OFD1

OFD1 centriole and centriolar satellite protein

Basic information

Region (hg38): X:13734743-13777955

Previous symbols: [ "CXorf5", "RP23" ]

Links

ENSG00000046651NCBI:8481OMIM:300170HGNC:2567Uniprot:O75665AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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
  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Orofaciodigital syndrome 1; Simpson-Golabi-Behmel syndrome type 2; Joubert syndrome 10; Retinitis pigmentosa 23XLGeneralGenetic 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; Dental; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Pulmonary; Renal15444577; 13707262; 1248177; 11179005; 16783569; 16397067; 19800048; 20301500; 20301367; 20818665; 21729220; 22353940; 22548404; 22619378; 23033313

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OFD1 gene.

  • not provided (26 variants)
  • Orofaciodigital syndrome I (18 variants)
  • Orofaciodigital syndrome I;Familial aplasia of the vermis (17 variants)
  • Familial aplasia of the vermis;Orofaciodigital syndrome I (13 variants)
  • Primary ciliary dyskinesia (8 variants)
  • Joubert syndrome 10 (5 variants)
  • OFD1-related disorder (4 variants)
  • Simpson-Golabi-Behmel syndrome type 2 (2 variants)
  • Inborn genetic diseases (2 variants)
  • Orofaciodigital syndrome I;Joubert syndrome 10;Retinitis pigmentosa 23;Simpson-Golabi-Behmel syndrome type 2 (2 variants)
  • Joubert syndrome 10;Orofaciodigital syndrome I;Retinitis pigmentosa 23;Simpson-Golabi-Behmel syndrome type 2 (2 variants)
  • Simpson-Golabi-Behmel syndrome (1 variants)
  • Orofacial-digital syndrome III (1 variants)
  • Orofaciodigital syndrome I;Joubert syndrome 10;Simpson-Golabi-Behmel syndrome type 2 (1 variants)
  • Retinitis pigmentosa 23;Orofaciodigital syndrome I;Joubert syndrome 10;Simpson-Golabi-Behmel syndrome type 2 (1 variants)
  • COACH syndrome (1 variants)
  • Retinal dystrophy (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.

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.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
8
clinvar
133
clinvar
7
clinvar
148
missense
4
clinvar
3
clinvar
364
clinvar
28
clinvar
12
clinvar
411
nonsense
20
clinvar
5
clinvar
25
start loss
1
clinvar
2
clinvar
3
frameshift
39
clinvar
10
clinvar
2
clinvar
51
inframe indel
3
clinvar
17
clinvar
20
splice donor/acceptor (+/-2bp)
8
clinvar
13
clinvar
6
clinvar
27
splice region
3
20
27
1
51
non coding
2
clinvar
20
clinvar
110
clinvar
42
clinvar
174
Total 73 35 419 271 61

Highest pathogenic variant AF is 0.00000890

Variants in OFD1

This is a list of pathogenic ClinVar variants found in the OFD1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
X-13734757-G-C Likely benign (Feb 04, 2019)1218894
X-13734776-G-T Benign (Jun 26, 2018)41157
X-13735032-C-T Uncertain significance (Feb 24, 2022)1677963
X-13735053-C-G Likely benign (Mar 19, 2018)680448
X-13735072-A-G Simpson-Golabi-Behmel syndrome type 2;Retinitis pigmentosa 23;Joubert syndrome 10;Orofaciodigital syndrome I Uncertain significance (Feb 06, 2024)3598057
X-13735072-AT-A Likely pathogenic (May 09, 2023)2690660
X-13735074-G-A Orofaciodigital syndrome I;Familial aplasia of the vermis • Primary ciliary dyskinesia • Joubert syndrome 10 Uncertain significance (Jan 05, 2025)1031340
X-13735075-A-G Orofaciodigital syndrome I;Familial aplasia of the vermis Uncertain significance (Oct 11, 2023)2937537
X-13735078-G-T Orofaciodigital syndrome I;Familial aplasia of the vermis Uncertain significance (Aug 11, 2023)2935770
X-13735079-C-A Familial aplasia of the vermis;Orofaciodigital syndrome I • Primary ciliary dyskinesia Uncertain significance (Dec 24, 2024)2475764
X-13735091-C-T Orofaciodigital syndrome I;Familial aplasia of the vermis Likely benign (Feb 11, 2022)2092854
X-13735093-C-A Orofaciodigital syndrome I;Familial aplasia of the vermis Likely benign (Mar 03, 2022)1158105
X-13735099-C-T Familial aplasia of the vermis;Orofaciodigital syndrome I Benign (Oct 22, 2024)1532880
X-13735101-T-A Orofaciodigital syndrome I;Familial aplasia of the vermis Likely benign (Jan 24, 2025)2946640
X-13735103-C-T Orofaciodigital syndrome I;Familial aplasia of the vermis Likely benign (Oct 06, 2024)3760983
X-13735111-G-C not specified Benign/Likely benign (Mar 14, 2020)211784
X-13735162-T-G Benign (Jun 30, 2018)1235588
X-13735189-T-G Likely benign (Jul 06, 2018)1205624
X-13735228-A-G Orofaciodigital syndrome I;Familial aplasia of the vermis Likely benign (Apr 25, 2024)3758293
X-13735241-C-A Familial aplasia of the vermis;Orofaciodigital syndrome I Likely benign (Jul 21, 2023)1663560
X-13735251-A-G Orofaciodigital syndrome I;Familial aplasia of the vermis Uncertain significance (Oct 25, 2023)2927343
X-13735252-A-G Orofaciodigital syndrome I;Familial aplasia of the vermis Uncertain significance (Aug 21, 2022)2099476
X-13735254-A-G Orofaciodigital syndrome I;Familial aplasia of the vermis Uncertain significance (Jan 06, 2025)3761662
X-13735254-A-T Orofaciodigital syndrome I;Familial aplasia of the vermis Uncertain significance (May 21, 2024)3756462
X-13735261-C-T Orofaciodigital syndrome I;Familial aplasia of the vermis • Orofaciodigital syndrome I;Retinitis pigmentosa 23;Simpson-Golabi-Behmel syndrome type 2;Joubert syndrome 10 Uncertain significance (May 18, 2024)463455

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
OFD1protein_codingprotein_codingENST00000340096 2334649
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9600.040312568619391257440.000231
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.3203503670.9530.00002766701
Missense in Polyphen6289.3680.693761990
Synonymous-0.5081431351.060.00001051807
Loss of Function4.91740.90.1710.00000309719

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0006990.000685
Ashkenazi Jewish0.002690.00199
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.0002200.000158
Middle Eastern0.000.00
South Asian0.000.00
Other0.0004460.000326

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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