GeneBe

IFT27

protein-coding

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

Gene summary

This gene encodes a GTP-binding protein that is a core component of the intraflagellar transport complex B. Characterization of the similar Chlamydomonas protein indicates a function in cell cycle control. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

Previous symbols:
  • RABL4

MANE transcript

NM_001177701.3

Inheritance

AR

ClinVar variants

P:16U:88B:56

Top phenotype

Bardet-Biedl syndrome 19

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr22:36,758,202-36,776,256

External References & Databases

Ensembl (ENSG00000100360)NCBI Gene (11020)OMIM (615870)HGNC:18626GenCCUniProt (Q9BW83)AlphaFoldClinVar (IFT27)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~18.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Bardet-Biedl syndrome 19LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014447

Submitter: Ambry Genetics

ciliopathyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0005308

Submitter: ClinGen

The *IFT27* gene is located in chromosome 22q12.3 and encodes the intraflagellar transport (IFT) 27 protein, a small GTPase within IFT complex-B. The protein has a regulatory role in the trafficking of proteins via the Bardet-Biedl Syndrome (BBS) complex (BBsome) into and out of cilia and it is also required for hedgehog signaling. It is ubiquitously expressed at varying levels in all tissues. *IFT27* was first reported in relation to BBS in 2014 (Aldahmesh et al., PMID: 24488770). The mechanism of pathogenicity appears to be loss of function. Patients with biallelic *IFT27* pathogenic variants presented with clinical features consistent with ciliopathies, including neurodevelopmental delay, retinitis pigmentosa, kidney disease, obesity, genital anomalies, and polydactyly. At least 6 variants (missense, nonsense, frameshift, splice site) have been reported in five probands in five publications (PMIDs: 24488770, 29704304, 29588463, 30761183, 37239474) are included in this curation. The majority of the variants were loss of function. Functional data supports the pathogenicity of a missense variant and a splice site variant (PMIDs: 24488770, 30761183). A total of 7.1 pts. for genetic evidence was reached. This gene-disease relationship is also supported by functional studies, expression studies, in vitro assays in non-patient cells, and animal models. Knockout zebrafish model showed typical ciliopathy phenotypes, like laterality defects, body curvature, and cystic kidneys (PMID: 24488770) and knockout mice displayed facial dysmorphism, abnormal palate development, spinal curvature, an abnormal rib cage, congenital heart disease, and various digit defects including polydactyly (PMID: 25446516). BBSome subunits and regulators cannot exit the cilia and instead accumulate in knockout mouse embryonic fibroblasts (PMID: 25446516, 25443296). More evidence is available in the literature, but the maximum score for experimental evidence (6 pts.) was reached. In summary, there is definitive evidence supporting the relationship for *IFT27* that we are terming autosomal recessive ciliopathy-*IFT27*. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Kidney Cystic and Ciliopathy Disorders Expert Panel GCEP on the meeting date [February 10, 2025] (SOP Version 11).

Bardet-Biedl syndrome 19LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014447

Submitter: G2P

Bardet-Biedl syndrome 19STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014447

Submitter: PanelApp Australia

Bardet-Biedl syndrome 19STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014447

Submitter: Labcorp Genetics (formerly Invitae)

Bardet-Biedl syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015229

Submitter: Orphanet

Clinical Genomic Database (CGD)

Bardet-Biedl syndrome 19AR

Manifestation: Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal

Intervention: Endocrine

Rationale: Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial

Refs: 24488770; 36356613Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IFT27 variants in ClinVar

10 Conditions Cataloged
not providedTotal: 171
IFT27-related disorderTotal: 77
Inborn genetic diseasesTotal: 28
not specifiedTotal: 24
Bardet-Biedl syndrome 19Total: 10
IFT27-related disordersTotal: 4
Bardet-Biedl syndromeTotal: 3
Jeune thoracic dystrophyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001177701.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
43
clinvar
 46
missense
2
clinvar
2
clinvar
77
clinvar
11
clinvar
2
clinvar
 94
nonsense
1
clinvar
3
clinvar
2
clinvar
 6
start loss
0
frameshift
2
clinvar
2
clinvar
2
clinvar
 6
splice donor/acceptor (+/-2bp)
4
clinvar
4
clinvar
 8
Total51188542160

Highest pathogenic variant AF is 0.00006537299

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001177701.3RefSeqNP_001171172.17MANE Select
ENST00000433985.7EnsemblENSP00000393541.27MANE Select
NM_001363003.2RefSeqNP_001349932.17Standard
NM_006860.5RefSeqNP_006851.17Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
ift27Danio rerio

Structure: trunk

Quality: curved ventral

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Intraflagellar transport
  • Cilium Assembly
  • Organelle biogenesis and maintenance

Biological Process

  • kidney development
  • intracellular protein transport
  • smoothened signaling pathway
  • spermatogenesis
  • Rab protein signal transduction

Molecular Function

  • GTPase activity
  • protein binding
  • GTP binding

Cellular Component

  • cytoplasm
  • centrosome
  • cilium
  • intraciliary transport particle B
  • motile cilium

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000433985
Coding exons
7
Length
18055
Individuals with no LoFs
125702
Homozygous LoFs
0
Heterozygous LoFs
46
Defined
125748
p
0.000183
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.216981040.9400.000005861201
Missense (PolyPhen)2836.5060.767483
Synonymous0.7273743.10.8590.00000247361
Loss of Function0.582911.10.8115.69e-7127

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000870.000087rare
Ashkenazi Jewish00.0absent
East Asian0.000290.00027rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000310.00031rare
South Asian0.0000370.000033rare
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.0812

Intolerance Scores

RVIS EVS
0.39
RVIS percentile EVS
76.05

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.860

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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