CLTRN

Chr X

collectrin, amino acid transport regulator

Also known as: NX-17, NX17, TMEM27

NCBI Gene: 57393 ENSG00000147003 UniProt: Q9HBJ8 OMIM: 300631

The encoded protein traffics amino acid transporters to the apical brush border of proximal tubules and regulates SNARE complex formation in pancreatic beta cells for insulin exocytosis. Mutations cause Hartnup disorder, an autosomal recessive condition affecting neutral amino acid transport in the kidneys and intestines. The gene shows low constraint to loss-of-function variation, consistent with the relatively mild phenotype of Hartnup disorder.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a type 1 transmembrane protein that is important for trafficking amino acid transporters to the apical brush border of proximal tubules. The encoded protein binds to amino acid transporters and regulates their expression on the plasma membrane. It also plays a role in controlling insulin exocytosis by regulating formation of the SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor) complex in pancreatic beta cells. The extracellular domain of the encoded protein may be cleaved and shed from the plasma membrane specifically in pancreatic beta cells. [provided by RefSeq, Jun 2013]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.75

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.75LOEUF

pLI 0.000

Z-score 0.09

OE 0.96 (0.52–1.75)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.28Z-score

OE missense 1.09 (0.91–1.31)

81 obs / 74.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.96 (0.52–1.75)

0≤0.351.4

Missense OE?1.09 (0.91–1.31)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 6 / 6.2Missense obs/exp: 81 / 74.2Syn Z: 0.82

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 580

173 rare PASS variants

Rare truncating (LoF)

1 in 5,600

30 rare PASS variants

Rare synonymous (reference)

1 in 1,200

61 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLTRN. 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)	~561k	1 in 800	1 in 8,600
South Asian	~36k	1 in 320	1 in 4,800
Remaining (unassigned)	~31k	1 in 580	1 in 6,000
European (Finnish)	~27k	1 in 960	none seen
Admixed American	~23k	1 in 640	1 in 650
African / African American	~21k	1 in 320	1 in 2,500
East Asian	~20k	1 in 830	1 in 3,300
Ashkenazi Jewish	~13k	none seen	≈ 1 in 13,000
Middle Eastern	~2,757	1 in 340	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 6 marginal. Genomes: all 6.? see exons ↓