FXYD6-FXYD2

Chr 11

FXYD6-FXYD2 readthrough

This locus represents naturally occurring read-through transcription between the neighboring FXYD domain-containing ion transport regulator 6 (GeneID 53826) and sodium/potassium-transporting ATPase subunit gamma (GeneID 486) genes on chromosome 11. One read-through transcript produces a fusion protein that shares sequence identity with each individual gene product, while another read-through transcript encodes a protein that has a distinct C-terminus and only shares sequence identity with the upstream locus (GeneID 53826). [provided by RefSeq, Aug 2011]

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

0.45

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.850

Z-score 2.73

OE 0.09 (0.03–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.27Z-score

OE missense 0.90 (0.72–1.13)

54 obs / 59.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.45)

0≤0.351.4

Missense OE?0.90 (0.72–1.13)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 1 / 10.6Missense obs/exp: 54 / 59.9Syn Z: -0.01

Background carrier burden — how many people carry a rare variant somewhere in FXYD6-FXYD2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

243 rare PASS variants

Rare truncating (LoF)

1 in 3,100

38 rare PASS variants

Rare synonymous (reference)

1 in 180

66 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FXYD6-FXYD2. 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 250	1 in 2,600
South Asian	~43k	1 in 150	≈ 1 in 10,000
Remaining (unassigned)	~30k	1 in 220	1 in 2,700
European (Finnish)	~27k	1 in 480	none seen
Admixed American	~22k	1 in 220	1 in 2,800
African / African American	~21k	1 in 190	1 in 1,300
East Asian	~20k	1 in 210	none seen
Ashkenazi Jewish	~13k	1 in 2,600	none seen
Middle Eastern	~2,884	1 in 180	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 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓