KIAA0586

Chr 14AR

KIAA0586

Also known as: JBTS23, SRTD14, Talpid3

NCBI Gene: 9786ENSG00000100578UniProt: Q9BVV6

This gene encodes a conserved centrosomal protein that functions in ciliogenesis and responds to hedgehog signaling. Mutations in this gene causes Joubert syndrome 23. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Aug 2016]

Primary Disease Associations & Inheritance

Joubert syndrome 23MIM #616490
AR
Short-rib thoracic dysplasia 14 with polydactylyMIM #616546
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— KIAA0586
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.72LOEUF
pLI 0.000
Z-score 3.44
OE 0.54 (0.42–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.37Z-score
OE missense 0.96 (0.91–1.02)
735 obs / 763.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.54 (0.42–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.91–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 36 / 66.2Missense obs/exp: 735 / 763.9Syn Z: -0.03

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

KIAA0586 · protein map & ClinVar variants

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

Gene2Phenotype Curations

KIAA0586-related Joubert syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
KIAA0586 GENE; KIAA0586
MIM #610178 · *

Joubert syndrome 23

MIM #616490

Molecular basis of disorder known

Autosomal recessive

Short-rib thoracic dysplasia 14 with polydactyly

MIM #616546

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — KIAA0586
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome.
Aksu Uzunhan T et al.·Clin Neurol Neurosurg
2023
Expanding the Phenotypic Spectrum of Pathogenic KIAA0586 Variants: From Joubert Syndrome to Hydrolethalus Syndrome.
Deconte D et al.·Int J Mol Sci
2024Case report
Prenatal Diagnosis of Joubert Syndrome 23 With Left Isomerism: A Novel Phenotype Associated With Pathogenic KIAA0586 Variant.
Casteleyn T et al.·Prenat Diagn
2025Case report
A novel 1.38-kb deletion combined with a single nucleotide variant in KIAA0586 as a cause of Joubert syndrome.
Shen Y et al.·BMC Med Genomics
2023Case report
Compound heterozygous splicing variants in KIAA0586 cause fetal short-rib thoracic dysplasia and cerebellar malformation: Use of exome sequencing in prenatal diagnosis.
Zhao Q et al.·Mol Genet Genomic Med
2023
The splice c.1815G>A variant in KIAA0586 results in a phenotype bridging short-rib-polydactyly and oral-facial-digital syndrome: A case report and literature review.
Cocciadiferro D et al.·Medicine (Baltimore)
2020Case report
Homozygosity for the c.428delG variant in KIAA0586 in a healthy individual: implications for molecular testing in patients with Joubert syndrome.
Pauli S et al.·J Med Genet
2019Case report
The genetic spectrum of congenital ocular motor apraxia type Cogan: an observational study, continued.
Schröder S et al.·Orphanet J Rare Dis
2023
Prospective Evaluation of Kidney Disease in Joubert Syndrome.
Fleming LR et al.·Clin J Am Soc Nephrol
2017
Pathogenic cryptic variants detectable through exome data reanalysis significantly increase the diagnostic yield in Joubert syndrome.
D'Abrusco F et al.·Eur J Hum Genet
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools