KCNJ13

Chr 2ARAD

potassium inwardly rectifying channel subfamily J member 13

Also known as: KIR1.4, KIR7.1, LCA16, SVD

This gene encodes an inwardly rectifying potassium channel that allows potassium ions to flow into cells, with characteristically low conductance and minimal sensitivity to typical channel blockers. Mutations cause Leber congenital amaurosis 16 and snowflake vitreoretinal degeneration, both affecting retinal function and vision. The gene shows both autosomal recessive and autosomal dominant inheritance patterns depending on the specific condition.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Leber congenital amaurosis 16MIM #614186
AR
Snowflake vitreoretinal degenerationMIM #193230
AD
0
Active trials
10
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.86
LOEUF
LOF*
Mechanism· G2P
Clinical SummaryKCNJ13
🧬
Gene-Disease Validity (ClinGen)
inherited retinal dystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📖
GeneReview available — KCNJ13
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.014
Z-score 1.92
OE 0.41 (0.210.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.93Z-score
OE missense 0.62 (0.530.71)
123 obs / 199.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.210.86)
00.351.4
Missense OE0.62 (0.530.71)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 5 / 12.2Missense obs/exp: 123 / 199.9Syn Z: 0.91
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveKCNJ13-related snowflake vitreoretinal degenerationOTHERAD
definitiveKCNJ13-related Leber congenital amaurosisLOFAR
DN
0.76top 25%
GOF
0.82top 10%
LOF
0.2093th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNHowever, unlike wildtype KCNJ13, KCNJ13 with the R162W mutation did not develop whole cell currents when expressed in Xenopus oocytes. Coinjection experiments revealed a dominant-negative effect of mutant KCNJ13 on currents produced by wildtype KCNJ13.PMID:23255580

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KCNJ13 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC