NALF1

Chr 13

NALCN channel auxiliary factor 1

Also known as: FAM155A, NLF-1, NLF1

NALF1 encodes an auxiliary component of the NALCN sodium channel complex that regulates resting membrane potential and controls neuronal excitability. Mutations cause neurodevelopmental disorders with intellectual disability, hypotonia, and seizures, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.31), indicating that complete loss of function is likely not tolerated.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
116
P/LP submissions
0%
P/LP missense
0.31
LOEUF· LoF intol.
Mechanism
Clinical SummaryNALF1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
116 unique Pathogenic / Likely Pathogenic· 64 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.976
Z-score 3.76
OE 0.10 (0.040.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.31Z-score
OE missense 0.94 (0.851.05)
233 obs / 246.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.040.31)
00.351.4
Missense OE0.94 (0.851.05)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 2 / 20.3Missense obs/exp: 233 / 246.6Syn Z: -0.17

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic116
VUS64
Likely Benign9
Benign3
116
Pathogenic
64
VUS
9
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
116
0
116
Likely Pathogenic
0
0
0
0
0
VUS
0
52
12
0
64
Likely Benign
0
2
6
1
9
Benign
0
0
3
0
3
Total0541371192

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

View in ClinVar →

Protein Context — Lollipop Plot

NALF1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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