OFD1
OFD1 centriole and centriolar satellite protein
Basic information
Region (hg38): X:13734743-13777955
Previous symbols: [ "CXorf5", "RP23" ]
Links
Phenotypes
GenCC
Source:
- retinitis pigmentosa (Supportive), mode of inheritance: AD
- primary ciliary dyskinesia (Supportive), mode of inheritance: AD
- orofaciodigital syndrome I (Supportive), mode of inheritance: XL
- orofaciodigital syndrome type 6 (Supportive), mode of inheritance: AR
- orofaciodigital syndrome I (Strong), mode of inheritance: XL
- Simpson-Golabi-Behmel syndrome type 2 (Limited), mode of inheritance: XL
- Joubert syndrome 10 (Definitive), mode of inheritance: XL
- retinitis pigmentosa 23 (Strong), mode of inheritance: XL
- orofaciodigital syndrome I (Definitive), mode of inheritance: XL
- Joubert syndrome 10 (Strong), mode of inheritance: XL
- retinitis pigmentosa 23 (Strong), mode of inheritance: XL
- ciliopathy (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Orofaciodigital syndrome 1; Simpson-Golabi-Behmel syndrome type 2; Joubert syndrome 10; Retinitis pigmentosa 23 | XL | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Dental; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Pulmonary; Renal | 15444577; 13707262; 1248177; 11179005; 16783569; 16397067; 19800048; 20301500; 20301367; 20818665; 21729220; 22353940; 22548404; 22619378; 23033313 |
ClinVar
This is a list of variants' phenotypes submitted to
- Orofaciodigital_syndrome_I (810 variants)
- Joubert_syndrome (713 variants)
- not_provided (265 variants)
- Primary_ciliary_dyskinesia (191 variants)
- Joubert_syndrome_10 (148 variants)
- Simpson-Golabi-Behmel_syndrome_type_2 (141 variants)
- Retinitis_pigmentosa_23 (135 variants)
- not_specified (61 variants)
- OFD1-related_disorder (50 variants)
- Retinal_dystrophy (21 variants)
- Intellectual_disability (6 variants)
- Inborn_genetic_diseases (4 variants)
- Simpson-Golabi-Behmel_syndrome (2 variants)
- History_of_neurodevelopmental_disorder (2 variants)
- OFD1-related_ciliopathy (2 variants)
- Peripheral_precocious_puberty (2 variants)
- Orofacial-digital_syndrome_III (1 variants)
- Ridged_nail (1 variants)
- Bifid_nail (1 variants)
- Respiratory_ciliopathies_including_non-CF_bronchiectasis (1 variants)
- Orofaciodigital_syndrome (1 variants)
- Osteoporosis (1 variants)
- Ciliopathy (1 variants)
- Rare_genetic_intellectual_disability (1 variants)
- Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
- Polydactyly,_postaxial,_type_A1 (1 variants)
- Cerebral_arteriopathy,_autosomal_dominant,_with_subcortical_infarcts_and_leukoencephalopathy,_type_1 (1 variants)
- Ventriculomegaly (1 variants)
- Polymicrogyria (1 variants)
- Cerebellar_vermis_hypoplasia (1 variants)
- See_cases (1 variants)
- COACH_syndrome (1 variants)
- Congenital_cerebellar_hypoplasia (1 variants)
- Kidney_failure (1 variants)
- Abnormal_nail_morphology (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the OFD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003611.3. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 27 | 165 | 199 | |||
| missense | 492 | 77 | 592 | |||
| nonsense | 21 | 15 | 44 | |||
| start loss | 1 | 2 | 3 | |||
| frameshift | 51 | 21 | 78 | |||
| splice donor/acceptor (+/-2bp) | 12 | 20 | 38 | 72 | ||
| Total | 90 | 58 | 579 | 245 | 16 |
Highest pathogenic variant AF is 0.00006057824
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| OFD1 | protein_coding | protein_coding | ENST00000340096 | 23 | 34649 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.960 | 0.0403 | 125686 | 19 | 39 | 125744 | 0.000231 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.320 | 350 | 367 | 0.953 | 0.0000276 | 6701 |
| Missense in Polyphen | 62 | 89.368 | 0.69376 | 1990 | ||
| Synonymous | -0.508 | 143 | 135 | 1.06 | 0.0000105 | 1807 |
| Loss of Function | 4.91 | 7 | 40.9 | 0.171 | 0.00000309 | 719 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000699 | 0.000685 |
| Ashkenazi Jewish | 0.00269 | 0.00199 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000220 | 0.000158 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000446 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164. Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis. Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which is an important step in the ciliogenesis regulation (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Simpson-Golabi-Behmel syndrome 2 (SGBS2) [MIM:300209]: A severe variant of Simpson-Golabi-Behmel syndrome, a condition characterized by pre- and postnatal overgrowth (gigantism), facial dysmorphism and a variety of inconstant visceral and skeletal malformations. {ECO:0000269|PubMed:16783569}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Joubert syndrome 10 (JBTS10) [MIM:300804]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. {ECO:0000269|PubMed:19800048, ECO:0000269|PubMed:26477546}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 23 (RP23) [MIM:300424]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:22619378}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
- Pathway
- Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.178
Intolerance Scores
- loftool
- 0.117
- rvis_EVS
- -0.18
- rvis_percentile_EVS
- 40.56
Haploinsufficiency Scores
- pHI
- 0.110
- hipred
- Y
- hipred_score
- 0.583
- ghis
- 0.554
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.810
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ofd1
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); craniofacial phenotype; cellular phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- ofd1
- Affected structure
- otolith
- Phenotype tag
- abnormal
- Phenotype quality
- decreased size
Gene ontology
- Biological process
- G2/M transition of mitotic cell cycle;mitotic cell cycle;centriole replication;regulation of G2/M transition of mitotic cell cycle;cilium assembly;epithelial cilium movement involved in determination of left/right asymmetry;mitotic spindle assembly;ciliary basal body-plasma membrane docking
- Cellular component
- nucleus;centrosome;centriole;cytosol;cilium;membrane;centriolar satellite;ciliary basal body
- Molecular function
- protein binding;identical protein binding;alpha-tubulin binding;gamma-tubulin binding