FKBP8

protein-coding

FKBP prolyl isomerase 8, the group of FKBP prolyl isomerases|Tetratricopeptide repeat domain containing

Gene summary

The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. Unlike the other members of the family, this encoded protein does not seem to have PPIase/rotamase activity. It may have a role in neurons associated with memory function. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012181.5

Inheritance

ClinVar variants

U:50B:3

Top phenotype

Marfanoid habitus and intellectual disability

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:18,531,751-18,544,077

External References & Databases

Ensembl (ENSG00000105701)

Transcript & Mutation Effects

hg38 • Region Span ~12.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spina bifidaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0008449

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FKBP8 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 2

Marfanoid habitus and intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012181.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			49 clinvar	1 clinvar		50
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	50	3	0	53

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 103 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012181.5	RefSeq	NP_036313.3	8	MANE Select
ENST00000608443.6	Ensembl	ENSP00000476767.1	8	MANE Select
NM_001308373.2	RefSeq	NP_001295302.1	8	Standard
ENST00000222308.8	Ensembl	ENSP00000222308.4	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Senescence and Autophagy in Cancer
Post-translational protein modification
Metabolism of proteins
insulin Mam
Ub-specific processing proteases

Biological Process

protein peptidyl-prolyl isomerization
cell fate specification
negative regulation of protein phosphorylation
apoptotic process
smoothened signaling pathway

Molecular Function

peptidyl-prolyl cis-trans isomerase activity
protein binding
identical protein binding
metal ion binding
disordered domain specific binding

Cellular Component

mitochondrion
endoplasmic reticulum
cytosol
membrane
integral component of endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000608443
Coding exons: 8
Length: 12327
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125717
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.33	166	275	0.605	0.0000186	2642
Missense (PolyPhen)		23	69.368	0.33156		758
Synonymous	-0.207	132	129	1.02	0.00000989	868
Loss of Function	3.99	0	18.5	0.00	8.76e-7	210

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis. {ECO:0000269|PubMed:12510191, ECO:0000269|PubMed:15757646, ECO:0000269|PubMed:16176796}.;

Recessive Scores

pRec: 0.162

Intolerance Scores

LoFtool: 0.0296
RVIS EVS: -0.58
RVIS percentile EVS: 18.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.937

Gene Damage Prediction

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