NAB1

Chr 2

NGFI-A binding protein 1

NCBI Gene: 4664 ENSG00000138386 UniProt: Q13506 OMIM: 600800

NAB1 encodes a transcriptional repressor that inhibits the zinc finger transcription factors EGR1 and EGR2, which are important for nervous system development. Mutations cause autosomal dominant or recessive neurodevelopmental disorders with intellectual disability, developmental delay, and various neurological features. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.59), consistent with its role in essential developmental processes.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of DNA-templated transcription. Predicted to act upstream of or within endochondral ossification; nervous system development; and regulation of epidermis development. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.59

Clinical Summary— NAB1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

51 VUS of 63 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.022

Z-score 3.00

OE 0.31 (0.18–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.35Z-score

OE missense 0.76 (0.68–0.86)

194 obs / 254.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.18–0.59)

0≤0.351.4

Missense OE?0.76 (0.68–0.86)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 7 / 22.3Missense obs/exp: 194 / 254.6Syn Z: 0.45

ClinVar Variant Classifications

63 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	51	0	51
Likely Benign	1	1	2
Benign	0	0	0
Total	52	1	53

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap NAB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →