NFASC

neurofascin, the group of Fibronectin type III domain containing|I-set domain containing|Ig-like cell adhesion molecule family

Basic information

Region (hg38): 1:204828650-205022822

Links

ENSG00000163531 ∙ NCBI:23114 ∙ OMIM:609145 ∙ HGNC:29866 ∙ Uniprot:O94856 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with central and peripheral motor dysfunction (Limited), mode of inheritance: AD
• neurodevelopmental disorder with central and peripheral motor dysfunction (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with central and peripheral motor dysfunction (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with central and peripheral motor dysfunction	AR	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	Neurologic	28940097; 30124836; 30850329

ClinVar

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

• Inborn genetic diseases (59 variants)
• not provided (52 variants)
• Neurodevelopmental disorder with central and peripheral motor dysfunction (24 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFASC 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				11	10	21
missense			77	15		92
nonsense		1				1
start loss						0
frameshift	1					1
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			2	1		3
non coding			2		2	4
Total	1	1	81	26	12

Variants in NFASC

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

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

Position	Type	Phenotype	Significance	ClinVar
1-204926595-A-G		Neurodevelopmental disorder with central and peripheral motor dysfunction	Uncertain significance (May 14, 2020)
1-204939306-C-T		Neurodevelopmental disorder with central and peripheral motor dysfunction	Uncertain significance (Jul 29, 2023)
1-204944333-G-A			Likely benign (Jul 01, 2022)
1-204944335-C-T		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
1-204944337-C-T		Neurodevelopmental disorder with central and peripheral motor dysfunction • NFASC-related disorder	Conflicting classifications of pathogenicity (Jan 06, 2023)
1-204944382-G-A		Inborn genetic diseases	Uncertain significance (Jul 06, 2022)
1-204944400-A-G		Inborn genetic diseases	Likely benign (May 10, 2023)
1-204952058-G-A		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
1-204952115-A-G			Uncertain significance (Mar 30, 2023)
1-204952130-A-G		Neurodevelopmental disorder with central and peripheral motor dysfunction	Benign (Sep 05, 2021)
1-204954224-C-T			Likely benign (Oct 01, 2022)
1-204954235-C-T		Inborn genetic diseases	Uncertain significance (Nov 01, 2021)
1-204954283-G-A		Inborn genetic diseases	Uncertain significance (Jun 30, 2023)
1-204954297-C-A		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
1-204954304-A-G		Inborn genetic diseases	Uncertain significance (Jun 01, 2023)
1-204954348-A-G		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
1-204954349-C-T			Uncertain significance (Nov 30, 2022)
1-204954350-G-A			Likely benign (May 01, 2022)
1-204954834-C-T		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
1-204954892-C-T			Benign/Likely benign (Feb 01, 2024)
1-204954911-G-A		NFASC-related disorder	Benign (May 01, 2019)
1-204954942-A-G		Neurodevelopmental disorder with central and peripheral motor dysfunction	Uncertain significance (-)
1-204957652-A-G		NFASC-related disorder	Likely benign (Sep 18, 2019)
1-204957683-G-A		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
1-204957702-C-T			Likely benign (Jan 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFASC	protein_coding	protein_coding	ENST00000339876	28	194172

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000120	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	588	793	0.741	0.0000518	8068
Missense in Polyphen		194	331.88	0.58455		3432
Synonymous	0.216	328	333	0.985	0.0000246	2479
Loss of Function	6.69	8	67.1	0.119	0.00000380	691

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.000240	0.000198
East Asian	0.000109	0.000109
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.0000534	0.0000527
Middle Eastern	0.000109	0.000109
South Asian	0.0000341	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cell adhesion, ankyrin-binding protein which may be involved in neurite extension, axonal guidance, synaptogenesis, myelination and neuron-glial cell interactions. {ECO:0000250}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Developmental Biology;Neutrophil degranulation;Innate Immune System;Immune System;Neurofascin interactions;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.197

Intolerance Scores

• loftool: 0.529
• rvis_EVS: -1.8
• rvis_percentile_EVS: 2.21

Haploinsufficiency Scores

• pHI: 0.250
• hipred: Y
• hipred_score: 0.756
• ghis: 0.608

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.285

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nfasc
• Phenotype: homeostasis/metabolism 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); growth/size/body region 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: protein localization to paranode region of axon;axon guidance;peripheral nervous system development;transmission of nerve impulse;paranodal junction assembly;heterotypic cell-cell adhesion;myelination;neutrophil degranulation;clustering of voltage-gated sodium channels;synapse organization;protein localization to juxtaparanode region of axon;protein localization to plasma membrane
• Cellular component: plasma membrane;focal adhesion;integral component of membrane;dendrite;paranodal junction;node of Ranvier;paranode region of axon;axon initial segment;myelin sheath;Schwann cell microvillus;ficolin-1-rich granule membrane
• Molecular function: protein binding;protein domain specific binding;protein binding involved in heterotypic cell-cell adhesion