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…

LOFmechanismARLOEUF 1.044 OMIM phenotypes

Clinical Summary— MKS1

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Gene-Disease Validity (ClinGen)

ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

189 unique Pathogenic / Likely Pathogenic· 416 VUS of 1180 total submissions

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Clinical Trials

5 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MKS1

Authoritative clinical overview · Recommended first read

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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

ClinVar Variant Classifications

1180 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69

Likely Pathogenic120

VUS416

Likely Benign470

Benign24

Conflicting72

Pathogenic

120

Likely Pathogenic

416

VUS

470

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	52	9	8	0	69
Likely Pathogenic	107	8	5	0	120
VUS	8	355	38	15	416
Likely Benign	4	18	251	197	470
Benign	0	2	22	0	24
Conflicting	—				72
Total	171	392	324	212	1,171

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap MKS1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →