IFT74

intraflagellar transport 74, the group of IFT-B1 complex

Basic information

Region (hg38): 9:26947039-27066134

Previous symbols: [ "CCDC2" ]

Links

ENSG00000096872 ∙ NCBI:80173 ∙ OMIM:608040 ∙ HGNC:21424 ∙ Uniprot:Q96LB3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 22 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 22 (Limited), mode of inheritance: AR
• spermatogenic failure 58 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 22	AR	Endocrine	Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	27486776; 33531668; 33689014; 34539760; 36356613

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFT74 gene.

• not_provided (451 variants)
• IFT74-related_disorder (182 variants)
• Inborn_genetic_diseases (88 variants)
• not_specified (54 variants)
• Joubert_syndrome_40 (12 variants)
• Bardet-Biedl_syndrome_22 (10 variants)
• Spermatogenic_failure_58 (3 variants)
• Optic_atrophy (2 variants)
• Microcephaly (2 variants)
• Retinal_dystrophy (2 variants)
• Jeune_thoracic_dystrophy (2 variants)
• Multiple_Morphological_Anomalies_of_Sperm_Flagella_(MMAF) (1 variants)
• Joubert_syndrome (1 variants)
• Short-rib_thoracic_dysplasia_6_with_or_without_polydactyly (1 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 IFT74 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000025103.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	4	106	4	115
missense	1	2	239	7	2	251
nonsense	19	4				23
start loss		1	1			2
frameshift	12	1	1			14
splice donor/acceptor (+/-2bp)	1	11	2			14
Total	33	20	247	113	6

Highest pathogenic variant AF is 0.000176046

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFT74	protein_coding	protein_coding	ENST00000443698	19	115892

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.72e-13	0.943	124637	0	157	124794	0.000629

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.07	348	296	1.17	0.0000144	3989
Missense in Polyphen		67	59.107	1.1335		791
Synonymous	-0.299	97	93.3	1.04	0.00000447	990
Loss of Function	2.17	26	41.0	0.634	0.00000212	507

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000905	0.000886
Ashkenazi Jewish	0.000304	0.000298
East Asian	0.000229	0.000223
Finnish	0.000140	0.000139
European (Non-Finnish)	0.00107	0.00106
Middle Eastern	0.000229	0.000223
South Asian	0.000101	0.0000980
Other	0.000501	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the intraflagellar transport (IFT) complex B: together with IFT81, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium. Binds beta-tubulin via its basic region. Required for ciliogenesis. {ECO:0000269|PubMed:23990561}.
• Pathway: Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.0851

Intolerance Scores

• loftool: 0.962
• rvis_EVS: 1.2
• rvis_percentile_EVS: 92.98

Haploinsufficiency Scores

• pHI: 0.287
• hipred: N
• hipred_score: 0.425
• ghis: 0.459

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.164

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ift74
• Phenotype: growth/size/body region phenotype; respiratory system 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)

Zebrafish Information Network

• Gene name: ift74
• Affected structure: pronephric proximal convoluted tubule
• Phenotype tag: abnormal
• Phenotype quality: increased diameter

Gene ontology

• Biological process: keratinocyte development;Notch signaling pathway;determination of left/right symmetry;heart development;positive regulation of cell adhesion mediated by integrin;intraciliary transport involved in cilium assembly;positive regulation of transcription by RNA polymerase II;negative regulation of epithelial cell proliferation;cilium assembly;non-motile cilium assembly
• Cellular component: nucleus;centrosome;cilium;intraciliary transport particle B;cytoplasmic vesicle;motile cilium;ciliary tip
• Molecular function: chromatin binding;protein binding;beta-tubulin binding