likely Benign | — | — | — | — | 6 |
Benign | — | — | — | — | 1 |
Conflicting | — | 1 | |||
| Total | — | 231 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NBPF12 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →No open access results found
External Resources
Links to major genomics databases and tools