IFT81

intraflagellar transport 81, the group of IFT-B1 complex

Basic information

Region (hg38): 12:110124334-110218793

Previous symbols: [ "CDV1" ]

Links

ENSG00000122970 ∙ NCBI:28981 ∙ OMIM:605489 ∙ HGNC:14313 ∙ Uniprot:Q8WYA0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ciliopathy (Limited), mode of inheritance: AR
• short-rib thoracic dysplasia 19 with or without polydactyly (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short-rib thoracic dysplasia 19 with or without polydactyly	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; Genitourinary; Musculoskeletal	27666822

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFT81 gene.

• not provided (25 variants)
• Short-rib thoracic dysplasia 19 with or without polydactyly (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFT81 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				74	3	77
missense		1	188	2	3	194
nonsense	12	2	2			16
start loss			1			1
frameshift	13		2			15
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	8	1			10
splice region			12	9	2	23
non coding			1	59	17	77
Total	26	11	198	135	23

Highest pathogenic variant AF is 0.0000723

Variants in IFT81

This is a list of pathogenic ClinVar variants found in the IFT81 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-110127382-T-A			Uncertain significance (Oct 21, 2022)
12-110127384-A-G			Uncertain significance (Sep 20, 2021)
12-110127386-T-C			Likely benign (Oct 03, 2021)
12-110127388-A-G		Inborn genetic diseases	Uncertain significance (May 16, 2024)
12-110127389-T-C			Likely benign (Feb 11, 2022)
12-110127405-A-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 15, 2024)
12-110127411-A-C			Uncertain significance (May 05, 2022)
12-110127418-A-G			Uncertain significance (Jan 08, 2024)
12-110127426-C-A			Uncertain significance (Aug 14, 2021)
12-110127431-T-C			Likely benign (Aug 30, 2022)
12-110127444-A-G		Inborn genetic diseases	Uncertain significance (Jun 27, 2022)
12-110127445-A-C		IFT81-related disorder	Likely benign (Jan 31, 2024)
12-110127455-G-A			Likely benign (Mar 10, 2022)
12-110127456-T-C			Uncertain significance (Oct 05, 2022)
12-110127467-G-C		SHORT-RIB THORACIC DYSPLASIA 19 WITHOUT POLYDACTYLY • Short-rib thoracic dysplasia 19 with or without polydactyly	Pathogenic/Likely pathogenic (Aug 11, 2023)
12-110127479-A-G			Likely benign (Dec 30, 2022)
12-110127482-A-G			Likely benign (Jan 13, 2023)
12-110127487-A-G			Uncertain significance (Jun 22, 2023)
12-110127489-G-A			Uncertain significance (Oct 10, 2021)
12-110127497-T-G			Uncertain significance (Aug 08, 2022)
12-110127514-T-C		Short-rib thoracic dysplasia 19 with or without polydactyly	Uncertain significance (Nov 15, 2022)
12-110127523-A-T		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
12-110127530-A-T			Uncertain significance (Nov 15, 2022)
12-110127538-C-G			Likely benign (Oct 17, 2022)
12-110127542-CT-C			Benign (Jan 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFT81	protein_coding	protein_coding	ENST00000242591	18	94463

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.09e-12	0.994	125675	0	73	125748	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.828	293	336	0.873	0.0000173	4496
Missense in Polyphen		79	96.506	0.8186		1278
Synonymous	0.295	99	103	0.963	0.00000467	1132
Loss of Function	2.63	25	43.8	0.571	0.00000246	547

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000842	0.000824
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000170	0.000163
Finnish	0.0000469	0.0000462
European (Non-Finnish)	0.000272	0.000264
Middle Eastern	0.000170	0.000163
South Asian	0.000556	0.000523
Other	0.000168	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the intraflagellar transport (IFT) complex B: together with IFT74, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium. Binds tubulin via its CH (calponin-homology)-like region (PubMed:23990561). Required for ciliogenesis (PubMed:27666822, PubMed:23990561). Required for proper regulation of SHH signaling (PubMed:27666822). {ECO:0000269|PubMed:23990561, ECO:0000269|PubMed:27666822}.
• Disease: DISEASE: Short-rib thoracic dysplasia 19 with or without polydactyly (SRTD19) [MIM:617895]: 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:27666822}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.416
• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.06

Haploinsufficiency Scores

• pHI: 0.220
• hipred: N
• hipred_score: 0.492
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.137

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ift81

Zebrafish Information Network

• Gene name: ift81
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: increased curvature

Gene ontology

• Biological process: spermatogenesis;regulation of smoothened signaling pathway;intraciliary transport involved in cilium assembly;intraciliary transport;cilium assembly
• Cellular component: centrosome;cilium;intraciliary transport particle B;motile cilium;ciliary basal body;sperm midpiece;sperm principal piece;ciliary tip
• Molecular function: protein binding;tubulin binding