NALF1

Chr 13

NALCN channel auxiliary factor 1

Also known as: FAM155A, NLF-1, NLF1

NCBI Gene: 728215 ENSG00000204442 UniProt: B1AL88 OMIM: 619899

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to contribute to stretch-activated, monoatomic cation-selective, calcium channel activity. Involved in regulation of neuronal action potential and sodium ion transmembrane transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.31

LOEUF· LoF intol.

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Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.976

Z-score 3.76

OE 0.10 (0.04–0.31)

Highly constrained

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

Missense Constraint?

0.31Z-score

OE missense 0.94 (0.85–1.05)

233 obs / 246.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.31)

0≤0.351.4

Missense OE?0.94 (0.85–1.05)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 2 / 20.3Missense obs/exp: 233 / 246.6Syn Z: -0.17

Background carrier burden — how many people carry a rare variant somewhere in NALF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

556 rare PASS variants

Rare truncating (LoF)

1 in 5,400

30 rare PASS variants

Rare synonymous (reference)

1 in 140

278 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NALF1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 10,000
South Asian	~43k	1 in 140	1 in 3,100
Remaining (unassigned)	~30k	1 in 150	1 in 2,700
European (Finnish)	~27k	1 in 440	1 in 570
Admixed American	~22k	1 in 140	1 in 4,400
African / African American	~21k	1 in 94	1 in 2,800
East Asian	~20k	1 in 130	1 in 3,900
Ashkenazi Jewish	~13k	1 in 310	none seen
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓