IFT122

intraflagellar transport 122, the group of IFT-A complex|WD repeat domain containing

Basic information

Region (hg38): 3:129429607-129520510

Previous symbols: [ "WDR10" ]

Links

ENSG00000163913 ∙ NCBI:55764 ∙ OMIM:606045 ∙ HGNC:13556 ∙ Uniprot:Q9HBG6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cranioectodermal dysplasia 1 (Definitive), mode of inheritance: AR
• cranioectodermal dysplasia 1 (Strong), mode of inheritance: AR
• cranioectodermal dysplasia (Supportive), mode of inheritance: AR
• cranioectodermal dysplasia 1 (Strong), mode of inheritance: AR
• cranioectodermal dysplasia 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cranioectodermal dysplasia 1; Sensenbrenner syndrome	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; Dental; Dermatologic; Musculoskeletal	17022080; 19760620; 20493458

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFT122 gene.

• Cranioectodermal dysplasia 1 (25 variants)
• not provided (4 variants)
• Cranioectodermal dysplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFT122 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			10	135	2	147
missense		7	248	15		270
nonsense	13	2				15
start loss						0
frameshift	14	2	2			18
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	4				5
splice region			17	25	1	43
non coding			9	110	58	177
Total	28	15	272	260	60

Highest pathogenic variant AF is 0.0000197

Variants in IFT122

This is a list of pathogenic ClinVar variants found in the IFT122 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-129431510-A-C			Uncertain significance (Dec 17, 2023)
3-129431522-A-G			Likely benign (Dec 05, 2023)
3-129431523-T-C			Uncertain significance (Nov 03, 2023)
3-129431538-C-T		Melanoma, uveal, susceptibility to, 1	Uncertain significance (Oct 29, 2023)
3-129431540-G-A			Likely benign (Jan 24, 2024)
3-129431542-C-G		not specified	Conflicting classifications of pathogenicity (Aug 01, 2024)
3-129431544-T-C			Uncertain significance (Mar 19, 2023)
3-129431545-G-A			Uncertain significance (Jan 20, 2023)
3-129431547-T-C			Uncertain significance (Jan 28, 2024)
3-129431549-T-C			Likely benign (Dec 27, 2023)
3-129431556-A-T		Melanoma, uveal, susceptibility to, 1 • Tumor predisposition syndrome 2	Conflicting classifications of pathogenicity (Jan 29, 2024)
3-129431559-T-C			Uncertain significance (Dec 27, 2023)
3-129431588-A-G			Uncertain significance (Dec 12, 2023)
3-129431590-A-G			Uncertain significance (Jan 24, 2024)
3-129431595-A-C			Uncertain significance (Jan 17, 2024)
3-129431596-T-C			Likely benign (Dec 10, 2023)
3-129431598-C-G			Likely benign (Dec 18, 2023)
3-129431751-A-C			Benign (May 13, 2021)
3-129432443-G-A		MBD4-related disorder	Likely benign (Dec 30, 2022)
3-129432483-T-C			Likely benign (Jan 04, 2024)
3-129432487-T-C			Likely benign (Jun 09, 2022)
3-129432490-G-C			Likely benign (Jan 18, 2024)
3-129432492-G-A			Likely benign (Nov 25, 2023)
3-129432500-C-T			Uncertain significance (Jan 02, 2024)
3-129432513-T-A			Uncertain significance (Dec 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFT122	protein_coding	protein_coding	ENST00000296266	31	80231

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.38e-24	0.883	125598	1	149	125748	0.000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.346	689	715	0.964	0.0000455	8514
Missense in Polyphen		215	227.67	0.94435		2656
Synonymous	0.364	275	283	0.972	0.0000180	2433
Loss of Function	2.56	49	72.5	0.676	0.00000375	871

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00191	0.00191
Ashkenazi Jewish	0.00	0.00
East Asian	0.000761	0.000761
Finnish	0.000508	0.000508
European (Non-Finnish)	0.000573	0.000563
Middle Eastern	0.000761	0.000761
South Asian	0.000392	0.000392
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for cilia formation during neuronal patterning. Acts as a negative regulator of Shh signaling. Required to recruit TULP3 to primary cilia (By similarity). {ECO:0000250}.
• Pathway: Signal Transduction;Hedgehog ,off, state;Signaling by Hedgehog;Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.945
• rvis_EVS: -1.27
• rvis_percentile_EVS: 5.21

Haploinsufficiency Scores

• pHI: 0.371
• hipred: Y
• hipred_score: 0.540
• ghis: 0.593

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.500

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ift122
• Phenotype: craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region 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; vision/eye 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)

Zebrafish Information Network

• Gene name: ift122
• Affected structure: hair cell
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: neural tube closure;signal transduction downstream of smoothened;embryonic body morphogenesis;negative regulation of smoothened signaling pathway involved in ventral spinal cord patterning;embryonic heart tube development;embryonic forelimb morphogenesis;intraciliary anterograde transport;intraciliary retrograde transport;intraciliary transport involved in cilium assembly;embryonic digit morphogenesis;negative regulation of smoothened signaling pathway;camera-type eye morphogenesis;negative regulation of epithelial cell proliferation;limb development;cilium assembly;ciliary receptor clustering involved in smoothened signaling pathway;smoothened signaling pathway involved in dorsal/ventral neural tube patterning;embryonic heart tube left/right pattern formation;protein localization to cilium;establishment of protein localization to organelle;non-motile cilium assembly
• Cellular component: nucleoplasm;cytosol;cilium;membrane;intraciliary transport particle A;photoreceptor connecting cilium;ciliary basal body;ciliary tip;ciliary base
• Molecular function: protein binding