IFT172

intraflagellar transport 172, the group of IFT-B2 complex|WD repeat domain containing

Basic information

Region (hg38): 2:27444376-27489805

Links

ENSG00000138002 ∙ NCBI:26160 ∙ OMIM:607386 ∙ HGNC:30391 ∙ Uniprot:Q9UG01 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• short-rib thoracic dysplasia 9 with or without polydactyly (Definitive), mode of inheritance: AR
• short-rib thoracic dysplasia 10 with or without polydactyly (Moderate), mode of inheritance: AR
• retinitis pigmentosa 71 (Moderate), mode of inheritance: AR
• Jeune syndrome (Supportive), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• short-rib thoracic dysplasia 9 with or without polydactyly (Supportive), mode of inheritance: AR
• short-rib thoracic dysplasia 10 with or without polydactyly (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 20 (Strong), mode of inheritance: AR
• retinitis pigmentosa 71 (Strong), mode of inheritance: AR
• short-rib thoracic dysplasia 10 with or without polydactyly (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 20	AR	Endocrine	Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	24140113; 24290075; 25168386; 26763875; 32451492; 36356613
In Short -rib thoracic dysplasia and Bardet-Biedl syndrome, renal transplantation has been desribed

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFT172 gene.

• Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71 (750 variants)
• Retinitis pigmentosa 71;Short-rib thoracic dysplasia 10 with or without polydactyly (416 variants)
• not provided (208 variants)
• Inborn genetic diseases (80 variants)
• IFT172-related condition (72 variants)
• Short-rib thoracic dysplasia 10 with or without polydactyly;Bardet-Biedl syndrome 20;Retinitis pigmentosa 71 (53 variants)
• not specified (45 variants)
• Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71;Bardet-Biedl syndrome 20 (45 variants)
• Retinitis pigmentosa 71;Bardet-Biedl syndrome 20;Short-rib thoracic dysplasia 10 with or without polydactyly (36 variants)
• Bardet-Biedl syndrome 20;Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71 (35 variants)
• Retinitis pigmentosa 71;Short-rib thoracic dysplasia 10 with or without polydactyly;Bardet-Biedl syndrome 20 (20 variants)
• Bardet-Biedl syndrome 20;Retinitis pigmentosa 71;Short-rib thoracic dysplasia 10 with or without polydactyly (17 variants)
• Short-rib thoracic dysplasia 10 with or without polydactyly (15 variants)
• Retinitis pigmentosa 71 (11 variants)
• Bardet-Biedl syndrome (5 variants)
• Short-rib thoracic dysplasia 10 without polydactyly (5 variants)
• Retinal dystrophy (4 variants)
• Retinitis pigmentosa (3 variants)
• Short-rib thoracic dysplasia 10 with polydactyly (2 variants)
• Bardet-Biedl syndrome 22 (2 variants)
• Bardet-Biedl syndrome 20 (2 variants)
• Anophthalmia-microphthalmia syndrome (2 variants)
• Bardet-Biedl syndrome 1 (1 variants)
• Retinitis pigmentosa 71;Asphyxiating thoracic dystrophy 1 (1 variants)
• Neurodevelopmental disorder (1 variants)
• Nephronophthisis (1 variants)
• Familial aplasia of the vermis (1 variants)
• Short-rib thoracic dysplasia 6 with or without polydactyly (1 variants)
• IFT172-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFT172 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			6	233	3	242
missense	1	3	592	20	5	621
nonsense	19	11				30
start loss						0
frameshift	24	3		1		28
inframe indel			13			13
splice donor/acceptor (+/-2bp)	3	17	1			21
splice region			37	51	3	91
non coding			7	201	33	241
Total	47	34	619	455	41

Highest pathogenic variant AF is 0.0000525

Variants in IFT172

This is a list of pathogenic ClinVar variants found in the IFT172 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-27444430-A-G		not specified • Retinal dystrophy	Benign (Oct 01, 2023)
2-27444437-G-C		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Uncertain significance (Mar 25, 2021)
2-27444446-A-G		Retinal dystrophy	Uncertain significance (Oct 01, 2023)
2-27444453-G-T		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
2-27444454-C-G		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Uncertain significance (Aug 04, 2023)
2-27444470-A-C		Retinitis pigmentosa 71;Short-rib thoracic dysplasia 10 with or without polydactyly	Uncertain significance (Jul 17, 2023)
2-27444472-CACT-C		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Uncertain significance (Feb 28, 2021)
2-27444478-C-T		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Uncertain significance (Aug 21, 2022)
2-27444494-C-T		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Uncertain significance (Nov 08, 2022)
2-27444495-G-A		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71 • Bardet-Biedl syndrome 20;Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71 • Retinal dystrophy	Benign/Likely benign (Jan 02, 2024)
2-27444500-G-T		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Uncertain significance (Jul 13, 2020)
2-27444503-A-G		Short-rib thoracic dysplasia 10 with or without polydactyly • Retinitis pigmentosa 71;Short-rib thoracic dysplasia 10 with or without polydactyly • Retinitis pigmentosa • Bardet-Biedl syndrome 20;Retinitis pigmentosa 71;Short-rib thoracic dysplasia 10 with or without polydactyly	Pathogenic (Aug 04, 2023)
2-27444510-GCTGTGGGAGGT-G		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Pathogenic (Jul 16, 2023)
2-27444512-T-C		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Uncertain significance (Sep 12, 2021)
2-27444512-T-G		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Uncertain significance (Jul 05, 2022)
2-27444526-G-A		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Likely benign (Oct 31, 2022)
2-27444526-G-C		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Likely benign (Jan 21, 2024)
2-27444533-T-C		Retinitis pigmentosa 71;Short-rib thoracic dysplasia 10 with or without polydactyly	Likely benign (Jan 14, 2024)
2-27444541-C-T		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71 • Short-rib thoracic dysplasia 10 with or without polydactyly;Bardet-Biedl syndrome 20;Retinitis pigmentosa 71	Benign/Likely benign (Dec 11, 2023)
2-27444653-T-TTTTG			Benign (Jun 26, 2018)
2-27444951-G-GT			Benign (Aug 06, 2019)
2-27444998-A-C		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Likely benign (May 30, 2022)
2-27444999-G-A		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Likely benign (Oct 08, 2023)
2-27444999-GTCC-G		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Likely benign (May 22, 2023)
2-27445000-T-C		Short-rib thoracic dysplasia 10 with or without polydactyly;Retinitis pigmentosa 71	Likely benign (Mar 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFT172	protein_coding	protein_coding	ENST00000260570	48	45419

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.27e-33	1.00	125578	0	170	125748	0.000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	892	997	0.894	0.0000567	11423
Missense in Polyphen		219	299	0.73245		3452
Synonymous	1.27	338	369	0.916	0.0000203	3352
Loss of Function	3.77	71	115	0.619	0.00000624	1265

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00166	0.00165
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.000872	0.000870
Finnish	0.000280	0.000277
European (Non-Finnish)	0.000645	0.000642
Middle Eastern	0.000872	0.000870
South Asian	0.00101	0.00101
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the maintenance and formation of cilia. Plays an indirect role in hedgehog (Hh) signaling, cilia being required for all activity of the hedgehog pathway (By similarity). {ECO:0000250}.
• Disease: DISEASE: Short-rib thoracic dysplasia 10 with or without polydactyly (SRTD10) [MIM:615630]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:24140113}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 71 (RP71) [MIM:616394]: 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:25168386}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hedgehog signaling events mediated by Gli proteins;Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.162

Intolerance Scores

• loftool: 0.960
• rvis_EVS: -1.96
• rvis_percentile_EVS: 1.86

Haploinsufficiency Scores

• pHI: 0.253
• hipred: N
• hipred_score: 0.368
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.706

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ift172
• Phenotype: 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); 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); respiratory system phenotype; embryo phenotype; skeleton phenotype; renal/urinary system phenotype; vision/eye phenotype; digestive/alimentary 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); growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: ift172
• Affected structure: retinal cone cell
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: neural tube closure;heart looping;Notch signaling pathway;smoothened signaling pathway;brain development;epidermis development;dorsal/ventral pattern formation;protein processing;spinal cord motor neuron differentiation;cytoplasmic microtubule organization;intraciliary transport involved in cilium assembly;positive regulation of smoothened signaling pathway;negative regulation of epithelial cell proliferation;roof of mouth development;limb development;cilium assembly;bone development;hindgut development;left/right axis specification;non-motile cilium assembly
• Cellular component: cilium;axoneme;intraciliary transport particle B;ciliary basal body;sperm midpiece;sperm principal piece;ciliary tip;sperm cytoplasmic droplet;extracellular vesicle