KCNJ16

Chr 17AR

potassium inwardly rectifying channel subfamily J member 16

Also known as: BIR9, HKTD, KIR5.1

NCBI Gene: 3773 ENSG00000153822 UniProt: Q9NPI9 OMIM: 605722

The protein encodes an inward-rectifier potassium channel that mediates basolateral potassium recycling in kidney distal tubules, which is critical for sodium reabsorption and regulation of fluid and pH balance. Mutations cause EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) with autosomal recessive inheritance. This gene is not highly constrained against loss-of-function variants, and the syndrome typically presents in infancy with seizures and progressive neurological features alongside renal salt wasting.

OMIM ResearchSummary from RefSeq, UniProt

Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which tends to allow potassium to flow into rather than out of a cell, can form heterodimers with two other inward-rectifier type potassium channels. It may function in fluid and pH balance regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hypokalemic tubulopathy and deafnessMIM #619406

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · hypokalemic alkalosis, familial, with specific renal tubulopathy · AR · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.67

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.67LOEUF

pLI 0.000

Z-score -0.41

OE 1.12 (0.76–1.67)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.00Z-score

OE missense 1.00 (0.90–1.11)

238 obs / 237.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.12 (0.76–1.67)

0≤0.351.4

Missense OE?1.00 (0.90–1.11)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 16 / 14.3Missense obs/exp: 238 / 237.9Syn Z: -0.12

Background carrier burden — how many people carry a rare variant somewhere in KCNJ16?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 90

564 rare PASS variants

Rare truncating (LoF)

1 in 870

68 rare PASS variants

Rare synonymous (reference)

1 in 140

188 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KCNJ16. 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 110	1 in 940
South Asian	~43k	1 in 60	1 in 510
Remaining (unassigned)	~30k	1 in 73	1 in 1,300
European (Finnish)	~27k	1 in 410	1 in 990
Admixed American	~22k	1 in 80	1 in 390
African / African American	~21k	1 in 88	1 in 520
East Asian	~20k	1 in 87	1 in 1,000
Ashkenazi Jewish	~13k	1 in 180	none seen
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,900

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 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓