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.

Inborn_genetic_diseases (39 variants)
Spermatogenic_failure_77 (5 variants)
Male_infertility (5 variants)
not_provided (4 variants)
FKBP6-related_disorder (3 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. These statistics are base on transcript: NM_000003602.5. 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				1 clinvar		1
missense			38 clinvar	3 clinvar	1 clinvar	42
nonsense		2 clinvar				2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar				2
Total	2	3	38	4	1

Highest pathogenic variant AF is 0.000229878

Loading clinvar variants...

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
ghis

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