NBEAL1

Chr 2

neurobeachin like 1

Also known as: A530083I02Rik, ALS2CR16, ALS2CR17

NCBI Gene: 65065 ENSG00000144426 UniProt: Q6ZS30 OMIM: 609816

The NBEAL1 protein binds to protein kinases and is involved in protein localization within the cytosol and membrane compartments. Mutations cause autosomal recessive developmental delays, intellectual disability, and seizures with onset typically in early childhood. This gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq

Predicted to enable protein kinase binding activity. Predicted to be involved in protein localization. Predicted to be active in cytosol and membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.65

Clinical Summary— NBEAL1

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Population Constraint (gnomAD)

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

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ClinVar Variants

336 VUS of 406 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.000

Z-score 5.07

OE 0.54 (0.45–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.88Z-score

OE missense 0.85 (0.81–0.90)

1068 obs / 1255.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.45–0.65)

0≤0.351.4

Missense OE?0.85 (0.81–0.90)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 77 / 142.3Missense obs/exp: 1068 / 1255.1Syn Z: 1.82

ClinVar Variant Classifications

406 submitted variants in ClinVar

ClinVar

Classification Summary

VUS336

Likely Benign21

Benign8

Conflicting1

336

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	335	0	0	336
Likely Benign	1	12	0	8	21
Benign	0	3	2	3	8
Conflicting	—				1
Total	2	350	2	11	366

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap NBEAL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →