OFD1

OFD1 centriole and centriolar satellite protein

Basic information

Region (hg38): X:13734742-13777955

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

Links

ENSG00000046651 ∙ NCBI:8481 ∙ OMIM:300170 ∙ HGNC:2567 ∙ Uniprot:O75665 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• orofaciodigital syndrome I (Definitive), mode of inheritance: XLD
• Simpson-Golabi-Behmel syndrome type 2 (Definitive), mode of inheritance: XLR
• Joubert syndrome 10 (Definitive), mode of inheritance: XLR
• 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: CGD

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 ClinVar and linked to the OFD1 gene.

• Familial aplasia of the vermis;Orofaciodigital syndrome I (262 variants)
• not provided (231 variants)
• Orofaciodigital syndrome I;Familial aplasia of the vermis (223 variants)
• not specified (51 variants)
• Inborn genetic diseases;Primary ciliary dyskinesia (42 variants)
• Primary ciliary dyskinesia;Inborn genetic diseases (41 variants)
• Inborn genetic diseases (30 variants)
• Orofaciodigital syndrome I (26 variants)
• Joubert syndrome 10 (16 variants)
• OFD1-related condition (10 variants)
• Simpson-Golabi-Behmel syndrome type 2 (10 variants)
• Retinitis pigmentosa 23;Simpson-Golabi-Behmel syndrome type 2;Orofaciodigital syndrome I;Joubert syndrome 10 (9 variants)
• Orofaciodigital syndrome I;Retinitis pigmentosa 23;Simpson-Golabi-Behmel syndrome type 2;Joubert syndrome 10 (8 variants)
• Primary ciliary dyskinesia (7 variants)
• Retinitis pigmentosa 23;Simpson-Golabi-Behmel syndrome type 2;Joubert syndrome 10;Orofaciodigital syndrome I (5 variants)
• Retinitis pigmentosa 23 (4 variants)
• Simpson-Golabi-Behmel syndrome type 2;Retinitis pigmentosa 23;Joubert syndrome 10;Orofaciodigital syndrome I (3 variants)
• Joubert syndrome 10;Orofaciodigital syndrome I;Retinitis pigmentosa 23;Simpson-Golabi-Behmel syndrome type 2 (3 variants)
• Simpson-Golabi-Behmel syndrome type 2;Joubert syndrome 10;Retinitis pigmentosa 23;Orofaciodigital syndrome I (3 variants)
• Simpson-Golabi-Behmel syndrome type 2;Orofaciodigital syndrome I;Joubert syndrome 10 (2 variants)
• Retinitis pigmentosa 23;Joubert syndrome 10;Orofaciodigital syndrome I;Simpson-Golabi-Behmel syndrome type 2 (2 variants)
• History of neurodevelopmental disorder (2 variants)
• Simpson-Golabi-Behmel syndrome type 2;Retinitis pigmentosa 23;Orofaciodigital syndrome I;Joubert syndrome 10 (2 variants)
• Retinitis pigmentosa 23;Orofaciodigital syndrome I;Simpson-Golabi-Behmel syndrome type 2;Joubert syndrome 10 (2 variants)
• - (2 variants)
• OFD1-related ciliopathy (2 variants)
• Orofaciodigital syndrome I;Joubert syndrome 10;Simpson-Golabi-Behmel syndrome type 2;Retinitis pigmentosa 23 (2 variants)
• Simpson-Golabi-Behmel syndrome type 2;Orofaciodigital syndrome I;Joubert syndrome 10;Retinitis pigmentosa 23 (2 variants)
• Retinal dystrophy (2 variants)
• Ventriculomegaly;Polymicrogyria;Cerebellar vermis hypoplasia (1 variants)
• Simpson-Golabi-Behmel syndrome type 2;Joubert syndrome 10 (1 variants)
• Rare genetic intellectual disability (1 variants)
• Orofaciodigital syndrome I;Joubert syndrome 10;Retinitis pigmentosa 23;Simpson-Golabi-Behmel syndrome type 2 (1 variants)
• OFD1-related disorder (1 variants)
• Polydactyly, postaxial, type A1;Bifid nail;Ridged nail;Abnormality of the nail (1 variants)
• COACH syndrome (1 variants)
• Joubert syndrome 10;Retinitis pigmentosa 23;Simpson-Golabi-Behmel syndrome type 2;Orofaciodigital syndrome I (1 variants)
• Congenital anomaly of kidney and urinary tract (1 variants)
• Joubert syndrome 10;Simpson-Golabi-Behmel syndrome type 2;Orofaciodigital syndrome I;Retinitis pigmentosa 23 (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			7	110	8	125
missense	4	2	256	28	13	303
nonsense	15	5				20
start loss		1	1			2
frameshift	32	4	2			38
inframe indel		2	15			17
splice donor/acceptor (+/-2bp)	8	9	4			21
splice region		3	15	23	2	43
non coding	2		8	89	43	142
Total	61	23	293	227	64

Highest pathogenic variant AF is 0.0000179

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)
X-13734776-G-T			Benign (Jun 26, 2018)
X-13735032-C-T			Uncertain significance (Feb 24, 2022)
X-13735053-C-G			Likely benign (Mar 19, 2018)
X-13735072-AT-A			Likely pathogenic (May 09, 2023)
X-13735074-G-A		Joubert syndrome 10 • Orofaciodigital syndrome I;Familial aplasia of the vermis • Primary ciliary dyskinesia	Uncertain significance (Oct 31, 2023)
X-13735075-A-G		Familial aplasia of the vermis;Orofaciodigital syndrome I	Uncertain significance (Oct 11, 2023)
X-13735078-G-T		Familial aplasia of the vermis;Orofaciodigital syndrome I	Uncertain significance (Aug 11, 2023)
X-13735079-C-A		Primary ciliary dyskinesia	Uncertain significance (Jan 11, 2023)
X-13735091-C-T		Familial aplasia of the vermis;Orofaciodigital syndrome I	Likely benign (Feb 11, 2022)
X-13735093-C-A		Orofaciodigital syndrome I;Familial aplasia of the vermis	Likely benign (Mar 03, 2022)
X-13735099-C-T		Familial aplasia of the vermis;Orofaciodigital syndrome I	Benign (Mar 17, 2023)
X-13735101-T-A		Orofaciodigital syndrome I;Familial aplasia of the vermis	Likely benign (Jun 09, 2023)
X-13735111-G-C		not specified	Benign/Likely benign (Mar 14, 2020)
X-13735162-T-G			Benign (Jun 30, 2018)
X-13735189-T-G			Likely benign (Jul 06, 2018)
X-13735241-C-A		Orofaciodigital syndrome I;Familial aplasia of the vermis	Likely benign (Jul 21, 2023)
X-13735251-A-G		Familial aplasia of the vermis;Orofaciodigital syndrome I	Uncertain significance (Oct 25, 2023)
X-13735252-A-G		Familial aplasia of the vermis;Orofaciodigital syndrome I	Uncertain significance (Aug 21, 2022)
X-13735261-C-T		Orofaciodigital syndrome I;Familial aplasia of the vermis	Uncertain significance (Apr 06, 2022)
X-13735263-G-T		Familial aplasia of the vermis;Orofaciodigital syndrome I	Uncertain significance (Feb 28, 2022)
X-13735264-T-C		Familial aplasia of the vermis;Orofaciodigital syndrome I	Uncertain significance (Feb 04, 2019)
X-13735269-G-T		Orofaciodigital syndrome I;Familial aplasia of the vermis	Uncertain significance (Jan 18, 2024)
X-13735273-T-G		OFD1-related disorder	Uncertain significance (Aug 08, 2023)
X-13735277-G-A		Orofaciodigital syndrome I;Familial aplasia of the vermis	Likely benign (Aug 04, 2023)

GnomAD

Source: gnomAD

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: 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

	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