MKS1

Chr 17AR

MKS transition zone complex subunit 1

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

NCBI Gene: 54903 ENSG00000011143 UniProt: Q9NXB0 OMIM: 609883

The protein localizes to the basal body and transition zone of primary cilia, where it forms part of the tectonic-like complex that regulates ciliary structure and prevents diffusion of transmembrane proteins between cilia and plasma membranes. Mutations cause autosomal recessive ciliopathies including Meckel syndrome (typically lethal with occipital encephalocele, cystic kidneys, and polydactyly), Bardet-Biedl syndrome (characterized by retinal dystrophy, obesity, polydactyly, and intellectual disability), and Joubert syndrome (featuring cerebellar vermis hypoplasia and developmental delay). This gene is not highly constrained against loss-of-function variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bardet-Biedl syndrome 13MIM #615990

Joubert syndrome 28MIM #617121

Meckel syndrome 1MIM #249000

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · ciliopathy · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.04

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — MKS1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.49Z-score

OE missense 0.92 (0.84–1.02)

296 obs / 320.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.57–1.04)

0≤0.351.4

Missense OE?0.92 (0.84–1.02)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 29 / 37.9Missense obs/exp: 296 / 320.8Syn Z: 0.06

Background carrier burden — how many people carry a rare variant somewhere in MKS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

899 rare PASS variants

Rare truncating (LoF)

1 in 550

163 rare PASS variants

Rare synonymous (reference)

1 in 160

284 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MKS1. 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 71	1 in 900
South Asian	~43k	1 in 46	1 in 310
Remaining (unassigned)	~30k	1 in 46	1 in 430
European (Finnish)	~27k	1 in 140	1 in 1,900
Admixed American	~22k	1 in 50	1 in 640
African / African American	~21k	1 in 38	1 in 880
East Asian	~20k	1 in 87	1 in 570
Ashkenazi Jewish	~13k	1 in 91	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 47	≈ 1 in 720

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