FNIP1

folliculin interacting protein 1, the group of DENN domain containing

Basic information

Region (hg38): 5:131641713-131797017

Links

ENSG00000217128 ∙ NCBI:96459 ∙ OMIM:610594 ∙ HGNC:29418 ∙ Uniprot:Q8TF40 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 93 and hypertrophic cardiomyopathy (Strong), mode of inheritance: AR
• FNIP1-associated syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 93 and hypertrophic cardiomyopath	AR	Allergy/Immunology/Infectious; Cardiovascular	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; The condition can involve structural and other cardiovascular anoamalies, and awareness may allow early diagnosis and management	Allergy/Immunology/Infectious; Cardiovascular	32181500; 32905580

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FNIP1 gene.

• not provided (193 variants)
• Inborn genetic diseases (40 variants)
• not specified (6 variants)
• Immunodeficiency 93 and hypertrophic cardiomyopathy (1 variants)
• FNIP1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FNIP1 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	51	10	62
missense			104	4	10	118
nonsense	2					2
start loss						0
frameshift	3					3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			2	7	1	10
non coding				16	7	23
Total	5	1	106	71	27

Variants in FNIP1

This is a list of pathogenic ClinVar variants found in the FNIP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-131644764-C-A			not provided (-)
5-131644771-A-G			Likely benign (Oct 13, 2023)
5-131644778-A-G			Likely benign (Nov 20, 2023)
5-131647075-A-G		not specified	Benign (Feb 01, 2024)
5-131647123-C-T			Uncertain significance (Aug 15, 2022)
5-131647131-C-A			Likely benign (Mar 21, 2022)
5-131647131-C-T			Likely benign (Mar 14, 2022)
5-131647159-C-T		Immunodeficiency 93 and hypertrophic cardiomyopathy	Pathogenic (Jan 24, 2022)
5-131647195-T-C		Inborn genetic diseases	Uncertain significance (May 08, 2023)
5-131647219-G-A			Likely benign (Jul 12, 2023)
5-131651785-G-A			Likely benign (Jan 12, 2024)
5-131651794-A-G			Uncertain significance (Jul 06, 2022)
5-131651801-C-T		Immunodeficiency 93 and hypertrophic cardiomyopathy	Pathogenic (Jan 24, 2022)
5-131651810-G-A			Uncertain significance (Jun 15, 2022)
5-131651819-T-C			Uncertain significance (Aug 06, 2022)
5-131651866-C-A			Uncertain significance (May 21, 2022)
5-131651876-A-G			Likely benign (Nov 28, 2023)
5-131651889-CA-C		Immunodeficiency 93 and hypertrophic cardiomyopathy	Pathogenic (Jan 24, 2022)
5-131651896-T-C		Inborn genetic diseases	Uncertain significance (Nov 09, 2022)
5-131651908-C-T		Inborn genetic diseases	Uncertain significance (Oct 06, 2022)
5-131651917-C-G		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
5-131651956-A-G			Uncertain significance (Sep 06, 2022)
5-131651973-T-C			Likely benign (Nov 03, 2022)
5-131652004-A-G			Likely benign (Apr 23, 2022)
5-131670389-A-G		not specified	Benign (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FNIP1	protein_coding	protein_coding	ENST00000510461	18	155304

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000426	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.35	449	613	0.733	0.0000312	7731
Missense in Polyphen		229	356.49	0.64237		4334
Synonymous	0.791	195	210	0.931	0.0000102	2156
Loss of Function	6.05	8	57.6	0.139	0.00000339	676

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000216	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000185	0.000185
European (Non-Finnish)	0.0000449	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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. Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways (PubMed:17028174). May regulate phosphorylation of RPS6KB1 (PubMed:18663353). {ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:27353360}.
• Pathway: mTOR signaling pathway - Homo sapiens (human) (Consensus)

Intolerance Scores

• loftool: 0.431
• rvis_EVS: -0.57
• rvis_percentile_EVS: 19.01

Haploinsufficiency Scores

• pHI: 0.563
• hipred: Y
• hipred_score: 0.749
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.867

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fnip1
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; renal/urinary system phenotype; liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic 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); neoplasm; immune system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of protein phosphorylation;positive regulation of protein phosphorylation;immature B cell differentiation;positive regulation of B cell apoptotic process;mitochondrion organization;cellular response to starvation;positive regulation of protein complex assembly;TOR signaling;negative regulation of TOR signaling;positive regulation of peptidyl-serine phosphorylation;TORC1 signaling;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;regulation of pro-B cell differentiation
• Cellular component: cytoplasm
• Molecular function: guanyl-nucleotide exchange factor activity;protein binding;ATPase inhibitor activity;chaperone binding