IFITM5

interferon induced transmembrane protein 5, the group of Interferon induced transmembrane proteins

Basic information

Region (hg38): 11:298200-299526

Links

ENSG00000206013 ∙ NCBI:387733 ∙ OMIM:614757 ∙ HGNC:16644 ∙ Uniprot:A6NNB3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta type 5 (Definitive), mode of inheritance: AD
• osteogenesis imperfecta type 5 (Strong), mode of inheritance: AD
• osteogenesis imperfecta type 5 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type V	AD	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; Musculoskeletal	10976985; 16162424; 22863190; 22863195; 23408678; 23612438; 23674381; 23813632; 24478195; 24519609
Pamidronate treatment has been described as beneficial in terms of reducing fracture risk, but the advantage of early (genetic) diagnosis is unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IFITM5 gene.

• not_provided (136 variants)
• Inborn_genetic_diseases (38 variants)
• Osteogenesis_imperfecta (9 variants)
• not_specified (9 variants)
• Osteogenesis_imperfecta_type_5 (9 variants)
• IFITM5-related_disorder (7 variants)
• Postmenopausal_osteoporosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IFITM5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001025295.3. 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				23	5	28
missense	1	1	58	28	6	94
nonsense				2		2
start loss						0
frameshift			4	1	1	6
splice donor/acceptor (+/-2bp)						0
Total	1	1	62	54	12

Highest pathogenic variant AF is 7.6590203e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IFITM5	protein_coding	protein_coding	ENST00000382614	2	1327

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000218	0.0862	125318	0	68	125386	0.000271

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.668	94	77.5	1.21	0.00000533	800
Missense in Polyphen		35	25.96	1.3482		296
Synonymous	-0.0763	38	37.4	1.02	0.00000263	288
Loss of Function	-1.32	7	4.11	1.70	3.12e-7	38

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000913	0.0000907
Ashkenazi Jewish	0.00110	0.00110
East Asian	0.000709	0.000707
Finnish	0.00	0.00
European (Non-Finnish)	0.000242	0.000239
Middle Eastern	0.000709	0.000707
South Asian	0.000483	0.000457
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal bone mineralization. {ECO:0000269|PubMed:24519609}.
• Disease: DISEASE: Osteogenesis imperfecta 5 (OI5) [MIM:610967]: An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI5 patients manifest moderate to severe bone fragility, calcification of the forearm interosseous membrane, radial head dislocation, a subphyseal metaphyseal radiodense line, and hyperplastic callus formation. {ECO:0000269|PubMed:22863190, ECO:0000269|PubMed:24519609}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.408
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.51

Haploinsufficiency Scores

• pHI: 0.167
• hipred: N
• hipred_score: 0.282
• ghis: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.146

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ifitm5
• 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); reproductive system phenotype; hematopoietic system phenotype; limbs/digits/tail phenotype; homeostasis/metabolism phenotype; immune system phenotype; skeleton phenotype; growth/size/body region phenotype; craniofacial phenotype; cellular phenotype

Gene ontology

• Biological process: in utero embryonic development;bone mineralization;regulation of bone mineralization;bone morphogenesis
• Cellular component: plasma membrane;integral component of plasma membrane