IFT140

intraflagellar transport 140, the group of IFT-A complex|WD repeat domain containing

Basic information

Region (hg38): 16:1510427-1612072

Previous symbols: [ "WDTC2" ]

Links

ENSG00000187535 ∙ NCBI:9742 ∙ OMIM:614620 ∙ HGNC:29077 ∙ Uniprot:Q96RY7 ∙ 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
• Jeune syndrome (Supportive), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• short-rib thoracic dysplasia 9 with or without polydactyly (Supportive), mode of inheritance: AR
• IFT140-related recessive ciliopathy (Definitive), mode of inheritance: AR
• short-rib thoracic dysplasia 9 with or without polydactyly (Strong), mode of inheritance: AR
• retinitis pigmentosa 80 (Strong), mode of inheritance: AR
• autosomal dominant polycystic kidney disease (Definitive), mode of inheritance: AD
• IFT140-related recessive ciliopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short-rib thoracic dysplasia 9 with or without polydactyly; Retinitis pigmentosa 80	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	Musculoskeletal; Neurologic; Ophthalmologic; Renal	22503633; 23418020; 24698627; 26216056; 26359340; 26968735
Variants may modify ciliopathies due to variants in other genes

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFT140 gene.

• Saldino-Mainzer syndrome (57 variants)
• IFT140-related disorder (8 variants)
• not provided (6 variants)
• Saldino-Mainzer syndrome;Joubert syndrome with Jeune asphyxiating thoracic dystrophy (4 variants)
• Retinitis pigmentosa (4 variants)
• Retinitis pigmentosa 80 (4 variants)
• Cranioectodermal dysplasia;Saldino-Mainzer syndrome (2 variants)
• Jeune thoracic dystrophy (2 variants)
• Retinal dystrophy (2 variants)
• Saldino-Mainzer syndrome;Retinitis pigmentosa 80 (2 variants)
• Short-rib thoracic dysplasia without polydactyly (1 variants)
• Retinitis pigmentosa 80;Saldino-Mainzer syndrome (1 variants)
• Retinal ciliopathy due to mutation in the retinitis pigmentosa-1 gene (1 variants)
• Autosomal dominant polycystic kidney disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFT140 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	352	12	374
missense	6	5	648	41	15	715
nonsense	25	12	2			39
start loss	1					1
frameshift	28	22	4			54
inframe indel			18			18
splice donor/acceptor (+/-2bp)	5	28	1			34
splice region		1	40	54		95
non coding	1	1	33	203	47	285
Total	66	68	716	596	74

Highest pathogenic variant AF is 0.0000526

Variants in IFT140

This is a list of pathogenic ClinVar variants found in the IFT140 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-1510514-C-T		Saldino-Mainzer syndrome	Uncertain significance (Jan 13, 2018)
16-1510515-G-A		Saldino-Mainzer syndrome	Likely benign (Jan 12, 2018)
16-1510541-C-T		Saldino-Mainzer syndrome	Likely benign (Jan 13, 2018)
16-1510666-G-T		Saldino-Mainzer syndrome	Uncertain significance (Jan 13, 2018)
16-1510709-G-T		Saldino-Mainzer syndrome	Benign (Jan 12, 2018)
16-1510718-A-C		Saldino-Mainzer syndrome	Uncertain significance (Jan 12, 2018)
16-1510737-G-A		Saldino-Mainzer syndrome	Uncertain significance (Jan 13, 2018)
16-1510786-C-G		Saldino-Mainzer syndrome	Uncertain significance (Jan 13, 2018)
16-1510791-G-A		Saldino-Mainzer syndrome	Uncertain significance (Jan 13, 2018)
16-1510826-C-T		Saldino-Mainzer syndrome	Uncertain significance (Jun 14, 2016)
16-1510853-C-A		Saldino-Mainzer syndrome	Uncertain significance (Jan 13, 2018)
16-1510881-T-C		Saldino-Mainzer syndrome	Likely benign (Jan 13, 2018)
16-1510885-A-G		Saldino-Mainzer syndrome • Retinitis pigmentosa 80	Benign (Jul 14, 2021)
16-1510898-A-C		Saldino-Mainzer syndrome	Uncertain significance (Jan 12, 2018)
16-1510921-G-A		Saldino-Mainzer syndrome	Uncertain significance (Jan 13, 2018)
16-1510942-C-T		Saldino-Mainzer syndrome • not specified	Likely benign (Jan 13, 2018)
16-1510945-C-T		Saldino-Mainzer syndrome	Likely benign (Aug 27, 2020)
16-1510945-CAG-C		Saldino-Mainzer syndrome	Uncertain significance (Mar 10, 2020)
16-1510948-G-A		Saldino-Mainzer syndrome	Uncertain significance (Nov 01, 2021)
16-1510950-G-A		Saldino-Mainzer syndrome • Saldino-Mainzer syndrome;Retinitis pigmentosa 80	Likely benign (Nov 24, 2023)
16-1510952-C-T		Saldino-Mainzer syndrome • Saldino-Mainzer syndrome;Retinitis pigmentosa 80 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 09, 2024)
16-1510953-G-A		Saldino-Mainzer syndrome	Benign (Jan 29, 2024)
16-1510954-T-C		Saldino-Mainzer syndrome • Retinitis pigmentosa 80;Saldino-Mainzer syndrome	Uncertain significance (Nov 13, 2021)
16-1510955-C-T		Saldino-Mainzer syndrome • Saldino-Mainzer syndrome;Retinitis pigmentosa 80 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 22, 2023)
16-1510955-C-CT		Saldino-Mainzer syndrome • Retinitis pigmentosa 80;Saldino-Mainzer syndrome	Uncertain significance (Aug 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFT140	protein_coding	protein_coding	ENST00000426508	29	101684

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.91e-24	0.981	125592	0	156	125748	0.000620

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.811	997	928	1.07	0.0000620	9552
Missense in Polyphen		205	222.02	0.92333		2286
Synonymous	-2.16	467	411	1.14	0.0000312	2836
Loss of Function	2.87	49	76.0	0.644	0.00000402	817

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00144	0.00136
Ashkenazi Jewish	0.00248	0.00248
East Asian	0.000494	0.000489
Finnish	0.0000474	0.0000462
European (Non-Finnish)	0.000587	0.000571
Middle Eastern	0.000494	0.000489
South Asian	0.000794	0.000784
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport (PubMed:20889716, PubMed:22503633). Plays a pivotal role in proper development and function of ciliated cells through its role in ciliogenesis and/or cilium maintenance (PubMed:22503633). Required for the development and maintenance of the outer segments of rod and cone photoreceptor cells. Plays a role in maintenance and the delivery of opsin to the outer segment of photoreceptor cells (By similarity). {ECO:0000250|UniProtKB:E9PY46, ECO:0000269|PubMed:20889716, ECO:0000269|PubMed:22503633, ECO:0000269|PubMed:28724397}.
• Disease: DISEASE: Short-rib thoracic dysplasia 9 with or without polydactyly (SRTD9) [MIM:266920]: 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. SRTD9 is characterized by phalangeal cone-shaped epiphyses, chronic renal disease, nearly constant retinal dystrophy, and mild radiographic abnormality of the proximal femur. Occasional features include short stature, cerebellar ataxia, and hepatic fibrosis. {ECO:0000269|PubMed:22503633, ECO:0000269|PubMed:23418020, ECO:0000269|PubMed:24009529, ECO:0000269|PubMed:28288023, ECO:0000269|PubMed:28724397}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 80 (RP80) [MIM:617781]: 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. RP80 inheritance is autosomal recessive. {ECO:0000269|PubMed:26216056, ECO:0000269|PubMed:26359340, ECO:0000269|PubMed:26968735}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Signal Transduction;Hedgehog ,off, state;Signaling by Hedgehog;Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.879
• rvis_EVS: -0.48
• rvis_percentile_EVS: 22.82

Haploinsufficiency Scores

• pHI: 0.297
• hipred: N
• hipred_score: 0.393
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.492

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ift140
• Phenotype: immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; hearing/vestibular/ear 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; vision/eye 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); hematopoietic 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); embryo phenotype; respiratory system phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: ift140
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: determination of left/right symmetry;heart development;regulation of smoothened signaling pathway;neural tube patterning;embryonic camera-type eye development;intraciliary retrograde transport;intraciliary transport involved in cilium assembly;photoreceptor cell outer segment organization;embryonic digit morphogenesis;embryonic cranial skeleton morphogenesis;skeletal system morphogenesis;retina development in camera-type eye;cilium assembly;protein localization to cilium;renal system development;regulation of cilium assembly;non-motile cilium assembly;embryonic brain development
• Cellular component: photoreceptor outer segment;centrosome;cilium;axoneme;intraciliary transport particle A;photoreceptor connecting cilium;ciliary basal body;ciliary tip
• Molecular function: molecular_function