KIAA0753

Chr 17AR

KIAA0753

Also known as: JBTS38, MNR, OFIP, SRTD21

NCBI Gene: 9851ENSG00000198920UniProt: Q2KHM9

This gene encodes a subunit of a protein complex that regulates ciliogenesis and cilia maintenance. The encoded protein has also been shown to regulate centriolar duplication. Mutations in this gene cause an orofaciodigital syndrome and a form of Joubert syndrome in human patients. [provided by RefSeq, May 2017]

Primary Disease Associations & Inheritance

?Joubert syndrome 38MIM #619476
AR
?Orofaciodigital syndrome XVMIM #617127
AR
Short-rib thoracic dysplasia 21 without polydactylyMIM #619479
AR
482
ClinVar variants
63
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— KIAA0753
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
63 Pathogenic / Likely Pathogenic· 203 VUS of 482 total submissions

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.
1.10LOEUF
pLI 0.000
Z-score 0.91
OE 0.87 (0.69–1.10)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.21Z-score
OE missense 0.97 (0.91–1.05)
517 obs / 530.4 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.0.87 (0.69–1.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.91–1.05)
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.0.94
0≤1.21.6
LoF obs/exp: 47 / 54.3Missense obs/exp: 517 / 530.4Syn Z: 0.67

ClinVar Variant Classifications

482 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic18
VUS203
Likely Benign160
Benign47
Conflicting9
45
Pathogenic
18
Likely Pathogenic
203
VUS
160
Likely Benign
47
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
2
30
0
45
Likely Pathogenic
10
1
7
0
18
VUS
1
190
11
1
203
Likely Benign
0
9
63
88
160
Benign
0
11
29
7
47
Conflicting
—9
Total2421314096482

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KIAA0753 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
KIAA0753 GENE; KIAA0753
MIM #617112 · *

?Joubert syndrome 38

MIM #619476

Molecular basis of disorder known

Autosomal recessive

?Orofaciodigital syndrome XV

MIM #617127

Molecular basis of disorder known

Autosomal recessive

Short-rib thoracic dysplasia 21 without polydactyly

MIM #619479

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic and phenotypic heterogeneity in KIAA0753-related ciliopathies.
Inskeep KA et al.·Am J Med Genet A
2022Case report
KIAA0753-related skeletal ciliopathy: a ninth case, extending the phenotype and reporting a novel variant.
Sabir AH et al.·Clin Dysmorphol
2021Case report
OFIP/KIAA0753 forms a complex with OFD1 and FOR20 at pericentriolar satellites and centrosomes and is mutated in one individual with oral-facial-digital syndrome.
Chevrier V et al.·Hum Mol Genet
2016Case report
Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes.
Bruel AL et al.·J Med Genet
2017Review
A new case of KIAA0753-related variant of Jeune asphyxiating thoracic dystrophy.
Faudi E et al.·Eur J Med Genet
2020Case report
Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies.
Hammarsjö A et al.·Sci Rep
2017
Mutations in KIAA0753 cause Joubert syndrome associated with growth hormone deficiency.
Stephen J et al.·Hum Genet
2017Case report
Molecular genetic findings and clinical correlations in 100 patients with Joubert syndrome and related disorders prospectively evaluated at a single center.
Vilboux T et al.·Genet Med
2017Cohort
High diagnostic yield in skeletal ciliopathies using massively parallel genome sequencing, structural variant screening and RNA analyses.
Hammarsjö A et al.·J Hum Genet
2021
Molecular diagnosis in a cohort of 114 patients with rare skeletal dysplasias.
Silveira KC et al.·Am J Med Genet C Semin Med Genet
2021Case report
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