INF2

inverted formin 2, the group of Formins|Armadillo like helical domain containing

Basic information

Region (hg38): 14:104681146-104722535

Previous symbols: [ "C14orf151", "C14orf173" ]

Links

ENSG00000203485 ∙ NCBI:64423 ∙ OMIM:610982 ∙ HGNC:23791 ∙ Uniprot:Q27J81 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease dominant intermediate E (Supportive), mode of inheritance: AD
• focal segmental glomerulosclerosis 5 (Strong), mode of inheritance: AD
• Charcot-Marie-Tooth disease dominant intermediate E (Strong), mode of inheritance: AD
• Charcot-Marie-Tooth disease dominant intermediate E (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Focal segmental glomerulosclerosis 5	AD	Renal	The condition can involve renal failure, and early diagnosis may enable management considerations	Neurologic; Renal	20023659; 21415313; 22187985; 22961558; 22971997

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the INF2 gene.

• Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E (6 variants)
• Charcot-Marie-Tooth disease (5 variants)
• Focal segmental glomerulosclerosis 5 (4 variants)
• Charcot-Marie-Tooth disease dominant intermediate E;Focal segmental glomerulosclerosis 5 (4 variants)
• Charcot-Marie-Tooth disease dominant intermediate E (2 variants)
• not provided (2 variants)
• INF2-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the INF2 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			10	333	26	369
missense	11	20	390	106	21	548
nonsense			8			8
start loss						0
frameshift		1	18			19
inframe indel	1	1	22	1	1	26
splice donor/acceptor (+/-2bp)		1	4			5
splice region			24	52	2	78
non coding			18	172	70	260
Total	12	23	470	612	118

Variants in INF2

This is a list of pathogenic ClinVar variants found in the INF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-104689661-G-C		Focal segmental glomerulosclerosis 5	Uncertain significance (Jan 12, 2018)
14-104689664-G-A		Focal segmental glomerulosclerosis 5	Benign (Sep 16, 2020)
14-104689699-G-A		Focal segmental glomerulosclerosis 5	Uncertain significance (Jan 13, 2018)
14-104689739-G-A		Focal segmental glomerulosclerosis 5 • not specified • Charcot-Marie-Tooth disease dominant intermediate E	Conflicting classifications of pathogenicity (Mar 20, 2019)
14-104689739-G-C		not specified	Likely benign (Apr 14, 2016)
14-104689755-C-A			Likely benign (May 08, 2018)
14-104689843-G-A			Likely benign (Jan 20, 2021)
14-104699583-G-A			Likely benign (Aug 01, 2024)
14-104701055-C-G			Likely benign (Aug 06, 2019)
14-104701117-G-T			Likely benign (Oct 09, 2019)
14-104701320-C-T			Benign (Jul 09, 2020)
14-104701371-G-A		Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E	Benign (Oct 23, 2022)
14-104701378-G-A		Focal segmental glomerulosclerosis 5	Uncertain significance (Aug 09, 2024)
14-104701379-A-T		Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E	Uncertain significance (Nov 14, 2023)
14-104701382-G-T		Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E	Uncertain significance (May 09, 2023)
14-104701383-C-T		Charcot-Marie-Tooth disease dominant intermediate E;Focal segmental glomerulosclerosis 5 • Focal segmental glomerulosclerosis 5	Conflicting classifications of pathogenicity (Apr 22, 2023)
14-104701385-C-T		Inborn genetic diseases	Uncertain significance (Nov 13, 2020)
14-104701390-C-A			Uncertain significance (Jul 02, 2020)
14-104701391-G-C		Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E	Uncertain significance (Mar 31, 2022)
14-104701391-G-T		Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E	Likely benign (Nov 22, 2023)
14-104701399-G-A		Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E	Uncertain significance (Sep 23, 2022)
14-104701402-G-A		Focal segmental glomerulosclerosis 5 • Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E • Inborn genetic diseases • INF2-related disorder	Benign/Likely benign (Jan 24, 2024)
14-104701407-G-A		not specified • Focal segmental glomerulosclerosis 5 • Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E • Focal segmental glomerulosclerosis	Benign (Feb 01, 2024)
14-104701416-G-A		Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E	Likely benign (Jan 12, 2023)
14-104701419-G-A		Focal segmental glomerulosclerosis 5;Charcot-Marie-Tooth disease dominant intermediate E	Likely benign (Oct 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
INF2	protein_coding	protein_coding	ENST00000392634	21	30000

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.973	0.0265	124713	0	57	124770	0.000228

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.31	581	760	0.764	0.0000515	7893
Missense in Polyphen		75	159.9	0.46904		1675
Synonymous	-0.457	375	364	1.03	0.0000276	2660
Loss of Function	5.64	10	55.3	0.181	0.00000300	578

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000603	0.000603
Ashkenazi Jewish	0.00	0.00
East Asian	0.000668	0.000668
Finnish	0.000141	0.000139
European (Non-Finnish)	0.000205	0.000203
Middle Eastern	0.000668	0.000668
South Asian	0.0000654	0.0000654
Other	0.000496	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Severs actin filaments and accelerates their polymerization and depolymerization. {ECO:0000250}.
• Disease: DISEASE: Focal segmental glomerulosclerosis 5 (FSGS5) [MIM:613237]: A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. {ECO:0000269|PubMed:20023659, ECO:0000269|PubMed:21258034, ECO:0000269|PubMed:21866090, ECO:0000269|PubMed:22971997, ECO:0000269|PubMed:23014460, ECO:0000269|PubMed:25165188}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, dominant, intermediate type, E (CMTDIE) [MIM:614455]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type E is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. Patients additionally manifest focal segmental glomerulonephritis, proteinuria, progression to end- stage renal disease, and a characteristic histologic pattern on renal biopsy. {ECO:0000269|PubMed:22187985, ECO:0000269|PubMed:24174593, ECO:0000269|PubMed:24750328, ECO:0000269|PubMed:25165188, ECO:0000269|PubMed:25676889}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Primary Focal Segmental Glomerulosclerosis FSGS (Consensus)

Intolerance Scores

• loftool: 0.0417
• rvis_EVS: -0.03
• rvis_percentile_EVS: 50.56

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.662
• ghis: 0.508

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.252

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Inf2
• 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); reproductive system phenotype; embryo phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: inf2
• Affected structure: glomerular basement membrane
• Phenotype tag: abnormal
• Phenotype quality: increased permeability

Gene ontology

• Biological process: actin cytoskeleton organization;regulation of mitochondrial fission
• Cellular component: perinuclear region of cytoplasm
• Molecular function: actin binding;Rho GTPase binding