FKBP10

FKBP prolyl isomerase 10, the group of EF-hand domain containing|FKBP prolyl isomerases

Basic information

Region (hg38): 17:41812680-41823213

Links

ENSG00000141756

∙ NCBI:60681 ∙ OMIM:607063 ∙ HGNC:18169 ∙ Uniprot:Q96AY3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

osteogenesis imperfecta type 11 (Definitive), mode of inheritance: AR
osteogenesis imperfecta type 11 (Strong), mode of inheritance: AR
Bruck syndrome (Supportive), mode of inheritance: AR
arthrogryposis-like syndrome (Supportive), mode of inheritance: AR
osteogenesis imperfecta type 3 (Supportive), mode of inheritance: AD
osteogenesis imperfecta type 4 (Supportive), mode of inheritance: AD
Bruck syndrome 1 (Strong), mode of inheritance: AR
osteogenesis imperfecta type 11 (Strong), mode of inheritance: AR
Bruck syndrome 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type XI; Bruck syndrome 1	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	Dental; Musculoskeletal	20362275; 20696291; 20839288; 21567934
Bisphosphonates may reduce fracture frequency, but it is unclear if early (genomic) diagnosis would be additionally beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FKBP10 gene.

not_provided (489 variants)
Inborn_genetic_diseases (92 variants)
Osteogenesis_imperfecta_type_11 (88 variants)
Bruck_syndrome_1 (32 variants)
not_specified (27 variants)
Osteogenesis_imperfecta (26 variants)
FKBP10-related_disorder (24 variants)
Osteogenesis_imperfecta_type_12 (6 variants)
Osteogenesis_imperfecta_type_III (4 variants)
Osteogenesis_Imperfecta,_Recessive (2 variants)
Bruck_syndrome (1 variants)
Abnormality_of_the_skeletal_system (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FKBP10 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021939.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	194 clinvar	4 clinvar	201
missense	1 clinvar	9 clinvar	180 clinvar	9 clinvar		199
nonsense	7 clinvar	3 clinvar				10
start loss	1					1
frameshift	26 clinvar	12 clinvar				38
splice donor/acceptor (+/-2bp)	3 clinvar	9 clinvar		1 clinvar		13
Total	38	33	183	204	4

Highest pathogenic variant AF is 0.00009669921

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FKBP10	protein_coding	protein_coding	ENST00000321562	10	10534

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000238	0.980	125670	0	78	125748	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.713	322	360	0.894	0.0000239	3769
Missense in Polyphen		128	158.51	0.80752		1677
Synonymous	-1.04	177	160	1.10	0.0000115	1207
Loss of Function	2.13	13	24.3	0.535	0.00000139	259

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000915	0.000908
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000382	0.000381
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000330	0.000316
Middle Eastern	0.000382	0.000381
South Asian	0.000200	0.000196
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: PPIases accelerate the folding of proteins during protein synthesis.;
Disease: DISEASE: Osteogenesis imperfecta 11 (OI11) [MIM:610968]: A 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. OI11 is an autosomal recessive form. {ECO:0000269|PubMed:20362275, ECO:0000269|PubMed:20839288, ECO:0000269|PubMed:22949511}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bruck syndrome 1 (BRKS1) [MIM:259450]: A disease characterized by generalized osteopenia, congenital joint contractures, fragile bones with onset of fractures in infancy or early childhood, short stature, severe limb deformity, progressive scoliosis, and pterygia. {ECO:0000269|PubMed:20839288, ECO:0000269|PubMed:22949511}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.108

Intolerance Scores

loftool: 0.337
rvis_EVS: -0.75
rvis_percentile_EVS: 13.71

Haploinsufficiency Scores

pHI: 0.446
hipred: N
hipred_score: 0.443
ghis: 0.563

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.722

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Fkbp10
Phenotype: craniofacial phenotype; cellular phenotype; homeostasis/metabolism 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); hematopoietic 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); growth/size/body region 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; skeleton phenotype; embryo phenotype;

Gene ontology

Biological process: protein peptidyl-prolyl isomerization
Cellular component: endoplasmic reticulum lumen
Molecular function: peptidyl-prolyl cis-trans isomerase activity;calcium ion binding;FK506 binding