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 (1423 variants)
Charcot-Marie-Tooth_disease_dominant_intermediate_E (1399 variants)
not_provided (294 variants)
Inborn_genetic_diseases (270 variants)
not_specified (112 variants)
INF2-related_disorder (69 variants)
Focal_segmental_glomerulosclerosis (16 variants)
Charcot-Marie-Tooth_disease (16 variants)
Kidney_disorder (15 variants)
Nephrotic_syndrome (3 variants)
Corticosteroids_response (2 variants)
Proteinuria (2 variants)
Glomerulonephritis (1 variants)
Neuropathy,_hereditary_motor_and_sensory,_type_6B (1 variants)
Mixed_demyelinating_and_axonal_polyneuropathy (1 variants)
Small_for_gestational_age (1 variants)
Chronic_kidney_disease (1 variants)
Oligohydramnios (1 variants)
Interosseus_muscle_atrophy (1 variants)
Periodic_fever_syndrome (1 variants)
Renal_insufficiency (1 variants)
Birth_length_less_than_3rd_percentile (1 variants)
Progressive_pes_cavus (1 variants)
Hypertensive_disorder (1 variants)
Glomerulopathy_with_fibronectin_deposits_2 (1 variants)
Premature_birth (1 variants)
Motor_polyneuropathy (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. These statistics are base on transcript: NM_000022489.4. 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			15 clinvar	393 clinvar	25 clinvar	433
missense	17 clinvar	35 clinvar	503 clinvar	234 clinvar	19 clinvar	808
nonsense			10 clinvar			10
start loss						0
frameshift		1 clinvar	24 clinvar	2 clinvar		27
splice donor/acceptor (+/-2bp)		1 clinvar	7 clinvar			8
Total	17	37	559	629	44

Highest pathogenic variant AF is 0.00000410693

Loading clinvar variants...

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

pHI
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