CLNS1A

Chr 11

chloride nucleotide-sensitive channel 1A

Also known as: CLCI, CLNS1B, ICln

NCBI Gene: 1207 ENSG00000074201 UniProt: P54105

This gene encodes a protein that functions in multiple regulatory pathways. The encoded protein complexes with numerous cytosolic proteins and performs diverse functions including regulation of small nuclear ribonucleoprotein biosynthesis, platelet activation and cytoskeletal organization. The protein is also found associated with the plasma membrane where it functions as a chloride current regulator. Pseudogenes of this gene are found on chromosomes 1, 4 and 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

Research

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

—

P/LP missense

0.72

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.081

Z-score 2.27

OE 0.31 (0.15–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.88Z-score

OE missense 0.78 (0.66–0.92)

96 obs / 123.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.15–0.72)

0≤0.351.4

Missense OE?0.78 (0.66–0.92)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 4 / 12.7Missense obs/exp: 96 / 123.6Syn Z: 0.72

Background carrier burden — how many people carry a rare variant somewhere in CLNS1A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 390

262 rare PASS variants

Rare truncating (LoF)

1 in 3,500

44 rare PASS variants

Rare synonymous (reference)

1 in 540

106 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLNS1A. 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 460	1 in 3,600
South Asian	~43k	1 in 250	1 in 1,700
Remaining (unassigned)	~30k	1 in 230	1 in 4,300
European (Finnish)	~27k	1 in 380	1 in 2,900
Admixed American	~22k	1 in 400	1 in 2,800
African / African American	~21k	1 in 330	≈ 1 in 5,400
East Asian	~20k	1 in 240	1 in 1,500
Ashkenazi Jewish	~13k	1 in 500	none seen
Middle Eastern	~2,884	1 in 410	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): 5 of 6 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 6.? see exons ↓