MKS1

Chr 17AR

MKS transition zone complex subunit 1

Also known as: BBS13, JBTS28, MES, MKS, POC12

NCBI Gene: 54903ENSG00000011143UniProt: Q9NXB0

The protein encoded by this gene localizes to the basal body and is required for formation of the primary cilium in ciliated epithelial cells. Mutations in this gene result in Meckel syndrome type 1 and in Bardet-Biedl syndrome type 13. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Bardet-Biedl syndrome 13MIM #615990
AR
Joubert syndrome 28MIM #617121
AR
Meckel syndrome 1MIM #249000
AR
Meckel syndrome 1MIM #249000
AR
1187
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
5
Active trials
Clinical Summary— MKS1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
1187 total variants — no pathogenic classifications of 1187 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

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.
1.04LOEUF
pLI 0.000
Z-score 1.35
OE 0.76 (0.57–1.04)
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.
0.49Z-score
OE missense 0.92 (0.84–1.02)
296 obs / 320.8 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.0.76 (0.57–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.84–1.02)
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.0.99
0≤1.21.6
LoF obs/exp: 29 / 37.9Missense obs/exp: 296 / 320.8Syn Z: 0.06

ClinVar Variant Classifications

1187 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

MKS1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MKS1-related Bardet-Biedl syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

Bardet-Biedl syndrome 13

MIM #615990

Molecular basis of disorder known

Autosomal recessive

Joubert syndrome 28

MIM #617121

Molecular basis of disorder known

Autosomal recessive

Meckel syndrome 1

MIM #249000

Molecular basis of disorder known

Autosomal recessive

Meckel syndrome 1

MIM #249000

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Case Report: Preimplantation Genetic Testing for Meckel Syndrome Induced by Novel Compound Heterozygous Mutations of MKS1.
Lin T et al.·Front Genet
2022🔓 Open AccessCase report
Regulation of canonical Wnt signalling by the ciliopathy protein MKS1 and the E2 ubiquitin-conjugating enzyme UBE2E1.
Szymanska K et al.·Elife
2022🔓 Open Access
Mild Clinical Presentation of Joubert Syndrome in a Male Adult Carrying Biallelic MKS1 Truncating Variants.
Brunetti-Pierri R et al.·Diagnostics (Basel)
2021🔓 Open Access
Novel Compound Heterozygous Variants in MKS1 Leading to Joubert Syndrome.
Luo M et al.·Front Genet
2020🔓 Open Access
Formation of the B9-domain protein complex MKS1-B9D2-B9D1 is essential as a diffusion barrier for ciliary membrane proteins.
Okazaki M et al.·Mol Biol Cell
2020🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Hepato/Renal Fibrocystic DiseaseAutosomal Recessive Polycystic Kidney DiseaseJoubert Syndrome

ARPKD Database Study

RECRUITING
NCT01401998Children's Hospital of PhiladelphiaStarted 2011-06
Leber Congenital Amaurosis 10BlindnessLeber Congenital Amaurosis

A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)

ACTIVE NOT RECRUITING
NCT03913143Phase PHASE2, PHASE3ProQR TherapeuticsStarted 2019-04-04
sepofarsenSham
Leber Congenital Amaurosis 10BlindnessLeber Congenital Amaurosis

Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)

RECRUITING
NCT06891443Phase PHASE3Laboratoires TheaStarted 2025-06-04
sepofarsenPlacebo IVT
Retinitis PigmentosaLeber Congenital Amaurosis

Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis

ACTIVE NOT RECRUITING
NCT05203939Phase PHASE1, PHASE2OcugenStarted 2022-01-24
OCU400 Low DoseOCU400 Med DoseOCU400 High Dose
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation

External Resources

Links to major genomics databases and tools