NFIA

nuclear factor I A, the group of Nuclear factor I family

Basic information

Region (hg38): 1:60865259-61462788

Links

ENSG00000162599 ∙ NCBI:4774 ∙ OMIM:600727 ∙ HGNC:7784 ∙ Uniprot:Q12857 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• chromosome 1p32-p31 deletion syndrome (Strong), mode of inheritance: AD
• brain malformations with or without urinary tract defects (Strong), mode of inheritance: AD
• chromosome 1p32-p31 deletion syndrome (Definitive), mode of inheritance: AD
• brain malformations with or without urinary tract defects (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brain malformations with or without urinary tract defects	AD	Renal	The condition can include renal anomalies such as hydronephrosis and vesicoureteral reflux and awareness may allow early management, which may help prevent or manage renal sequelae	Neurologic; Renal	17530927; 24462883; 27081522

ClinVar

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

• not_provided (246 variants)
• Inborn_genetic_diseases (39 variants)
• Brain_malformations_with_or_without_urinary_tract_defects (31 variants)
• NFIA-related_disorder (21 variants)
• Chromosome_1p32-p31_deletion_syndrome (14 variants)
• not_specified (5 variants)
• Neurodevelopmental_disorder (1 variants)
• Cleft_palate (1 variants)
• Intellectual_disability (1 variants)
• Macrocephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFIA gene is commonly pathogenic or not. These statistics are base on transcript: NM_001134673.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				62		62
missense	2	7	100	7		116
nonsense	10	10	1			21
start loss	1	1	1			3
frameshift	11	18				29
splice donor/acceptor (+/-2bp)	3		1			4
Total	27	36	103	69	0

Highest pathogenic variant AF is 0.0000013681388

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFIA	protein_coding	protein_coding	ENST00000371189	12	597535

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000407	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.23	158	321	0.492	0.0000181	3571
Missense in Polyphen		44	137.52	0.31996		1539
Synonymous	-0.114	123	121	1.01	0.00000697	1123
Loss of Function	4.85	2	31.2	0.0640	0.00000202	323

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Recognizes and binds the palindromic sequence 5'- TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.
• Disease: DISEASE: Brain malformations with or without urinary tract defects (BRMUTD) [MIM:613735]: A syndrome characterized by corpus callosum hypoplasia or agenesis, hydrocephalus or ventricular enlargement, developmental delay, and urinary tract defects. {ECO:0000269|PubMed:24462883, ECO:0000269|PubMed:27081522}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Gene expression (Transcription);RNA Polymerase III Transcription Termination;FOXA1 transcription factor network;RNA Polymerase III Abortive And Retractive Initiation;RNA Polymerase III Transcription (Consensus)

Recessive Scores

• pRec: 0.361

Intolerance Scores

• loftool: 0.0782
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

• pHI: 0.350
• hipred: Y
• hipred_score: 0.773
• ghis: 0.614

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.563

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nfia
• Phenotype: growth/size/body region phenotype; cellular phenotype; craniofacial phenotype; reproductive 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;DNA replication;regulation of transcription, DNA-templated;viral genome replication;positive regulation of transcription by RNA polymerase II;synapse maturation;ureter development
• Cellular component: nucleus;nucleoplasm;cell junction
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;transcription factor binding