FXYD6

Chr 11

FXYD domain containing ion transport regulator 6

NCBI Gene: 53826 ENSG00000137726 UniProt: Q9H0Q3 OMIM: 606683

This gene encodes a member of the FXYD family of transmembrane proteins. This particular protein encodes phosphohippolin, which likely affects the activity of Na,K-ATPase. Multiple alternatively spliced transcript variants encoding the same protein have been described. Related pseudogenes have been identified on chromosomes 10 and X. Read-through transcripts have been observed between this locus and the downstream sodium/potassium-transporting ATPase subunit gamma (FXYD2, GeneID 486) locus.[provided by RefSeq, Feb 2011]

OMIM Research

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

—

P/LP missense

0.65

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.65LOEUF

pLI 0.619

Z-score 2.16

OE 0.14 (0.05–0.65)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.78Z-score

OE missense 0.70 (0.53–0.92)

36 obs / 51.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.05–0.65)

0≤0.351.4

Missense OE?0.70 (0.53–0.92)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 1 / 7.3Missense obs/exp: 36 / 51.7Syn Z: -0.60

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 550

160 rare PASS variants

Rare truncating (LoF)

1 in 9,500

26 rare PASS variants

Rare synonymous (reference)

1 in 810

54 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FXYD6. 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 640	1 in 6,600
South Asian	~43k	1 in 300	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 540	≈ 1 in 15,000
European (Finnish)	~27k	1 in 690	none seen
Admixed American	~22k	1 in 430	≈ 1 in 4,600
African / African American	~21k	1 in 280	≈ 1 in 17,000
East Asian	~20k	1 in 200	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 4,300	none seen
Middle Eastern	~2,884	≈ 1 in 580	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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓