FXYD2

Chr 11

FXYD domain containing ion transport regulator 2

Also known as: ATP1G1, HOMG2

NCBI Gene: 486 ENSG00000137731 UniProt: P54710

This gene encodes a member of the FXYD family of transmembrane proteins. This particular protein encodes the sodium/potassium-transporting ATPase subunit gamma. Mutations in this gene have been associated with Renal Hypomagnesemia-2. Alternatively spliced transcript variants have been described. Read-through transcripts have been observed between this locus and the upstream FXYD domain-containing ion transport regulator 6 (FXYD6, GeneID 53826) locus.[provided by RefSeq, Feb 2011]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHypomagnesemia 2

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · renal hypomagnesemia 2 · AD · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.20

LOEUF

Multiple*

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?

1.20LOEUF

pLI 0.114

Z-score 1.30

OE 0.38 (0.16–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.16Z-score

OE missense 1.06 (0.85–1.35)

49 obs / 46.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.38 (0.16–1.20)

0≤0.351.4

Missense OE?1.06 (0.85–1.35)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 2 / 5.2Missense obs/exp: 49 / 46.0Syn Z: -0.98

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 330

101 rare PASS variants

Rare truncating (LoF)

1 in 3,500

24 rare PASS variants

Rare synonymous (reference)

1 in 180

45 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for 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 350	1 in 3,200
South Asian	~43k	1 in 340	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 300	1 in 3,300
European (Finnish)	~27k	1 in 1,100	none seen
Admixed American	~22k	1 in 340	1 in 2,200
African / African American	~21k	1 in 380	1 in 1,100
East Asian	~20k	1 in 490	1 in 3,000
Ashkenazi Jewish	~13k	≈ 1 in 4,300	none seen
Middle Eastern	~2,884	1 in 360	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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓