GeneBe

OBSL1

obscurin like cytoskeletal adaptor 1, the group of I-set domain containing

Basic information

Region (hg38): 2:219550728-219571859

Links

ENSG00000124006 ∙ NCBI:23363 ∙ OMIM:610991 ∙ HGNC:29092 ∙ Uniprot:O75147 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • 3M syndrome 2 (Definitive), mode of inheritance: AR
  • 3M syndrome 2 (Strong), mode of inheritance: AR
  • 3-M syndrome (Supportive), mode of inheritance: AR
  • 3M syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Three M syndrome 2ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Endocrine; Musculoskeletal19481195; 23457316; 27796265

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OBSL1 gene.

  • not_provided (901 variants)
  • Inborn_genetic_diseases (358 variants)
  • 3M_syndrome_2 (248 variants)
  • not_specified (100 variants)
  • OBSL1-related_disorder (51 variants)
  • 3M_syndrome_1 (3 variants)
  • Short_stature (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OBSL1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015311.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
20
clinvar
280
clinvar
22
clinvar
 323
missense
1
clinvar
623
clinvar
58
clinvar
12
clinvar
 694
nonsense
11
clinvar
8
clinvar
10
clinvar
2
clinvar
 31
start loss
1
 1
frameshift
20
clinvar
23
clinvar
17
clinvar
1
clinvar
 61
splice donor/acceptor (+/-2bp)
14
clinvar
2
clinvar
2
clinvar
 18
Total 32 47 672 343 34

Highest pathogenic variant AF is 0.000345412

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
OBSL1protein_codingprotein_codingENST00000404537 2121131
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
9.99e-260.722123979211601251410.00465
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.0068511701.17e+30.9990.000077611872
Missense in Polyphen427426.771.00054414
Synonymous-0.1935175111.010.00003474136
Loss of Function2.425173.40.6950.00000410750

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.01660.0159
Ashkenazi Jewish0.01540.0153
East Asian0.002840.00278
Finnish0.004230.00423
European (Non-Finnish)0.003680.00363
Middle Eastern0.002840.00278
South Asian0.001610.00157
Other0.006660.00657

dbNSFP

Source: dbNSFP

Function
FUNCTION: Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer (PubMed:24793695, PubMed:24793696). Acts as a regulator of the Cul7-RING(FBXW8) ubiquitin-protein ligase, playing a critical role in the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. Required to localize CUL7 to the Golgi apparatus in neurons. {ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}.;
Pathway
Post-translational protein modification;Metabolism of proteins;Neddylation (Consensus)

Intolerance Scores

loftool
0.861
rvis_EVS
-0.81
rvis_percentile_EVS
12.02

Haploinsufficiency Scores

pHI
0.183
hipred
N
hipred_score
0.478
ghis
0.571

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.831

Gene Damage Prediction

AllRecessiveDominant
MendelianHighMediumMedium
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Obsl1
Phenotype

Gene ontology

Biological process
microtubule cytoskeleton organization;muscle contraction;cytoskeleton organization;Golgi organization;regulation of mitotic nuclear division;skeletal muscle thin filament assembly;skeletal muscle myosin thick filament assembly;protein localization to Golgi apparatus;post-translational protein modification;sarcomere organization;cardiac muscle fiber development;positive regulation of dendrite morphogenesis;cardiac myofibril assembly;cardiac muscle tissue morphogenesis;striated muscle myosin thick filament assembly
Cellular component
cytoplasm;Golgi apparatus;centrosome;cytosol;striated muscle thin filament;intercalated disc;sarcomere;Z disc;M band;perinuclear region of cytoplasm;3M complex
Molecular function
protein binding;cytoskeletal adaptor activity;structural constituent of muscle;actin filament binding;muscle alpha-actinin binding