NCDN

neurochondrin, the group of Armadillo like helical domain containing

Basic information

Region (hg38): 1:35557473-35567274

Links

ENSG00000020129 ∙ NCBI:23154 ∙ OMIM:608458 ∙ HGNC:17597 ∙ Uniprot:Q9UBB6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• neurodevelopmental disorder with infantile epileptic spasms (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with infantile epileptic spasms	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; Musculoskeletal; Neurologic	33711248

ClinVar

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

• Neurodevelopmental disorder with infantile epileptic spasms (3 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCDN 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				12	1	13
missense	3	2	53	3		61
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				1		1
non coding						0
Total	3	3	54	15	1

Variants in NCDN

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

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

Position	Type	Phenotype	Significance	ClinVar
1-35559147-C-T		not specified	Uncertain significance (Jan 16, 2024)
1-35559188-T-C		not specified	Uncertain significance (Oct 09, 2024)
1-35559200-C-T		Neurodevelopmental disorder with infantile epileptic spasms	Uncertain significance (Jul 20, 2022)
1-35560322-A-G		NCDN-related disorder	Likely benign (Sep 01, 2022)
1-35560353-A-C			Uncertain significance (Aug 16, 2023)
1-35560364-A-T		NCDN-related disorder	Uncertain significance (Sep 25, 2024)
1-35560366-C-CT		Neurodevelopmental disorder with infantile epileptic spasms	Likely pathogenic (-)
1-35560368-C-T		Floating-Harbor syndrome • Neurodevelopmental disorder with infantile epileptic spasms	Uncertain significance (Jul 09, 2024)
1-35560376-G-T			Likely benign (Nov 01, 2024)
1-35560391-C-T			Likely benign (Jun 01, 2022)
1-35560410-C-A		Neurodevelopmental disorder with infantile epileptic spasms	Uncertain significance (Jan 03, 2022)
1-35560421-C-A			Likely benign (Jan 01, 2023)
1-35560451-C-G		not specified	Uncertain significance (Aug 05, 2024)
1-35560462-G-A		not specified	Uncertain significance (Jun 01, 2023)
1-35560470-G-A			Uncertain significance (Dec 01, 2024)
1-35560514-C-T			Likely benign (Mar 01, 2024)
1-35560515-G-A		not specified	Uncertain significance (Mar 06, 2025)
1-35560566-G-A		not specified	Uncertain significance (Aug 20, 2024)
1-35560569-C-T		not specified	Uncertain significance (Feb 06, 2024)
1-35560570-G-A		not specified	Uncertain significance (Jul 12, 2022)
1-35560570-G-C			Uncertain significance (Mar 25, 2023)
1-35560577-C-A		not specified	Uncertain significance (Sep 22, 2023)
1-35560593-C-T		not specified	Uncertain significance (Feb 23, 2023)
1-35560641-G-A		Neurodevelopmental disorder with infantile epileptic spasms • not specified	Uncertain significance (May 17, 2023)
1-35560716-G-A		not specified • NCDN-related disorder • Neurodevelopmental disorder with infantile epileptic spasms	Uncertain significance (Dec 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCDN	protein_coding	protein_coding	ENST00000373243	7	9802

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000364	125715	0	5	125720	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.76	235	463	0.508	0.0000303	4608
Missense in Polyphen		35	121.62	0.28779		1273
Synonymous	0.732	203	217	0.937	0.0000148	1647
Loss of Function	4.65	1	27.1	0.0369	0.00000134	281

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)	0.0000792	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably involved in signal transduction, in the nervous system, via increasing cell surface localization of GRM5 and positively regulating its signaling (By similarity). Required for the spatial learning process. Acts as a negative regulator of Ca(2+)-calmodulin-dependent protein kinase 2 (CaMK2) phosphorylation. May play a role in modulating melanin- concentrating hormone-mediated functions via its interaction with MCHR1 that interferes with G protein-coupled signal transduction. May be involved in bone metabolism. May also be involved in neurite outgrowth. {ECO:0000250, ECO:0000269|PubMed:16945926}.
• Pathway: Splicing factor NOVA regulated synaptic proteins (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.0479
• rvis_EVS: -0.98
• rvis_percentile_EVS: 8.75

Haploinsufficiency Scores

• pHI: 0.419
• hipred: Y
• hipred_score: 0.686
• ghis: 0.664

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ncdn
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo 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; 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); skeleton phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: neuron projection development;bone resorption;regulation of neuronal synaptic plasticity
• Cellular component: nucleus;cytosol;membrane;axon;dendrite;neuronal cell body
• Molecular function: protein binding