FKBP4

FKBP prolyl isomerase 4, the group of FKBP prolyl isomerases|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 12:2794970-2805423

Links

ENSG00000004478 ∙ NCBI:2288 ∙ OMIM:600611 ∙ HGNC:3720 ∙ Uniprot:Q02790 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FKBP4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FKBP4 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					1	1
missense			20	3	2	25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	20	3	3

Variants in FKBP4

This is a list of pathogenic ClinVar variants found in the FKBP4 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-2797166-A-C			Likely benign (Jul 06, 2018)
12-2799114-A-C			Benign (Jul 04, 2018)
12-2799139-G-A			Likely benign (Aug 15, 2018)
12-2799148-T-C		not specified	Uncertain significance (Sep 22, 2023)
12-2799201-C-T		not specified	Uncertain significance (Oct 06, 2021)
12-2799202-G-A		not specified	Uncertain significance (Sep 20, 2023)
12-2799228-G-A		not specified	Uncertain significance (Sep 22, 2023)
12-2799228-G-T		not specified	Uncertain significance (Dec 21, 2022)
12-2799861-G-A		not specified	Uncertain significance (Mar 29, 2024)
12-2799869-G-T		not specified	Uncertain significance (Sep 27, 2022)
12-2800035-G-A			Benign (Mar 29, 2018)
12-2800115-A-C		not specified	Uncertain significance (Jan 16, 2024)
12-2800395-G-A		not specified	Uncertain significance (Jun 28, 2022)
12-2800468-A-G		not specified	Likely benign (Nov 17, 2022)
12-2800524-A-T		not specified	Uncertain significance (Mar 31, 2024)
12-2800561-T-C		not specified	Uncertain significance (Jan 09, 2024)
12-2800572-A-G		not specified	Uncertain significance (May 26, 2022)
12-2801137-C-A		not specified	Uncertain significance (Aug 14, 2023)
12-2801224-G-A			Benign (Jul 04, 2018)
12-2801253-A-G		not specified	Uncertain significance (Nov 20, 2023)
12-2801267-G-A		not specified	Uncertain significance (Jan 20, 2023)
12-2801279-C-T		not specified	Uncertain significance (Jan 02, 2024)
12-2801301-G-A		not specified	Uncertain significance (Oct 29, 2021)
12-2801350-G-C		not specified	Uncertain significance (May 02, 2024)
12-2803151-G-T		not specified	Uncertain significance (May 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FKBP4	protein_coding	protein_coding	ENST00000001008	10	10458

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.155	0.844	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.21	197	251	0.785	0.0000140	3001
Missense in Polyphen		67	98.929	0.67725		1147
Synonymous	-1.06	109	95.8	1.14	0.00000522	853
Loss of Function	3.34	6	23.5	0.256	0.00000124	280

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000881	0.0000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria. {ECO:0000269|PubMed:1279700, ECO:0000269|PubMed:1376003, ECO:0000269|PubMed:19945390, ECO:0000269|PubMed:21730050, ECO:0000269|PubMed:2378870}.
• Pathway: Estrogen signaling pathway - Homo sapiens (human);Glucocorticoid Pathway (Peripheral Tissue), Pharmacodynamics;Androgen receptor signaling pathway;Cellular response to heat stress;Signal Transduction;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;Regulation of HSF1-mediated heat shock response;HSP90 chaperone cycle for steroid hormone receptors (SHR);Cellular responses to stress;Cellular responses to external stimuli;Glucocorticoid receptor regulatory network;Coregulation of Androgen receptor activity;Cellular response to heat stress;Signaling by Nuclear Receptors;ESR-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.187

Intolerance Scores

• loftool: 0.191
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.15

Haploinsufficiency Scores

• pHI: 0.218
• hipred: Y
• hipred_score: 0.825
• ghis: 0.408

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.858

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fkbp4
• Phenotype: embryo phenotype; reproductive system 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); digestive/alimentary phenotype; renal/urinary system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: fkbp4
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: protein peptidyl-prolyl isomerization;protein folding;steroid hormone receptor complex assembly;copper ion transport;embryo implantation;negative regulation of neuron projection development;androgen receptor signaling pathway;prostate gland development;negative regulation of microtubule polymerization or depolymerization;negative regulation of microtubule polymerization;protein-containing complex localization;male sex differentiation;chaperone-mediated protein folding;regulation of cellular response to heat
• Cellular component: nucleoplasm;cytoplasm;mitochondrion;cytosol;microtubule;protein-containing complex;neuronal cell body;axonal growth cone;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: RNA binding;peptidyl-prolyl cis-trans isomerase activity;protein binding;ATP binding;GTP binding;FK506 binding;protein binding, bridging;heat shock protein binding;copper-dependent protein binding;glucocorticoid receptor binding;tau protein binding;phosphoprotein binding