FNIP2

protein-coding

folliculin interacting protein 2, the group of DENN domain containing

Gene summary

This gene encodes a protein that binds to the tumor suppressor folliculin and to AMP-activated protein kinase (AMPK), and may play a role cellular metabolism and nutrient sensing by regulating the AMPK-mechanistic target of rapamycin signaling pathway. The encoded protein may also be involved in regulating the O6-methylguanine-induced apoptosis signaling pathway. This gene has a closely related paralog that encodes a protein with similar binding activities. Both related proteins also associate with the molecular chaperone heat shock protein-90 (Hsp90) and negatively regulate its ATPase activity and facilitate its association with folliculin. [provided by RefSeq, Jul 2017]

MANE transcript

NM_020840.3

Inheritance

—

ClinVar variants

U:129B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr4:158,769,026-158,908,050

External References & Databases

Ensembl (ENSG00000052795)

Transcript & Mutation Effects

hg38 • Region Span ~139.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FNIP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 129

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020840.3. 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			1 clinvar	2 clinvar	1 clinvar	4
missense			124 clinvar	10 clinvar	1 clinvar	135
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	129	12	2	143

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020840.3	RefSeq	NP_065891.1	17	MANE Select
ENST00000264433.11	Ensembl	ENSP00000264433.6	17	MANE Select
NM_001323916.2	RefSeq	NP_001310845.1	17	Standard
NM_001346043.2	RefSeq	NP_001332972.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mTOR signaling pathway - Homo sapiens (human)

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of protein phosphorylation
protein phosphorylation
mitochondrion organization
intrinsic apoptotic signaling pathway in response to DNA damage

Molecular Function

protein binding
ATPase inhibitor activity
chaperone binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264433
Coding exons: 17
Length: 138912
Individuals with no LoFs: 124633
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 124640
p: 0.0000281

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.28	517	606	0.854	0.0000325	7303
Missense (PolyPhen)		106	180.39	0.58761		2202
Synonymous	0.653	213	225	0.945	0.0000128	2178
Loss of Function	6.18	2	48.5	0.0413	0.00000255	581

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000027	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a co-chaperone of HSP90AA1. Inhibits the ATPase activity of HSP90AA1 leading to reduction in its chaperone activity. Facilitates the binding of client protein FLCN to HSP90AA1 (PubMed:27353360). May play a role in the signal transduction pathway of apoptosis induced by O6-methylguanine- mispaired lesions (By similarity). May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways (PubMed:18403135). May regulate phosphorylation of RPS6KB1 (PubMed:18663353). {ECO:0000250|UniProtKB:Q80TD3, ECO:0000269|PubMed:18403135, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:27353360}.;

Recessive Scores

pRec: 0.0828

Intolerance Scores

LoFtool: 0.243
RVIS EVS: -0.1
RVIS percentile EVS: 45.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.175

Gene Damage Prediction

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