FKBP14

FKBP prolyl isomerase 14, the group of FKBP prolyl isomerases|EF-hand domain containing

Basic information

Region (hg38): 7:30010586-30026702

Links

ENSG00000106080 ∙ NCBI:55033 ∙ OMIM:614505 ∙ HGNC:18625 ∙ Uniprot:Q9NWM8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ehlers-Danlos syndrome, kyphoscoliotic and deafness type (Definitive), mode of inheritance: AR
• Ehlers-Danlos syndrome, kyphoscoliotic and deafness type (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, kyphoscoliotic and deafness type (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, kyphoscoliotic and deafness type (Moderate), mode of inheritance: AR
• Ehlers-Danlos syndrome, kyphoscoliotic and deafness type (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, kyphoscoliotic and deafness type (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ehlers-Danlos syndrome, kyphoscoliotic type, 2	AR	Cardiovascular	Cardiovascular complications, including aortic rupture, have been described, and awareness and surveillance may allow rapid diagnosis and treatment, which may ameliorate morbidity and mortality	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Genitourinary; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	22265013; 24773188

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FKBP14 gene.

• Ehlers-Danlos syndrome, kyphoscoliotic and deafness type (146 variants)
• Cardiovascular phenotype (58 variants)
• not provided (38 variants)
• Ehlers-Danlos syndrome (7 variants)
• not specified (7 variants)
• Inborn genetic diseases (7 variants)
• Hypotonia (1 variants)
• Joint hypermobility;Pes valgus;Thoracolumbar scoliosis;Hypotonia;Congenital muscular dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FKBP14 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				37	1	38
missense			84	1		85
nonsense	2	1	2			5
start loss						0
frameshift	3	4				7
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)		1	2			3
splice region			3	8		11
non coding				23	6	29
Total	5	6	89	62	7

Highest pathogenic variant AF is 0.00000657

Variants in FKBP14

This is a list of pathogenic ClinVar variants found in the FKBP14 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-30014063-G-A		not specified	Benign (Mar 29, 2016)
7-30014733-C-G			Likely benign (Oct 21, 2020)
7-30014735-C-G		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Pathogenic (Aug 07, 2019)
7-30014739-A-G		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Uncertain significance (May 19, 2022)
7-30014747-G-A		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Likely benign (Oct 13, 2021)
7-30014752-T-G		Ehlers-Danlos syndrome, kyphoscoliotic type, 2 • Cardiovascular phenotype	Uncertain significance (Jan 25, 2023)
7-30014756-T-C		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Likely benign (Apr 02, 2023)
7-30014776-T-C		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Uncertain significance (Mar 18, 2022)
7-30014780-C-A		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Likely benign (Apr 12, 2022)
7-30014782-C-T		Ehlers-Danlos syndrome, kyphoscoliotic type, 2 • Cardiovascular phenotype	Uncertain significance (Jan 04, 2023)
7-30014789-G-A		Cardiovascular phenotype	Likely benign (Dec 08, 2023)
7-30014789-G-C		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Uncertain significance (May 24, 2019)
7-30014791-C-T		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Uncertain significance (Nov 28, 2022)
7-30014795-A-G		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Likely benign (Dec 01, 2023)
7-30014795-ATCT-A		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Pathogenic (Jan 15, 2019)
7-30014798-T-A		Ehlers-Danlos syndrome, kyphoscoliotic type, 2 • Cardiovascular phenotype	Uncertain significance (Jun 20, 2022)
7-30014800-CTTT-C		Ehlers-Danlos syndrome, kyphoscoliotic type, 2 • Ehlers-Danlos syndrome • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jan 04, 2024)
7-30014801-T-C		Cardiovascular phenotype	Likely benign (Feb 28, 2023)
7-30014803-T-A			Uncertain significance (Jun 23, 2020)
7-30014803-T-G		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Uncertain significance (Aug 27, 2021)
7-30014810-A-T		Ehlers-Danlos syndrome, kyphoscoliotic type, 2 • Cardiovascular phenotype	Likely benign (Aug 02, 2021)
7-30014811-A-C		Ehlers-Danlos syndrome, kyphoscoliotic type, 2 • Cardiovascular phenotype	Uncertain significance (May 11, 2023)
7-30014813-A-G		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Likely benign (Aug 09, 2022)
7-30014814-T-C		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Uncertain significance (Nov 15, 2022)
7-30014815-C-A		Ehlers-Danlos syndrome, kyphoscoliotic type, 2	Uncertain significance (Mar 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FKBP14	protein_coding	protein_coding	ENST00000222803	4	16098

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000152	0.240	125605	0	143	125748	0.000569

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0939	105	108	0.975	0.00000479	1404
Missense in Polyphen		40	46.869	0.85344		607
Synonymous	0.782	33	39.2	0.841	0.00000189	371
Loss of Function	0.0702	9	9.23	0.975	4.60e-7	122

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000546	0.000541
Ashkenazi Jewish	0.00	0.00
East Asian	0.000165	0.000163
Finnish	0.000287	0.000277
European (Non-Finnish)	0.00111	0.000985
Middle Eastern	0.000165	0.000163
South Asian	0.000241	0.000229
Other	0.000409	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: PPIase which accelerates the folding of proteins during protein synthesis. Has a preference for substrates containing 4- hydroxylproline modifications, including type III collagen. May also target type VI and type X collagens. {ECO:0000269|PubMed:24821723}.
• Disease: DISEASE: Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (EDSKSCL2) [MIM:614557]: A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSKSCL2 is an autosomal recessive form characterized by severe generalized hypotonia at birth, myopathy, early-onset progressive kyphoscoliosis, joint hypermobility without contractures, hyperelastic skin with follicular hyperkeratosis, easy bruising, and occasional abnormal scarring, sensorineural hearing impairment, and normal pyridinoline excretion in urine. {ECO:0000269|PubMed:22265013}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: XBP1(S) activates chaperone genes (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.751
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.64

Haploinsufficiency Scores

• pHI: 0.171
• hipred: N
• hipred_score: 0.389
• ghis: 0.561

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.949

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fkbp14

Gene ontology

• Biological process: protein peptidyl-prolyl isomerization;IRE1-mediated unfolded protein response
• Cellular component: endoplasmic reticulum lumen
• Molecular function: peptidyl-prolyl cis-trans isomerase activity;calcium ion binding