OBSL1

Chr 2AR

obscurin like cytoskeletal adaptor 1

NCBI Gene: 23363 ENSG00000124006 UniProt: O75147 OMIM: 610991

This gene encodes a cytoskeletal adaptor protein that functions as a core component of the 3M complex, which regulates microtubule dynamics and acts as a regulator of ubiquitin ligase pathways controlling Golgi morphogenesis and dendrite patterning in the brain. Biallelic mutations cause 3-M syndrome type 2, a growth disorder characterized by severe pre- and postnatal growth restriction with distinctive facial features, inherited in an autosomal recessive pattern. The gene shows very low constraint against loss-of-function variants in the general population.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Cytoskeletal adaptor proteins function in linking the internal cytoskeleton of cells to the cell membrane. This gene encodes a cytoskeletal adaptor protein, which is a member of the Unc-89/obscurin family. The protein contains multiple N- and C-terminal immunoglobulin (Ig)-like domains and a central fibronectin type 3 domain. Mutations in this gene cause 3M syndrome type 2. Alternatively spliced transcript variants encoding different isoforms have been found in this gene. [provided by RefSeq, Mar 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

3-M syndrome 2MIM #612921

UniProt3M syndrome 2

Clinical highlights

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

0.88

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — OBSL1

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?

0.88LOEUF

pLI 0.000

Z-score 2.42

OE 0.70 (0.55–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.01Z-score

OE missense 1.00 (0.95–1.05)

1170 obs / 1170.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.55–0.88)

0≤0.351.4

Missense OE?1.00 (0.95–1.05)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 51 / 73.4Missense obs/exp: 1170 / 1170.7Syn Z: -0.19

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

OBSL1 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — OBSL1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Study on pathogenic genes of dwarfism disease by next-generation sequencing

Yang LL et al.·World J Clin Cases

2021

3M syndrome patient with a novel mutation: A case report

Luo MR et al.·World J Clin Cases

2024Case report

Chinese patients with 3M syndrome: clinical manifestations and two novel pathogenic variants

Xu N et al.·Front Genet

2023Cohort

Carrier-Free Nanovaccine: An Innovative Strategy for Ultrahigh Melanoma Neoantigen Loading.

Zeng T et al.·ACS Nano

2023

Clinical and molecular spectrum along with genotype-phenotype correlation of 25 patients diagnosed with 3 M syndrome: a study from Turkey.

Akalın A et al.·Eur J Pediatr

2024Cohort

Top 5 full-text resultsSearch PubTator3 ↗

Key Publications

Landmark & review papers · by relevance

PubMed

3M syndrome: A Tunisian seven-cases series.

Khachnaoui-Zaafrane K et al.·Eur J Med Genet

2022Case report

Three M syndrome 2 in two Indian patients.

Jacob P et al.·Am J Med Genet A

2021Case report

A rare cause of syndromic short stature: 3M syndrome in three families.

Isik E et al.·Am J Med Genet A

2021

Further expanding the mutational spectrum and investigation of genotype-phenotype correlation in 3M syndrome.

Simsek-Kiper PO et al.·Am J Med Genet A

2019

Genotype-phenotype correlations of Berardinelli-Seip congenital lipodystrophy and novel candidate genes prediction.

Ren M et al.·Orphanet J Rare Dis

2020

Top 5 results · since 2015Search PubMed ↗

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

Combined Loss of Obsc and Obsl1 in Murine Hearts Results in Diastolic Dysfunction, Altered Metabolism, and Deregulated Mitophagy.

Fujita K et al.·Circ Heart Fail

2025

Novel OBSL1 Variant in a Chinese Patient with 3M Syndrome: The c.458dupG Mutation May Be a Potential Hotspot Mutation in the Chinese Population

Piao Y et al.·J Clin Res Pediatr Endocrinol

2024Open Access

Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias.

Koprulu M et al.·Yale J Biol Med

2023Open Access

Natural history of facial and skeletal features from neonatal period to adulthood in a 3M syndrome cohort with biallelic CUL7 or OBSL1 variants.

Tüysüz B et al.·Eur J Med Genet

2021Cohort

Murine obscurin and Obsl1 have functionally redundant roles in sarcolemmal integrity, sarcoplasmic reticulum organization, and muscle metabolism.

Blondelle J et al.·Commun Biol

2019Open AccessFunctional

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

OBSL1

Primary Disease Associations & Inheritance

Clinical highlights

Population Genetics & Constraint

ClinVar Variant Classifications

Protein Context — Lollipop Plot

Mechanism of Pathogenicity

Tissue Expression

Transcripts & Isoforms

Transcript architecture

DECIPHER · Gene2Phenotype

OMIM — Genotype-Phenotype Relationships

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Clinical Trials

External Resources

Transcripts & Isoforms

Mechanism of Pathogenicity