NFIB

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

Basic information

Region (hg38): 9:14081842-14398983

Links

ENSG00000147862 ∙ NCBI:4781 ∙ OMIM:600728 ∙ HGNC:7785 ∙ Uniprot:O00712 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• macrocephaly, acquired, with impaired intellectual development (Moderate), mode of inheritance: AD
• macrocephaly, acquired, with impaired intellectual development (Strong), mode of inheritance: AD
• macrocephaly, acquired, with impaired intellectual development (Strong), mode of inheritance: AD
• macrocephaly, acquired, with impaired intellectual development (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macrocephaly, acquired, with impaired intellectual development	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	30388402

ClinVar

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

• not provided (35 variants)
• Macrocephaly, acquired, with impaired intellectual development (33 variants)
• Inborn genetic diseases (11 variants)
• Macrocephaly;Intellectual disability (8 variants)
• NFIB-related condition (2 variants)
• not specified (2 variants)
• Autism spectrum disorder (2 variants)
• Marfanoid habitus and intellectual disability (1 variants)
• Neurodevelopmental disorder (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFIB 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				4		4
missense	1	5	34	5		45
nonsense	4	3	1			8
start loss			1			1
frameshift	4	5	2			11
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1		2			3
splice region			2	2		4
non coding			3	1	1	5
Total	10	13	44	10	1

Variants in NFIB

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

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

Position	Type	Phenotype	Significance	ClinVar
9-14088120-T-A			Likely benign (Dec 01, 2023)
9-14088211-C-G		Macrocephaly, acquired, with impaired intellectual development	Uncertain significance (Apr 24, 2020)
9-14088248-G-A		NFIB-related disorder	Likely benign (Mar 02, 2023)
9-14113001-G-A		Macrocephaly, acquired, with impaired intellectual development	Likely pathogenic (Mar 26, 2024)
9-14113018-G-T		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
9-14113043-C-T		NFIB-related disorder	Uncertain significance (Jul 11, 2023)
9-14113076-T-C		Inborn genetic diseases	Uncertain significance (Jan 31, 2024)
9-14116247-T-G		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
9-14116262-G-A			Uncertain significance (Feb 13, 2019)
9-14116300-G-C		NFIB-related disorder • Inborn genetic diseases	Likely benign (Dec 14, 2023)
9-14116313-G-A		Inborn genetic diseases	Uncertain significance (Feb 09, 2024)
9-14116328-C-G		NFIB-related disorder	Benign/Likely benign (Apr 01, 2024)
9-14120468-T-C		Macrocephaly, acquired, with impaired intellectual development	Uncertain significance (Jan 21, 2021)
9-14120480-T-C		Inborn genetic diseases	Uncertain significance (May 01, 2022)
9-14120502-G-C			Uncertain significance (Oct 25, 2022)
9-14120538-A-G		Macrocephaly, acquired, with impaired intellectual development	Uncertain significance (Mar 09, 2020)
9-14120548-C-T			Likely benign (Dec 01, 2023)
9-14120549-G-C		Macrocephaly, acquired, with impaired intellectual development	Uncertain significance (Jan 14, 2021)
9-14120554-G-A			Likely benign (Jun 18, 2018)
9-14120564-A-G			Uncertain significance (May 03, 2019)
9-14120567-A-C		not specified	Uncertain significance (Mar 28, 2023)
9-14120598-G-A		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
9-14120608-AGTTCGAGTTGAGAT-A		Macrocephaly;Intellectual disability • Macrocephaly, acquired, with impaired intellectual development	Pathogenic (-)
9-14120611-TC-T		Macrocephaly, acquired, with impaired intellectual development	Pathogenic (Apr 05, 2022)
9-14120618-G-A		Macrocephaly;Intellectual disability	Uncertain significance (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFIB	protein_coding	protein_coding	ENST00000380953	11	317141

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00139	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.47	151	264	0.572	0.0000139	3206
Missense in Polyphen		64	154.58	0.41402		1886
Synonymous	-1.38	114	96.7	1.18	0.00000530	990
Loss of Function	4.55	2	27.9	0.0716	0.00000174	294

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.
• Pathway: Pathways Affected in Adenoid Cystic Carcinoma;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: 0.419

Intolerance Scores

• loftool: 0.0759
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24

Haploinsufficiency Scores

• pHI: 0.945
• hipred: Y
• hipred_score: 0.808
• ghis: 0.626

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.811

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nfib
• Phenotype: respiratory 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); vision/eye phenotype; digestive/alimentary 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); homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chondrocyte differentiation;DNA replication;response to bacterium;glial cell differentiation;principal sensory nucleus of trigeminal nerve development;anterior commissure morphogenesis;hindbrain development;positive regulation of transcription by RNA polymerase II;Clara cell differentiation;type I pneumocyte differentiation;type II pneumocyte differentiation;salivary gland cavitation;cell differentiation involved in salivary gland development;lung ciliated cell differentiation;commissural neuron axon guidance;negative regulation of pri-miRNA transcription by RNA polymerase II;negative regulation of mesenchymal cell proliferation involved in lung development;negative regulation of epithelial cell proliferation involved in lung morphogenesis
• Cellular component: fibrillar center;nucleus;cerebellar mossy fiber
• 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;DNA binding