IFT27

intraflagellar transport 27, the group of IFT-B1 complex|RAB like GTPases

Basic information

Region (hg38): 22:36758201-36776256

Previous symbols: [ "RABL4" ]

Links

ENSG00000100360 ∙ NCBI:11020 ∙ OMIM:615870 ∙ HGNC:18626 ∙ Uniprot:Q9BW83 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bardet-Biedl syndrome 19 (Limited), mode of inheritance: AR
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 19 (Limited), mode of inheritance: AR
• Bardet-Biedl syndrome 19 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 19	AR	Endocrine	Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	24488770; 36356613

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFT27 gene.

• not provided (7 variants)
• Bardet-Biedl syndrome 19 (3 variants)
• Bardet-Biedl syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFT27 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				29	2	31
missense	2		52	3	2	59
nonsense	3		2			5
start loss						0
frameshift	4					4
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			8	6	1	15
non coding				23	3	26
Total	9	2	54	55	7

Highest pathogenic variant AF is 0.0000394

Variants in IFT27

This is a list of pathogenic ClinVar variants found in the IFT27 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-36758309-C-T		IFT27-related disorder	Likely benign (Nov 12, 2019)
22-36758314-T-C			Likely benign (Apr 14, 2023)
22-36758314-T-G			Likely benign (Jun 20, 2022)
22-36758315-G-T			Uncertain significance (Jul 07, 2023)
22-36758321-G-C			Uncertain significance (Jul 19, 2022)
22-36758324-C-T		Inborn genetic diseases	Likely benign (Jan 13, 2024)
22-36758325-G-A		Inborn genetic diseases • IFT27-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
22-36758345-C-T		IFT27-related disorder	Uncertain significance (Feb 08, 2024)
22-36758346-G-A			Uncertain significance (Jul 02, 2022)
22-36758350-C-T			Likely benign (Apr 20, 2020)
22-36758362-C-T			Likely benign (Aug 01, 2022)
22-36758363-T-A			Uncertain significance (Sep 01, 2021)
22-36758369-G-A		Inborn genetic diseases • IFT27-related disorder	Conflicting classifications of pathogenicity (Dec 05, 2023)
22-36758374-G-T		IFT27-related disorder	Uncertain significance (Dec 22, 2022)
22-36758385-G-A			Uncertain significance (Nov 16, 2022)
22-36758391-C-T		IFT27-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 12, 2024)
22-36758392-G-A		IFT27-related disorder	Likely benign (Nov 27, 2023)
22-36758406-C-A			Uncertain significance (Dec 11, 2019)
22-36758407-T-C		IFT27-related disorder	Conflicting classifications of pathogenicity (Apr 26, 2023)
22-36758419-CAGTTTAAA-C			Likely benign (Dec 07, 2023)
22-36758422-T-G			Likely benign (Jun 26, 2022)
22-36762889-A-G			Likely benign (Jan 20, 2024)
22-36762890-G-A			Likely benign (Aug 16, 2022)
22-36762906-C-T			Uncertain significance (Jun 23, 2022)
22-36762907-G-A		IFT27-related disorder	Likely benign (May 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFT27	protein_coding	protein_coding	ENST00000433985	7	18055

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000588	0.463	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.216	98	104	0.940	0.00000586	1201
Missense in Polyphen		28	36.506	0.767		483
Synonymous	0.727	37	43.1	0.859	0.00000247	361
Loss of Function	0.582	9	11.1	0.811	5.69e-7	127

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000149	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000288	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000309	0.000308
Middle Eastern	0.000288	0.000272
South Asian	0.0000366	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Small GTPase-like component of the intraflagellar transport (IFT) complex B that promotes the exit of the BBSome complex from cilia via its interaction with ARL6 (PubMed:25443296). Not involved in entry of the BBSome complex into cilium. Prevents aggregation of GTP-free ARL6 (PubMed:25443296). Required for hedgehog signaling. Forms a subcomplex within the IFT complex B with IFT25. Its role in intraflagellar transport is mainly seen in tissues rich in ciliated cells such as kidney and testis. Essential for male fertility, spermiogenesis and sperm flagella formation. Plays a role in the early development of the kidney. May be involved in the regulation of ureteric bud initiation (By similarity). {ECO:0000250|UniProtKB:A8HN58, ECO:0000269|PubMed:25443296}.
• Disease: DISEASE: Bardet-Biedl syndrome 19 (BBS19) [MIM:615996]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:24488770}. 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: 0.0812

Intolerance Scores

• rvis_EVS: 0.39
• rvis_percentile_EVS: 76.05

Haploinsufficiency Scores

• pHI: 0.0316
• hipred: N
• hipred_score: 0.251
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.860

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ift27
• Phenotype: skeleton phenotype; vision/eye phenotype; digestive/alimentary 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; 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; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: ift27
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: curved ventral

Gene ontology

• Biological process: kidney development;intracellular protein transport;smoothened signaling pathway;spermatogenesis;Rab protein signal transduction;intraciliary transport involved in cilium assembly;intraciliary transport;inner ear receptor cell stereocilium organization;cochlea development
• Cellular component: cytoplasm;centrosome;cilium;intraciliary transport particle B;motile cilium;sperm flagellum;sperm midpiece;sperm principal piece;ciliary tip
• Molecular function: GTPase activity;protein binding;GTP binding