FKBP6

FKBP prolyl isomerase family member 6 (inactive), the group of FKBP prolyl isomerases

Basic information

Region (hg38): 7:73328161-73358637

Links

ENSG00000077800 ∙ NCBI:8468 ∙ OMIM:604839 ∙ HGNC:3722 ∙ Uniprot:O75344 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 77 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 77	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	Genitourinary	36150389

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FKBP6 gene.

• Male infertility (2 variants)
• Spermatogenic failure 77 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FKBP6 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			17	2	1	20
nonsense		2				2
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region				1	1	2
non coding						0
Total	2	3	17	3	1

Highest pathogenic variant AF is 0.000191

Variants in FKBP6

This is a list of pathogenic ClinVar variants found in the FKBP6 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-73328448-A-C		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
7-73328471-G-A		Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
7-73328618-G-A			Uncertain significance (Apr 27, 2019)
7-73329440-C-A		Inborn genetic diseases	Uncertain significance (May 23, 2024)
7-73330159-T-A		Inborn genetic diseases	Uncertain significance (Sep 26, 2022)
7-73330211-G-C		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
7-73330237-A-G		Inborn genetic diseases	Uncertain significance (May 30, 2023)
7-73330268-C-T			Likely benign (Aug 01, 2022)
7-73330276-C-G		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
7-73330342-C-T		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
7-73331655-A-T		Spermatogenic failure 77 • Male infertility	Likely pathogenic (May 12, 2022)
7-73331676-C-T		Inborn genetic diseases	Uncertain significance (Nov 05, 2021)
7-73331696-G-A		Inborn genetic diseases	Uncertain significance (Jan 10, 2022)
7-73331695-A-AGTGGCAGCTACGGAACGGGAGT		Spermatogenic failure 77 • Male infertility	Pathogenic (May 12, 2022)
7-73331711-C-T		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
7-73331735-C-T			Likely benign (Mar 01, 2024)
7-73331745-G-A		Inborn genetic diseases	Uncertain significance (Oct 05, 2022)
7-73331751-A-G		Inborn genetic diseases	Likely benign (Jan 03, 2024)
7-73331778-T-TGA		FKBP6-related disorder	Likely benign (Apr 03, 2019)
7-73340636-A-G		Spermatogenic failure 77 • Male infertility	Pathogenic (May 12, 2022)
7-73340654-G-A		FKBP6-related disorder	Benign (May 01, 2019)
7-73340659-C-T		Spermatogenic failure 77 • Male infertility	Likely pathogenic (May 12, 2022)
7-73340685-C-A		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
7-73340723-T-G		Inborn genetic diseases	Uncertain significance (Jun 05, 2023)
7-73341321-C-T		Male infertility • Spermatogenic failure 77	Likely pathogenic (May 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FKBP6	protein_coding	protein_coding	ENST00000252037	8	30468

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000140	0.847	125675	0	73	125748	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.666	154	179	0.860	0.0000112	2098
Missense in Polyphen		45	58.903	0.76396		707
Synonymous	0.773	66	74.5	0.886	0.00000459	658
Loss of Function	1.46	12	18.9	0.636	0.00000111	213

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000390	0.000387
Ashkenazi Jewish	0.00	0.00
East Asian	0.000387	0.000381
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000450	0.000448
Middle Eastern	0.000387	0.000381
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Co-chaperone required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Acts as a co-chaperone via its interaction with HSP90 and is required for the piRNA amplification process, the secondary piRNA biogenesis. May be required together with HSP90 in removal of 16 nucleotide ping-pong by-products from Piwi complexes, possibly facilitating turnover of Piwi complexes (By similarity). {ECO:0000250}.
• Disease: DISEASE: Note=Defects in FKBP6 may be a cause of azoospermia. A study based on 323 patients with azoospermia or severe oligozoospermia suggested an association between FKBP6 variants and azoospermia (PubMed:17307919). However, other studies suggest that defects in FKBP6 are not a common cause of non-obstructive azoospermia (PubMed:16227348). {ECO:0000269|PubMed:16227348, ECO:0000269|PubMed:17307919}.

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.637
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.21

Haploinsufficiency Scores

• pHI: 0.106
• hipred: Y
• hipred_score: 0.735

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.531

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fkbp6
• Phenotype: endocrine/exocrine gland phenotype; reproductive system phenotype

Gene ontology

• Biological process: protein peptidyl-prolyl isomerization;protein folding;spermatogenesis;cell differentiation;gene silencing by RNA;piRNA metabolic process;DNA methylation involved in gamete generation;positive regulation of viral genome replication;meiotic cell cycle
• Cellular component: synaptonemal complex;cytoplasm;cytosol
• Molecular function: peptidyl-prolyl cis-trans isomerase activity;protein binding;FK506 binding;identical protein binding;Hsp90 protein binding