IFT57

intraflagellar transport 57, the group of IFT-B2 complex

Basic information

Region (hg38): 3:108160812-108222435

Previous symbols: [ "ESRRBL1" ]

Links

ENSG00000114446 ∙ NCBI:55081 ∙ OMIM:606621 ∙ HGNC:17367 ∙ Uniprot:Q9NWB7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• orofaciodigital syndrome 18 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Orofaciodigital syndrome XVIII	AR	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; Musculoskeletal	27060890

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFT57 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFT57 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				32	7	39
missense			71	4	2	77
nonsense			2			2
start loss					1	1
frameshift			7			7
inframe indel			1			1
splice donor/acceptor (+/-2bp)			3			3
splice region		1	7	6		14
non coding			2	24	6	32
Total	0	0	86	60	16

Variants in IFT57

This is a list of pathogenic ClinVar variants found in the IFT57 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-108162481-TA-T			Uncertain significance (Aug 27, 2023)
3-108162482-A-C			Uncertain significance (May 15, 2023)
3-108162486-G-T			Likely benign (Aug 27, 2023)
3-108162493-G-A			Uncertain significance (Apr 06, 2022)
3-108162496-G-C			Uncertain significance (Nov 29, 2021)
3-108162535-T-C		IFT57-related disorder	Benign (Jan 29, 2024)
3-108162558-T-C			Likely benign (Jan 18, 2024)
3-108162558-T-G			Uncertain significance (Feb 06, 2022)
3-108162561-G-C			Likely benign (Jul 07, 2023)
3-108162570-G-A		IFT57-related disorder	Likely benign (Oct 13, 2022)
3-108162574-T-C			Uncertain significance (Dec 14, 2022)
3-108162586-A-G			Uncertain significance (Apr 24, 2023)
3-108162599-T-C		Orofaciodigital syndrome 18	Uncertain significance (Mar 05, 2018)
3-108162605-C-T			Uncertain significance (May 22, 2023)
3-108162621-T-C			Likely benign (Dec 07, 2023)
3-108162628-A-G			Uncertain significance (Dec 22, 2023)
3-108162633-C-G			Uncertain significance (Aug 09, 2022)
3-108162648-C-A		not specified	Uncertain significance (Dec 22, 2023)
3-108162661-G-A			Likely benign (Mar 08, 2023)
3-108163651-G-A			Benign (Dec 22, 2023)
3-108163674-A-G			Uncertain significance (Dec 22, 2023)
3-108163675-T-G			Uncertain significance (Nov 19, 2023)
3-108163684-C-T		not specified	Uncertain significance (May 02, 2024)
3-108163742-C-T			Likely benign (Jun 04, 2022)
3-108165420-T-C			Likely benign (Sep 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFT57	protein_coding	protein_coding	ENST00000264538	11	61759

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.33e-10	0.512	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.302	217	230	0.944	0.0000116	2821
Missense in Polyphen		49	56.362	0.86938		745
Synonymous	-0.155	86	84.2	1.02	0.00000426	772
Loss of Function	1.19	18	24.4	0.739	0.00000120	311

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000182	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.000388	0.000381
Finnish	0.0000523	0.0000462
European (Non-Finnish)	0.000252	0.000246
Middle Eastern	0.000388	0.000381
South Asian	0.000328	0.000327
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the formation of cilia. Plays an indirect role in sonic hedgehog signaling, cilia being required for all activity of the hedgehog pathway (By similarity). Has pro- apoptotic function via its interaction with HIP1, leading to recruit caspase-8 (CASP8) and trigger apoptosis. Has the ability to bind DNA sequence motif 5'-AAAGACATG-3' present in the promoter of caspase genes such as CASP1, CASP8 and CASP10, suggesting that it may act as a transcription regulator; however the relevance of such function remains unclear. {ECO:0000250, ECO:0000269|PubMed:11788820, ECO:0000269|PubMed:17107665, ECO:0000269|PubMed:17623017}.
• Disease: DISEASE: Orofaciodigital syndrome 18 (OFD18) [MIM:617927]: A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD18 is an autosomal recessive form characterized by short stature, brachymesophalangy, pre- and postaxial polysyndactyly, and stocky femoral necks, as well as oral anomalies and dysmorphic facial features. {ECO:0000269|PubMed:27060890}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Huntington,s disease - Homo sapiens (human);Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.221

Intolerance Scores

• loftool: 0.319
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.77

Haploinsufficiency Scores

• pHI: 0.151
• hipred: N
• hipred_score: 0.324
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.681

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ift57
• Phenotype: limbs/digits/tail 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); vision/eye phenotype; skeleton phenotype; embryo 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; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: ift57
• Affected structure: retinal rod cell
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: neural tube closure;heart looping;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;smoothened signaling pathway;intraciliary transport involved in cilium assembly;intraciliary transport;regulation of apoptotic process;motile cilium assembly;negative regulation of epithelial cell proliferation;left/right pattern formation;non-motile cilium assembly
• Cellular component: Golgi apparatus;centrosome;cilium;axoneme;intraciliary transport particle B;photoreceptor connecting cilium;ciliary basal body;dendrite terminus;ciliary tip
• Molecular function: DNA binding;protein binding